CA2530619C - Non-gelatin film and method and apparatus for producing same - Google Patents
Non-gelatin film and method and apparatus for producing same Download PDFInfo
- Publication number
- CA2530619C CA2530619C CA2530619A CA2530619A CA2530619C CA 2530619 C CA2530619 C CA 2530619C CA 2530619 A CA2530619 A CA 2530619A CA 2530619 A CA2530619 A CA 2530619A CA 2530619 C CA2530619 C CA 2530619C
- Authority
- CA
- Canada
- Prior art keywords
- film
- forming composition
- water
- carrageenan
- percent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 0 *CC*1CCCCC1 Chemical compound *CC*1CCCCC1 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4891—Coated capsules; Multilayered drug free capsule shells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
Abstract
A film-forming composition comprising a hydrocolloid, a plasticizer, and water is described. A process and apparatus for producing a non-gelatin film comprising a hydrocolloid, a plasticizer, and water is also disclosed. The process includes combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition comprising at least about 40 percent water by weight. A
substantial portion of the water is then extracted from the film-forming composition to form a dried portion having a water content of less than or equal to about 25 percent by weight. The dried portion of the film-forming composition is formed into a film. A film produced according to the process preferably has a tensile strength at rupture of at least about 5 N, and a percent elongation of at least about 50 percent at rupture at room temperature. An apparatus for performing the process is also described, as well oral dosage forms encapsulated or enrobed in the produced film.
substantial portion of the water is then extracted from the film-forming composition to form a dried portion having a water content of less than or equal to about 25 percent by weight. The dried portion of the film-forming composition is formed into a film. A film produced according to the process preferably has a tensile strength at rupture of at least about 5 N, and a percent elongation of at least about 50 percent at rupture at room temperature. An apparatus for performing the process is also described, as well oral dosage forms encapsulated or enrobed in the produced film.
Description
NON-GELATIN FILM AND
METHOD AND APPARATUS FOR PRODUCING SAME
Related Applications This application is a continuation-in-part of Application Serial No.
10/051,201, filed January 1 ~, 2U02.
Field of the invention The present invention relates to the field of film-forming or gel-forming compositions, and more particularly to substitutes for mammalian-based gel forming materials used in the manufacture of softgels and gelcaps, and a method and apparatus for producing a non-animal edible film of a type that is suitable for enrobing and/or encapsulating oral dosage forms.
Bacl~ground Gelatin has a wide xange of commercial utility. For example, gelatin is used in wet processed photographic emulsions, pharmaceutical dosage forms, cosmetics (binder), arid a wide range of food products. ('gelatin has many useful physical and chemical properties that support this broad range of utility.
Gelatin is manufactured by the hydrolysis of animal by-products that contain collagen. This is usually found in animal bones, skins, and connective tissue.
'The collagen containing material is heated in water and the liquor produced is concentrated and dried, leaving behind the colorless or pale yellow protein that constitutes the hydrophilic c~Iloid material known as gelatin.
The primary sources of gelatin are from bovine and swine animals.
Additionally, i~sh grad poa.~ltry are alternative small volume sources of gelatin. The source of gelatin can be a problem for potential areas of use car for paa'ticular cr~ns~a~~dc~r~.
l~~rgo gx~aup~ ~roun~x the world choose raot to ingest any products of pigs (e.g., vegetarians I-lebre~vs, and Muslims) ~r the products ~f beef (e.g., vegetariabas and I~ind~as). ~s medication andlor diet ~0 supplements are provided in gelatin capsules v~ithout any indicati~n ~f the s~o~arce of the gelatin, the use of capsules is restricted in areas where religious beliefs question the source of the gelatin. Additionally, due to reported possibilities of cross-contamination of diseases among species, for example bovine spongiform encephalopathy ("13SE"
or "Mad t_;ow iW sease"), the use of uncontrolled by-products from animals has lost some.~cvel of commercial acceptance. In short, there is a need for replacement compositions for gelatin that are not derived from animal sources.
Gelatin is a protein hydrocolloid. Hydrocolloids are hydrophilic colloidal materials that readily absorb water. Types of non-gelatin hydrocolloids include plant exudates, seaweed extracts, plant seed gums or mucilages, cereal gums, fermentation gums, modified cellulose, and modified starches. Non-gelatin hydrocolloids suitable for inclusion in a film-forming composition according to the invention include, but are not limited to, carrageenan, alginates, agar, guar, pectin, locust bean gum, xanthan gum, unmodified starch, modified pregelatinized starch, and gellan gum. Carrageenan is particularly useful in producing a non-gelatin film according to the invention.
Carrageenan is a natural polysaccharide hydrocolloid derived from red seaweed of the species Rhodophycea. Carrageenan is a carbohydrate polymer of repeating galactose and 3,6-anhydrogalactose (sugar) units that is linear and withaut significant numbers of branches or substitutions. Most, if not all, of the galactose units on a carrageenan molecule possess a sulfated ester group. The exact position of the sulfate groups, the rattans on the sulfate groups, and the possible presence of an anhydrous bridge on the molecule differentiate the various types of carrageenan.
There are five distinct types of carragecnan, each of which behaves differently and has distinct properties. The types of carrageenan are iota, kappa, lambda, mu and nu carrageenan. These types of carrageenan can significantly vary in properties.
For example, lambda carrageenan in solution is unable to associate into a structure, and therefore is unable to farm a gel, but nonetheless acts as a thickener. Both kappa and iota carrageenan, the predoaninant carrageenan types, are capable of forming gels.
Kappa carrageenan is l~nown to form strong gels in the presence of potassium rations. However, lc~pp~ carr~r~gr~~~~a~rb gels Lead to L~e brittle aa~d ea~laibit s~sneresi~
(ea~udation of the liquid portion of the gel). Iata carrageenan tends to react str~ngly to calcium raft~ns and foams a vrealcer and more fle~~ible gel than l~a~ppa carrageenan. Iota carrageenan is nat: as susceptible to syneresis as kappa carrageenan. i~a and nu carrageenan are thought to be precursors of kappa carrageenan and iota carrageenan, respectively' and may be present only in very small quantities as impurities in pure kappa and iota carrageenan. lulu and nu carrageenan are not of commercial importance.
METHOD AND APPARATUS FOR PRODUCING SAME
Related Applications This application is a continuation-in-part of Application Serial No.
10/051,201, filed January 1 ~, 2U02.
Field of the invention The present invention relates to the field of film-forming or gel-forming compositions, and more particularly to substitutes for mammalian-based gel forming materials used in the manufacture of softgels and gelcaps, and a method and apparatus for producing a non-animal edible film of a type that is suitable for enrobing and/or encapsulating oral dosage forms.
Bacl~ground Gelatin has a wide xange of commercial utility. For example, gelatin is used in wet processed photographic emulsions, pharmaceutical dosage forms, cosmetics (binder), arid a wide range of food products. ('gelatin has many useful physical and chemical properties that support this broad range of utility.
Gelatin is manufactured by the hydrolysis of animal by-products that contain collagen. This is usually found in animal bones, skins, and connective tissue.
'The collagen containing material is heated in water and the liquor produced is concentrated and dried, leaving behind the colorless or pale yellow protein that constitutes the hydrophilic c~Iloid material known as gelatin.
The primary sources of gelatin are from bovine and swine animals.
Additionally, i~sh grad poa.~ltry are alternative small volume sources of gelatin. The source of gelatin can be a problem for potential areas of use car for paa'ticular cr~ns~a~~dc~r~.
l~~rgo gx~aup~ ~roun~x the world choose raot to ingest any products of pigs (e.g., vegetarians I-lebre~vs, and Muslims) ~r the products ~f beef (e.g., vegetariabas and I~ind~as). ~s medication andlor diet ~0 supplements are provided in gelatin capsules v~ithout any indicati~n ~f the s~o~arce of the gelatin, the use of capsules is restricted in areas where religious beliefs question the source of the gelatin. Additionally, due to reported possibilities of cross-contamination of diseases among species, for example bovine spongiform encephalopathy ("13SE"
or "Mad t_;ow iW sease"), the use of uncontrolled by-products from animals has lost some.~cvel of commercial acceptance. In short, there is a need for replacement compositions for gelatin that are not derived from animal sources.
Gelatin is a protein hydrocolloid. Hydrocolloids are hydrophilic colloidal materials that readily absorb water. Types of non-gelatin hydrocolloids include plant exudates, seaweed extracts, plant seed gums or mucilages, cereal gums, fermentation gums, modified cellulose, and modified starches. Non-gelatin hydrocolloids suitable for inclusion in a film-forming composition according to the invention include, but are not limited to, carrageenan, alginates, agar, guar, pectin, locust bean gum, xanthan gum, unmodified starch, modified pregelatinized starch, and gellan gum. Carrageenan is particularly useful in producing a non-gelatin film according to the invention.
Carrageenan is a natural polysaccharide hydrocolloid derived from red seaweed of the species Rhodophycea. Carrageenan is a carbohydrate polymer of repeating galactose and 3,6-anhydrogalactose (sugar) units that is linear and withaut significant numbers of branches or substitutions. Most, if not all, of the galactose units on a carrageenan molecule possess a sulfated ester group. The exact position of the sulfate groups, the rattans on the sulfate groups, and the possible presence of an anhydrous bridge on the molecule differentiate the various types of carrageenan.
There are five distinct types of carragecnan, each of which behaves differently and has distinct properties. The types of carrageenan are iota, kappa, lambda, mu and nu carrageenan. These types of carrageenan can significantly vary in properties.
For example, lambda carrageenan in solution is unable to associate into a structure, and therefore is unable to farm a gel, but nonetheless acts as a thickener. Both kappa and iota carrageenan, the predoaninant carrageenan types, are capable of forming gels.
Kappa carrageenan is l~nown to form strong gels in the presence of potassium rations. However, lc~pp~ carr~r~gr~~~~a~rb gels Lead to L~e brittle aa~d ea~laibit s~sneresi~
(ea~udation of the liquid portion of the gel). Iata carrageenan tends to react str~ngly to calcium raft~ns and foams a vrealcer and more fle~~ible gel than l~a~ppa carrageenan. Iota carrageenan is nat: as susceptible to syneresis as kappa carrageenan. i~a and nu carrageenan are thought to be precursors of kappa carrageenan and iota carrageenan, respectively' and may be present only in very small quantities as impurities in pure kappa and iota carrageenan. lulu and nu carrageenan are not of commercial importance.
2 t he type of carrageenan used affects the physical properties of the final gel or film.
WO 99/07347 and WO 01/03677 describe gel forming compositions that have iota carrageenan as the sole gelling agent. Despite the fact that kappa carrageenan is also able to gel, these publications teach that kappa carrageenan is detrimental when the end product desired is a f lm for capsule manufacture The phenomenon of syneresis and the fact that kappa carrageenan forms brittle gels are cited as reasons for avoiding the use of kappa carrageenan in such films.
When forming a film for subsequent use in medicinal, cosmetic, or nutritional capsule manufacture, the resultant physical properties of sealability, extensibility, and tensile strength are important. Thus, a gelling composition comprising carrageenan or other non-gelatin hydrocolloids must provide adequate physical properties useful in manufacturing. Kappa carrageenan is a less expensive starting material as compared to iota carrageenan. 'Thus, it would be beneficial to develop a gel- or film-forming composition comprising kappa carrageenan and iota carrageenan, wherein the resultant 1S film provides the requisite physical properties for capsule manufacture.
Processes to manufacture capsules from carrageenan and starch-based shell materials have been very limited. By nature, commercial powder forms of carrageenans and other hydrocolloids require a large percentage of water t~ fully hydrate.
ZTnfortunately, the strength of a film made from these materials at a water content necessary to fully hydrate the hydrocolloids is not as strong as desired for use in established enrobement and encapsulation processes. To facilitate producti~n of edible films in a production environment, it is sometimes beneficial to add additional amounts of water to a film-forming formula than is strictly required to hydrate the hyrdrocolloids.
This additional water reduces the viscosity of the mixture, thereby permitting the mixture to flow under gravity for subsequent processing. Unfortunately, this high water content v,ub~~~anl:ialh~ r~d~~ces tlae ~~trengtlx of f lna~ prodaaced f~oax~ saach the rnia~t.~are.
~ne method of producing non-gelatin films includes casting these materials at high ~,vater content into a, film then drying tIm film prior to use for encaps~ala~tion.
Unfortunately, such processes are less tlgala optirraal due to the long bane that is required to dry the f lms to a usable level for encapsulation. For this reason, production quantities of capsules have not been made using such a process. ~ther methods for producing non-gelatin films do not include a drying step prior to encapsulation. Instead, high volumes of
WO 99/07347 and WO 01/03677 describe gel forming compositions that have iota carrageenan as the sole gelling agent. Despite the fact that kappa carrageenan is also able to gel, these publications teach that kappa carrageenan is detrimental when the end product desired is a f lm for capsule manufacture The phenomenon of syneresis and the fact that kappa carrageenan forms brittle gels are cited as reasons for avoiding the use of kappa carrageenan in such films.
When forming a film for subsequent use in medicinal, cosmetic, or nutritional capsule manufacture, the resultant physical properties of sealability, extensibility, and tensile strength are important. Thus, a gelling composition comprising carrageenan or other non-gelatin hydrocolloids must provide adequate physical properties useful in manufacturing. Kappa carrageenan is a less expensive starting material as compared to iota carrageenan. 'Thus, it would be beneficial to develop a gel- or film-forming composition comprising kappa carrageenan and iota carrageenan, wherein the resultant 1S film provides the requisite physical properties for capsule manufacture.
Processes to manufacture capsules from carrageenan and starch-based shell materials have been very limited. By nature, commercial powder forms of carrageenans and other hydrocolloids require a large percentage of water t~ fully hydrate.
ZTnfortunately, the strength of a film made from these materials at a water content necessary to fully hydrate the hydrocolloids is not as strong as desired for use in established enrobement and encapsulation processes. To facilitate producti~n of edible films in a production environment, it is sometimes beneficial to add additional amounts of water to a film-forming formula than is strictly required to hydrate the hyrdrocolloids.
This additional water reduces the viscosity of the mixture, thereby permitting the mixture to flow under gravity for subsequent processing. Unfortunately, this high water content v,ub~~~anl:ialh~ r~d~~ces tlae ~~trengtlx of f lna~ prodaaced f~oax~ saach the rnia~t.~are.
~ne method of producing non-gelatin films includes casting these materials at high ~,vater content into a, film then drying tIm film prior to use for encaps~ala~tion.
Unfortunately, such processes are less tlgala optirraal due to the long bane that is required to dry the f lms to a usable level for encapsulation. For this reason, production quantities of capsules have not been made using such a process. ~ther methods for producing non-gelatin films do not include a drying step prior to encapsulation. Instead, high volumes of
3 carrageenan ~approx~maieiy 1 a io) are uses to achieve the strength requireet for capsule manufacture. Such high quantities of carrageenan are undesirable, however, due to the high cost of the material. Such a process also limits the variations in film formula that axe available to produce capsules with specific properties such as hardness. Such a process also include a melt on demand system that utilizes a pressurized system to help move the film material to a transfer pump to be processed. This pressurized system is necessary because the high quantity of carrageenan used in the film foxmula gives the mass a very high viscosity. The pressurized process is also necessary because the gel temperature of the film-forming material at high concentrations of carrageenan necessarily is very high.
Unfortunately, holding the mass at this high temperature for an extended period of time as is typically required for production encapsulation causes an undesirable breakdown of the hydrocolloids in the film-forming mixture.
Accordingly, there is a need for a process that permits the use of a variety of types arid concentrations of hydrocolloids and permits the viscosity of a film-forming composition to be sufficiently low such that the composition can flow under gravity. It is also desirable to have a process for producing films comprising many types of hydrocolloids that permits a film-forming composition comprising such hydrocolloids to be processed at temperatures that do not cause substantial degradation of the film-forming materials.
Summaay ~f the fuventi0n The present invention includes a method of producing a non-gelatin film. The method includes combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition comprising at least about 40 percent water by weight. The method farther includes extracting a portion of the ~~~~ter from the fll~rxa-fc~a~~ia~g; cotral-~~si~:iob~ to foa~~~ ~ dried portion having a water conEent ~f less than or equal to about 2~ percent by vreight. °The method als~
includes forming the dried portion of tlm film-~°~arming coanposition into a lalm.
°fhe invention also includes a method of producing a non-gelatin falm that includes combining apt least one non-gelatin hydrocolloid , water, and at least one plasticizer into ~
substantially homogeneous film-forming composition having a water content of at least about 40 percent by weight. This method further includes extracting a portion of the water q.
from the film-forming composition to form a dried portion, and forming the dried portion of the film-forming composition into a film. The film produced by such a method has a tensile strength at rupture of at least about 5 N at room temperature.
The invention further includes a method of producing a non-gelatin film including combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition comprising at least about 40 percent water by weight. A portion of the water is extracted from the film-forming composition to form a dried portion, and the dried portion of the film-forming composition is formed into a film having a percent elongation of at Ieast about 50 percent at rupture at room temperature.
In addition, the invention includes a method of producing a non-gelatin film including combining at least one non-gelatin hydrocolloid, water, and at least one pIasticizer into a substantially homogeneous film-forming composition having a viscosity of less than about 100,000 cP as measured at a temperature less than about 100 degrees C.
The method further includes extracting a portion of the water from the film-forming composition to form a dried portion having a water content less than or equal to about 2S
percent by weight, and forming the dried portion of the film-forming composition into a film.
The invention also includes a method of producing a non-gelatin film that includes combining at least one non-gelatin hydrocolloid, water, and at least one plastici~er into a substantially homogeneous film-forming composition having a viscosity of less than about 100,000 cP as measured at a temperature less than about 100 degrees C. The method further includes extracting a portion of the water from the film-forming composition to form a dried portion, and forming the dried portion of the film-forming composition into a film, wherein the film has a tensile strength at rctpt~are of at least about.5 N at room ten~p~rat~are.
Tn mother method accordia~g to the invention, the nmthod includes combining at Ieast one non-gelatin hydrocolloid9 water, and at least one plastici~er into a~ substantialig~
homogeneous film-foa~rning coanposition haring a vlsccrsit~° of lea than about 100;000 ch as measured at a temperag~are less than about 100 degrees C, and then extracting a portion of the water from the film-forming composition to fornn a dried portion. '1 he dried portion of the film-forming composition is formed into a film having a percent elongati~rn of at least about 50 percent at rupture at room temperature.
These and other aspects of the invention will be apparent to those skilled in the art from a reading of the following description of embodiments of the invention together with the drawings. The embodiments as set forth herein are not intended to limit the scope of the invention, which is intended to cover equivalent materials, methods, devices, and compositions as set forth in the appended claims.
Brief Description of the Drawings Figure 1 is a flow chart showing a process for producing an edible non-gelatin film;
Figure 2 is a schematic representation of an apparatus for performing the manufacturing process of Figure 1;
Figure 3 is a longitudinal cross-sectional view of a extruder/dryer portion of the apparatus of Figure 2;
Figure 4 is a longitudinal cross-sectional view of an extrusion die for use in the apparatus of Figure 2;
Figure 5 is a liquid-filled oral dosage form including a shell comprising a film produced according the manufacturing process of in Figure 1; and Figure 6 is an oral dosage form comprising a substantially solid core: and a covering comprising a film produced according the manufacturing process of Figure 1.
Detailed Description Formulations, methods, and devices for the manufacturing of non-animal based hydrocolloid film-forming compositions are described. The film-forming composition may be used for encapsulation of dosage forms in liquid, solid, gel, paste, compacted powder, or s~a:~f.~~~,agsioa~ f~~xxa. much ~lo~age f~arxr~s c~r~ ancl~ade mcdacia~al~
plaaax~~aceuticah n~~trati~ar~al ~r dietetic d~uag dosage forms, as well as cosmetics paints, bath products or other desirably ~;n capsulated d~asage forms.
~s used herein, the teax~l 6~SOftgel" rrmans a soft gelatin c~psule~ ia~a agreement evith the accepted nomenclat~.u-e adopted by the Soft~el l~ssociation. Formerly, the accepted nomenclature was a soft elastic gelatin (SEG) capsule. Caenerally, a softgel is a one-piece, sealed, soft gelatin (or othex film-forming material) shell that contains a solution; a suspension, or a semi-solid paste.
Other encapsulated dosage forms are known to practitioners in the art and include, but are not limited to, caplets such as SOFLETTM gelatin-enrobed hard tablets made by Banner Pharmacaps, Inc.
The phrase "dosage form" as used herein encompasses any material or composition in a form suitable for encapsulation by the film-fornning composition described herein.
Thus, a dosage form can be a pharmaceutical or nutritional composition, or a cosmetic, paint, soap, bath oil or other desirably encapsulated product. The dosage form can be a solid, liquid, gel, compacted powder, suspension or any other form suitable for encapsulation.
The term "encapsulated dosage form" refers to any dosage form encapsulated with a non-animal hydrocolloid film-forming composition as set forth herein. The encapsulated dosage form can be in any form known to practitioners in the art, such as but not limited to a so$gel or caplet.
The terms "enrobe" and "encapsulate" as used herein mean placing a dosage form inside of a film-forming composition, such that the dosage form is completely surrounded by the ~Im-forming composition. By methods known to practitioners in the art, the dosage form can be inserted into the film-forming composition in some manner, or the film-forming composition can be wrapped around the dosage form.
t~ "capsule shell" as used herein refers to the film-forming composition described herein when used to encapsulate a substance such as a drug dosage form.
"Capsule" refers to a soi~gel, caplet, or any other encapsulated dosage form known to practitioners in the art, or a portion thereof.
The phrase "solids content" as used herein refers to the ratio of the weight of the da-3~ falgm-foa-mi~ag co~~po~i~.ic~aa ~,~aa~~poa~eeraE~ tea tlae total weight of the ce~ixap~~ition~
expressed as a percentage.
The adjective k'dry" or ~'dried~' as used herein a'~ea~as relatively fxee of water or other liquids. The verb 'sdrg~" refers to the act of making day or more dry such as by e~~ixacting or removing water.
Manufacture of uniform capsule shells requires a film-forming composition that has good "machineability," i.e., it is important that the film-forming composition in a preferred embodiment be able to be brought into contact with rollers or other machine pats during processing without sticking onto these machine parts. However, some stickiness is required for proper seam formation and, in the manufacture of caplets, to improve contact between the encapsulating material and the solid tablet core.
Physical characteristics for proper machineability of the film-forming composition described herein during film formation, capsule shell formation and encapsulation of a dosage form, regardless of the method or machine used, include desirable extensibility, sealability, viscosity and tensile strength at rupture of the film-forming composition as known to practitioners in the art.
Z O The term "extensibility" as used herein defines the increase in length of the film-forming composition set forth herein on application of a tensile force (pull).
The term "percent elongation" is also used herein to refer to this property. A
preferable maximum increase in length at rupture for a 50 mm long film of about 20 mm wide is at least about 50% of the unstretched length at rupture. Preferably, a 50 mm long film elongates between about 20 mm and about 80 rnm, and most preferably between about 35 mm and about 70 mm.
'The term "sealability" refers to the ability of one or more film of the film-forming composition set forth herein to fuse together using methods known to practitioners in the art, such as but not limited t~ the application of heat and/or pressure. The seam that is created in the film upon fusing should be continuous and strong to prevent leakage of encapsulated dosage forms.
The tensile strength at rupture of a film made from one embodiment of a film-forming composition as set forth herein having a moisture content of between about 5°/~
and about 20~/o is preferably between about 5 l~T and about 100 I~, and most preferably ~5 between about l O RT and about ~01~, as measured by methods known to practitioners in the art. one sui~:~bh rb~aeaaa~ of a~aea~~~ri~ag the tensile streaagth ~t:
r2alature is by ease of ~ T~-~~T2 Tea~t~are I~nalg~~er by Stable T~icro Systems ~Surreyg I~~).
one embodiment of a f lm-forming composition c~amprises a blend of iota and l~appa carrageenan, thus ~vercogning the rec~gni~ed de~ciencie.s of happy carrageenan. A
film-forming composition having the desired physical properties of extensibility, seaiability, viscosity and tensile strength at rupture is provided. The kappa carrageenan provides gel strength while the iota carrageenan provides flexibility to the hydrocolloid film. No additional gelling salts or processing aids, such as surfactants or buff i , are necessary for producing a suitable film-forming composition of the invention.
Thus, due to the use of less expensive starting materials and fewer ingredients, the film-forming composition set forth herein provides a more cost effective film-forming material than heretofore available.
An embodiment of a film-forming composition according to the invention comprises from about 1% to about 15% by weight commercially available iota carrageenan, such as but not limited to TIC Pretested~ COLLOID ~81M, available from TIC Gums of Belcamp, Maryland. Other available forms of iota carrageenan as known to practitioners in the art are also suitable for use herein. In such an embodiment, iota carrageenan preferably is present in an amount of from 2% to about 10% by weight of the composition, and more preferably in an amount of from 2.5% to about 7.5% by weight of the composition.
An embodiment of the film-forming composition also comprises kappa carrageenan in an amount less than or equal to 50°/~ by weight of total carrageenan in the film-forming composition. Preferably, in this embodiment, kappa carrageenan is present in an amount of less than or equal to about 100°/~ by weight of iota carrageenan, more preferably in an amount less than about 100°/~ by weight of iota carrageenan, provided the total amount of carrageenan does not exceed 20°/~ by weight of the composition. Kappa carrageenan is present in an amount of from about 0.1 % to about 15% by weight of the composition, and more preferably in an amount of from about 0.5% to about 7.5% by weight of the composition. Kappa carrageenan from any commercial source is acceptable, such as TIC
Pretested~ COLLOID 71 OI-I, available from TIC Gums of Belcarnp, Maryland.
Other commercial sources of kappa carrageenan as known to practitioners in the art are also suitable for use herein.
~ rnia~t~are of l~~ppa c~rr~,gaera~~~ ~r~cl ~ glucona~ma~~~ ~ucl~ as bud:
a~ot: laxa'it~d t:o koxajac flour, as known to practitioners in the art, may be used in place of some or all of the ldappa carrageenan in a~ composition accordiaig to the inventioaa. One ea~amplr; of such a mixture is IZTjJT~ICOL~ GP751, a commercially available blend of lbappa carrageenan and konjac flour, sold by FMC Biopolymer of Philadelphia, PA. Other blends of kappa carrageenan and glucomannans as known to practitioners in the art are also suitable for use herein in place of some or all of the kappa carrageenan.
The total amount of carrageenan in one embodiment of the composition 1s Iess than or equal to about 20% by weight of the composition. Preferably, the total amount of carrageenan is less than or equal to about I O% by weight of the composition.
Other hydrocolloids as known to practitioners in the art optionally can be present in an embodiment of the composition in limited amounts. In such an embodiment, the total amount of all hydrocolloids, including the carrageenans but excluding bulking agents, preferably does not exceed 22% by weight of the composition. Preferably, such hydrocolloids may include viscosity agents that can modify the physical properties of the final gel or filin: Practitioners in the art appreciate that adding plant-based hydrocolloids and gums to a film-forming composition can increase the viscosity of the composition.
Viscosity agents suitable for use in an embodiment of the composition disclosed herein include, but are not limited to alginates, guar, pectin, locust bean gum, xanthan gam, agar;
unmodified starch, modified pregelatinized starch, gellan gum and other viscosity agents known to practitioners in the art. Hydrocolloids acting as viscosity agents optionally may be added to the film-forming composition in amounts less than or equal to about 2% by weight of the composition to increase the viscosity of the composition.
'The hydrocolloids, including those used as viscosity agents but excluding those used as bulking agents and carrageenans, can be present in an embodiment of the composition in an amount less than 100°/~ by weight of the amount of iota carrageenan, preferably in an amount less than or equal to the amount of kappa carrageenan, and most preferably in an amount less than 2°/~ by weight of the composition.
The total amount of all hydrocolloids, including the carrageenans but excluding bullring agents, preferably does not exceed 22°,/~ by weight of the composition.
In one embodiment of a film-forming composition according to the invention, the composition comprises a bulking agent, such as a modified starch. The bulking agent ig~cr~ ~s~~ the ~~olid~ caan~~~t of ~:he ~lxa~-f~~rra~iaag c~ra~pc~sitioa~~
tl~erelay co~a~:ributib~g tee a redaction in the amount of energ~T and time necessargr to dry the filrr~-forming composition once formed into a capsule or capsule shell. such a bulking agent preferably is a low viscosit~;r ~~aodi~ed starch that contributes only aa~inirnally to gel formation, bast sees to increase elm strength and sealability of the elm-forming composition, and reduces water content in the wet formulation. Further, the bulking agent provides some adhesiveness, minimizes syneresis of the kappa carrageenan, improves seam formation and increases viscosity ofthe film-forming composition. Preferably, the bulking agent is a Io~viscosity starch ether or esterified starch as known to practitioners in the art, such as but not limited to N-LOK~ (starch sodium octenyl succinate), a modified waxy maize starch with corn syrup solids added, sold by National Starch & Chemical Company of Bridgewater, New S Jersey. Preferably, the modified starch is potato, corn, or maize based.
Optionally, up to 30% of the modified starch can be replaced with conventional unmodified starch and/or modified pregelatinized starch such as, but not limited to, Ultra Sperse~ M by National Starch and Chemical Company of Bridgewater, New Jersey. The film-forming composition leas a weight ratio of bulking agent to total carrageenan of from about 1: I to about 20:1, and preferably from about 2:1 to about 15:1. The bulking agent comprises from about I O% to about 60% by weight of the total film-forming composition and preferably from about I S% to about 50% by weight of the total film-forming composition.
Those skilled in the art will recognize other bulking agents, such as but not limited to modified pregelatinized starch, guar gum, gum arabic and locust bean gum, can be used in IS the composition. However, severely hydrolyzed starches and dextrins are not recommended for use in the composition.
An embodiment of a film-forming composition according to the invention may further comprise one or more plasticizer selected from those known to practitioners in the art. A plasticizes provides extensibility and improved sealability in the film-forming composition, allowing for formation of strong seams during encapsulation of a dosage form. Also, plasticizers reduce the tensile strength of films made from the film-forming composition. A preferable plasticizes is a combination of sorbitol syrup and maltitol syrup, most preferably a combination of a non-crystallizing sorbitol syrup, such as SPECIALTY acquired from SPI Polyols of New Castle, Delaware, and L~CASIN~, a maltitol syrup acquired from Moquette of Keokuk, Iowa. Non-crystallizing sorbitol is pb~.ferablr~ o~Jeh r~~al~r ~~axbitol because re~al~r sorbitol is b~lie~ed to csu~e bl~aolrling ila capsules, a defect where white cagystals form on the surface of capslales during storage.
Acceptable substitutes for n~n-crgystallizing sorbitol include other plasticizers as known to practitioners in the are, such as but slot llmlted to glycerin, polyethylene glycol and combinations thereof The amount of plasticizes used in the film-forming composition is from about 10°/~ to about 50°/~ by weight of the total film-forming composition, and preferably from about 12% to about 36% by weight ofthe total film-forming composition.
Il An embodiment of a film-forming composition according to the inventie~
comprises water in an amount sufficient to bring the total composition to 100%
by weight.
Generally, water is present in an amount from about 10% to about 90% by weight of the composition. Preferably, water is present in an amount of from about 14% to about 79%
by weight of the composition, and more preferably from about 20% to about 60%
by weight of the composition. Preferably, the water is distilled water. If the film-forming composition is used to form medicinal, nutritional or other softgels or caplets intended for human use or consumption, purified distilled water is preferable.
As known to practitioners in the art, a film-forming composition according to the invention can also contain other ingredients, such as taste modif ers, opacifying and coloring agents, preservatives, and similar additives that do not significantly alter filin-forming capabilities. The additives can be added in any amount known to practitioners in the art to achieve the desired effect without altering the film-forming properties of the composition. Preferably, the total amount of all additives does not exceed about 5% by weight of the composition, more preferably, it does not exceed about 2% by weight of the composition.
In one erilbodirnent, the solids content of the wet film-forming composition is from about 11 °/~ to about 90% by weight of the wet composition, preferably from about 40°/~ to about 90°/~ by weight, most preferably fr~m about 50°/~ to about g0% by weight of the wet composition.
The preferred physical characteristics of the wet film-forming composition are based upon the encapsulation of dosage forms using encapsulation machinery as known to practitioners in the art. ~ne method of capsule production known in the art uses a rotary die process in which a molten mass of a gelatin film-forming composition is fed from a reservoir onto cooled drums to form two spaced sheets or ribbons in a semi-molten state.
'fl~r~~;~ sh~e~:~ ~r~ f~~1 ~rox~aa~l rollers end brob~ght together at a convergent angle into the nip of a pair of roller dies that include opposed die cavities. .~ dosage form is fed into the wedge-shaped joinder ofthe sheets. The sheets are continuously con veyed be~een the dies, with the dosage fonx~ to be encapsulated, such as a medicament being trapped between the sheets inside the die cavities. The sheets are then pressed together ('ssealed"), and severed around each die so that opposed edges of the sheets seal together to encapsulate or enrobe the dosage form, forming a capsule. The part of the sheet that is severed from the segments forming the capsules is collected and either discarded-or recycled, depending on the content of the dosage form. The capsules may be finally dried to increase the film integrity and packaged for later distribution and sale.
Other encapsulating machines and methods applicable for use with the film-forming composition described herein are known to practitioners in the art, such as but not limited to the method of enrobing hard tablets (SOFLETTM) as disclosed and claimed in U.S. Patent Nos.
5,146,730 and 5549,983.
In one embodiment of a process for forming a capsule using a film forming composition as described herein, a film-forming composition is first formed by mixing all materials together and heating with stirring until a smooth liquid, free of particulates, is formed. Preferably, hydrocolloids comprising kappa and iota carrageenan are mixed together with a bulking agent and any other dry optional ingredients. A
plasticizer is added with mixing to the dry mix. Water is then added with continued mixing and the entire mixture is heated until the ingredients are uniformly dispersed. Additives such as colorants, opacifiers, preservatives, flavorants and the like as known to practitioners in the art can be added as desired during the mixing process.
In one embodiment, all the dry ingredients (kappa carrageenan, iota carrageenan, and bulki~ag agent, as well as dry additives) are blended together to form a, dry mix. In a separate container, water and plasticizer, as well as any liquid additives, are mixed together as a liquid mix and heated to at least about 75°C, preferably about 90°C. While stirring the hot liquid mix, the dry mix is slowly added to the hot liquid mix to minimize formation of large lumps. The dispersion formed is heated with mixing to a temperature of from about 85°C to about 95°C. The temperature is maintained with mixing until the film-forming composition melts to form a smooth liquid free of particulates.
A film-forming composition ia~ liquid form can be subjected to one or more tr~at~xea~t~ ~s r;~aoen~a~ tea pxa~~~it.ion~r~ ia~ flee art. 'I'lae t~-~~~aea~t~ can iraclu~le ca~ti~y the liquefied composition into a ribbon or sheet, drying the ribbon, end conditioning it to a predetermined mois~are content, t~,~pically frown about a°~~ to abca ~ut~ 30°~'~ moisture by weight of the ribbon, preferably from ~bo~at 10°~~ to about '~~°~'~
anoisture bag v~eight of the ribbon, as known to practitioners in the art. The dry ribbon or sheet can be stored, or used directly afrer drying. Preferably, the dry ribbon or sheet is used to encapsulate a dosage form, such as by use of a rotary die encapsulation machine, although other methods of encapsulation as known to practitioners in the art may also be used.
Many non-gelatin film-forming compositions require a high percentage of water included in the composition to allow the hydrocolloids to fully hydrate and/or to allow the composition to be flowable enough for easy use in manufacturing. Most films do not have sufficient strength at such a high water content to be directly usable in a rotary die encapsulation process. Films cast compositions having a high water content take too long to dry to practically be used in a continuous rotary die encapsulation process.
Accordingly, it is desirable to lower the water content of such film-forming compositions prior to film formation. Tn one process according to the invention, a film-forming composition having a high water content and low viscosity is metered into an extruder/dryer to reduce the water content to a level that yields a dried composition that can be readily formed into a usable film. The dried film-forming composition can be continuously extruded into a ribbon, film or other useful profile shape.
I S Alternatively, some film-forming compositions can be cast into a wet film on the drum of a rotary die encapsulation machine and the wet film used to encapsulate a dosage form. Encapsulated dosage forms include, but are not limited to drug dosage forms, nutritional supplements, cosmetics, bath oils and gels, paint balls and the like.
The film-forming composition can also be formed by adding a dry mix and a liquid mix as defined elsewhere herein to an extruder, wherein the dry and liquid mixes are mixed together and heated, then extruded through dies into sheets, films or tubes. A
premixed film-forming composition may also be added to an extruder for extrusion to form sheets, films or tubes. The water content of the film forming composition may be adjusted to the desired Level in the extruder. The extruded composition is fed to an encapsulation machine ~5 for the manufacture of encapsulated dosage forms. Encapsulated dosage forms include, but ~r~ a~ot li~~Ited to drug dosage ~°~ard~~~9 nt~trit~ional s~applegai~;a~t~? cosmetics, bath oils and gals, paint balls and the like.
~2 s used herein, the term 66sheet" or "ribbon' is meant to include any form of the film-forming composition suitable for encapsulation of a dosage form as Isno~cn to practitioners in the arl, including but not limited to sheets, films, tubes, hemispheres, cones and the like. tWet cast or extruded ribbons are preferably from 0.4 mm to about 1.0 mm thick, though other thicknesses can be formed and used as known to practitioners in the art.
Dry ribbons are typically from about 0.5 mm to about 0.7 mm thick, though thi~er or thinner dry ribbons can be formed as known to practitioners in the art. The thickness of a dry or wet ribbon is determinable by a practitioner in the art based on the desired end use.
Preferably, the moisture content of the dry ribbon is from about 5% to about 25% by S weight of the ribbon, more preferably from about 10% to about 20% by weight of the ribbon.
Once the film-forming composition is formed into the desired shape, it can be used to encapsulate dosage forms including liquids, solids, gels and suspensions, according to methods known to practitioners in the art. Typically, fox encapsulation, a film is heated to and maintained at a temperature of from about 60°C to about 100°C, preferably from about 7S°C to about 9S°C, during the encapsulation process. For example, when a rotary die encapsulation machine is used, the film is heated by a wedge that is located above the dies.
The film is maintained at a temperature of from about 60°C to about 99°C, typically from about 75°C to about 95°C, during encapsulation of the dosage forni. ~ther examples of equipment, heating methods and temperatures therefore are known to practitioners in the art.
During encapsulation, the ribbon is frequently lubricated to prevent adherence to the machinery and prevent entrapramnt of air bubbles within the capsule.
Suitable lubricants are known to practitioners in the art, and include, but are not limited to, triglycerides, mineral oil and acetylated monoglycerides.
~nee formed, the capsule shell of dry f lm-forming composition preferably has a solids content of from about 70°/~ to about 9S% by weight of the dry composition. Iota carrageenan is present in an amount of from about 2°/~ to about 20°/~ by weight of the dry composition, and preferably from about 2.S°/~ to about 10°/~ by weight of the dry composition. Kappa carrageenan is present in an amount of from about 0.4°/~ to about 20°/~
bar ~,~eiglal: of fihe dr~r c~a~a~apo~ itior~, tad preferably fror~a about O.S% to about 10°/~ by weight of the d~° composition. 'The bulking agent is present in an arr~o~ant of frown about 10% to about ~0°/~ by weight of the dry composition, and preferably from about 40°6° to about 70%
by weight of the drgs composition. The plastici~er is present in an amount of fxoia~ about 30~/~ to about 60°/~ by weight of the dry composition, and preferably from about 3S% to about 50% by weight of the dry composition. The water content is from about S%
to about 30% by weight of the dry composition, and preferably from ab~ut 7.5% to abou~C-20% by weight of the dry composition.
Examples of various embodiments of film-forming compositions of the invention are set forth below. Composition components are set forth by weight percentage of the total weight of the composition; "i" refers to iota carrageenan and "x" refers to kappa carrageenan.
Kappa carrageenan is nonstandardized carrageenan and iota carrageenan is standardized carrageenan (standardized with rnaltodextrin) supplied by TIC
Gums of Belcamp, Maryland. Kappa carrageenan is supplied as TIC PRETESTED~ COLLOID
710H. Standardized iota carrageenan is supplied as TIC PRETESTED~ COLLOID
~~1M.
The modified starch is N-LOK~, starch sodium octenyl succinate with corn syrup solids added, and the modified pregelatinized starch is Ultra Sperse~ M, both supplied by National Starch and Chemical Company of Bridgewater, New Jersey. SORBITOL
SPECIALTM is non-crystallizing sorbitol supplied by SPI Polyols of New Castle, Delaware.
The maltitol used is LYCASIN~, supplied by Roquette of Keokuk, Iowa. Glycerin is USP
GLI~CERIN acquired from commercial sources such as Henkel of Cincinnati, Ohio.
Titanium dioxide is supplied by Warner-Jenkinson Co., Inc., of South Plainfield, New Jersey. Water is purified, distilled water prepared in house.
E~AMPLI E 1 Kappa Carrageenan 2.0%
Iota Carrageenan 2.0%
Modified Starch 20.0/~
Ratio of starchaotal 5:1 carrageenan Sorbito1 SpecialT~~ 36 .0%
Distilled Water _ T40.0/~ -- - _l ~a~l~~~ E 2 _ kappa Carrageenan 2.0%
Iota Carrageenan 2.0/~
l~llodiiaed Starch I5.0!~
Ratio of starch:total 7.5:2 carrageenan Sorbitol S ecialT~" 35.0/~
Titanium Dioxide 0.5%
Distilled Water 45.5%
Kappa Carrageenan 1.0%
Iota Carrageenan 3.0%
Modified Starch 20%
Ratio of starchaotal 5:1 carrageenan Sorbitol S ecialTM 30.0%
Titanium Diode 1.0%
Distilled Water 45.0%
E~~AMP E 4 L
_ 2.0%
Kappa Carrageenan _ 3.0%
Iota Carrageenan Modified Starch 20%
Ratio of starchaotal 4:1 carrageenan Sorbitol SpecialTM 35.0%
Titanium Dioxide O.S%
Distilled Water 39.5%
Kappa Carrageenan l.S%
Iota Carrageenan 2.5%
Modified Starch 20.0%
Ratio of starchaotal 5:1 carrageenan Calycerin (CTSP) 25.0/' Titanium Dioz~ide O.S%
Distilled Water 50.5/~
Kappa Carrageenan 1.S%
Iota Carrageenan 2.5%
Modified Starch 20.0!~
Ratio of starchaotal S:1 carra eenan Ii laltitol 25.0/~
Titanium I~io~~de 0.5/~
Distalled Water SO.SlQ
Kappa Carrageenan 1.5%
Iota Carrageenan 2.5%
Modified Starch 20.0%
Ratio of starchaotal 5:1 carry eenan Glycerin (LTSP) I2.5%
Sorbitol SpecialTM 12.5%
Titanium Dioxide 0.5%
Distilled Water 50.5%
XAMPL
_ I .5%
Kap a Carry eenan _ 2.5%
Iota Carrageenan ~
Modified Starch 25.0%
Ratio of starchaotal 6.25:1 carrageenan Maltitol 5.0%
Sorbitol SpecialTM 15.0%
Titanium Dioxide 0.5%
Distilled Water 50.5%
_ EXAMFL E 9 Ka pa Carry eenan 2.5%
Iota Carrageenan 2.5%
Modified Starch 23.0%
Ratio of starchaotal 4~.6: I
carrageenan Maltitol 16%
Sorbitol S ecialTM ~%
Titanium Dioxide Distilled Water 4~10 Kappa Carry eenan 1.5/~
Iota Carrageenan ~.5%
T~~dilied Starcla 25.0/~
Ratio of starch:to~al 5:1 carry, een~n Maltitol 7.0!0 Sorbitol Special'~~ 13.0%
Tit~ni~am Dio~~ide 0010%
Distilled Water 4~.~0/~
1~
E~~AMPLE 11 Kappa Carrageenan l.S%
Iota Carrageenan 3.S%
Modified Starch 25.0%
Ratio of starchaotal 5:1 carrageenan Maltitol 8.0%
Sorbitol SpecialTM 15.0%
Titanium Dioxide 0.10%
Distilled Water 46.90%
Kap a Carrageenan 2.S% _ Iota Carra eenan 2.S%
Modified Starch 40.0%
Pregelatini~ed Starch 5.0%
Ratio of starchaotal 9:1 carrageenan Maltitol 3.75%
Sorbitol SpecialTM 18.75%
Titanium Dioxide Distilled Water 27.50!
The film-forming compositions of examples 1-12 were cast into films and dried to between about S°/~ and about 15°!~ moisture. 'The films were cut into strips 20 mm wide by SO mm long. The films for Examples 2-12 were tested for tensile strength at rupture and extensibility using a TA-XT2 Texture P~nnaly~er manufactured by Stable Micro Systems, (Surrey, UK). The following table charts the tensile strength and extensibility of the resulting films, where the values are mean values with standard deviations taken from four
Unfortunately, holding the mass at this high temperature for an extended period of time as is typically required for production encapsulation causes an undesirable breakdown of the hydrocolloids in the film-forming mixture.
Accordingly, there is a need for a process that permits the use of a variety of types arid concentrations of hydrocolloids and permits the viscosity of a film-forming composition to be sufficiently low such that the composition can flow under gravity. It is also desirable to have a process for producing films comprising many types of hydrocolloids that permits a film-forming composition comprising such hydrocolloids to be processed at temperatures that do not cause substantial degradation of the film-forming materials.
Summaay ~f the fuventi0n The present invention includes a method of producing a non-gelatin film. The method includes combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition comprising at least about 40 percent water by weight. The method farther includes extracting a portion of the ~~~~ter from the fll~rxa-fc~a~~ia~g; cotral-~~si~:iob~ to foa~~~ ~ dried portion having a water conEent ~f less than or equal to about 2~ percent by vreight. °The method als~
includes forming the dried portion of tlm film-~°~arming coanposition into a lalm.
°fhe invention also includes a method of producing a non-gelatin falm that includes combining apt least one non-gelatin hydrocolloid , water, and at least one plasticizer into ~
substantially homogeneous film-forming composition having a water content of at least about 40 percent by weight. This method further includes extracting a portion of the water q.
from the film-forming composition to form a dried portion, and forming the dried portion of the film-forming composition into a film. The film produced by such a method has a tensile strength at rupture of at least about 5 N at room temperature.
The invention further includes a method of producing a non-gelatin film including combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition comprising at least about 40 percent water by weight. A portion of the water is extracted from the film-forming composition to form a dried portion, and the dried portion of the film-forming composition is formed into a film having a percent elongation of at Ieast about 50 percent at rupture at room temperature.
In addition, the invention includes a method of producing a non-gelatin film including combining at least one non-gelatin hydrocolloid, water, and at least one pIasticizer into a substantially homogeneous film-forming composition having a viscosity of less than about 100,000 cP as measured at a temperature less than about 100 degrees C.
The method further includes extracting a portion of the water from the film-forming composition to form a dried portion having a water content less than or equal to about 2S
percent by weight, and forming the dried portion of the film-forming composition into a film.
The invention also includes a method of producing a non-gelatin film that includes combining at least one non-gelatin hydrocolloid, water, and at least one plastici~er into a substantially homogeneous film-forming composition having a viscosity of less than about 100,000 cP as measured at a temperature less than about 100 degrees C. The method further includes extracting a portion of the water from the film-forming composition to form a dried portion, and forming the dried portion of the film-forming composition into a film, wherein the film has a tensile strength at rctpt~are of at least about.5 N at room ten~p~rat~are.
Tn mother method accordia~g to the invention, the nmthod includes combining at Ieast one non-gelatin hydrocolloid9 water, and at least one plastici~er into a~ substantialig~
homogeneous film-foa~rning coanposition haring a vlsccrsit~° of lea than about 100;000 ch as measured at a temperag~are less than about 100 degrees C, and then extracting a portion of the water from the film-forming composition to fornn a dried portion. '1 he dried portion of the film-forming composition is formed into a film having a percent elongati~rn of at least about 50 percent at rupture at room temperature.
These and other aspects of the invention will be apparent to those skilled in the art from a reading of the following description of embodiments of the invention together with the drawings. The embodiments as set forth herein are not intended to limit the scope of the invention, which is intended to cover equivalent materials, methods, devices, and compositions as set forth in the appended claims.
Brief Description of the Drawings Figure 1 is a flow chart showing a process for producing an edible non-gelatin film;
Figure 2 is a schematic representation of an apparatus for performing the manufacturing process of Figure 1;
Figure 3 is a longitudinal cross-sectional view of a extruder/dryer portion of the apparatus of Figure 2;
Figure 4 is a longitudinal cross-sectional view of an extrusion die for use in the apparatus of Figure 2;
Figure 5 is a liquid-filled oral dosage form including a shell comprising a film produced according the manufacturing process of in Figure 1; and Figure 6 is an oral dosage form comprising a substantially solid core: and a covering comprising a film produced according the manufacturing process of Figure 1.
Detailed Description Formulations, methods, and devices for the manufacturing of non-animal based hydrocolloid film-forming compositions are described. The film-forming composition may be used for encapsulation of dosage forms in liquid, solid, gel, paste, compacted powder, or s~a:~f.~~~,agsioa~ f~~xxa. much ~lo~age f~arxr~s c~r~ ancl~ade mcdacia~al~
plaaax~~aceuticah n~~trati~ar~al ~r dietetic d~uag dosage forms, as well as cosmetics paints, bath products or other desirably ~;n capsulated d~asage forms.
~s used herein, the teax~l 6~SOftgel" rrmans a soft gelatin c~psule~ ia~a agreement evith the accepted nomenclat~.u-e adopted by the Soft~el l~ssociation. Formerly, the accepted nomenclature was a soft elastic gelatin (SEG) capsule. Caenerally, a softgel is a one-piece, sealed, soft gelatin (or othex film-forming material) shell that contains a solution; a suspension, or a semi-solid paste.
Other encapsulated dosage forms are known to practitioners in the art and include, but are not limited to, caplets such as SOFLETTM gelatin-enrobed hard tablets made by Banner Pharmacaps, Inc.
The phrase "dosage form" as used herein encompasses any material or composition in a form suitable for encapsulation by the film-fornning composition described herein.
Thus, a dosage form can be a pharmaceutical or nutritional composition, or a cosmetic, paint, soap, bath oil or other desirably encapsulated product. The dosage form can be a solid, liquid, gel, compacted powder, suspension or any other form suitable for encapsulation.
The term "encapsulated dosage form" refers to any dosage form encapsulated with a non-animal hydrocolloid film-forming composition as set forth herein. The encapsulated dosage form can be in any form known to practitioners in the art, such as but not limited to a so$gel or caplet.
The terms "enrobe" and "encapsulate" as used herein mean placing a dosage form inside of a film-forming composition, such that the dosage form is completely surrounded by the ~Im-forming composition. By methods known to practitioners in the art, the dosage form can be inserted into the film-forming composition in some manner, or the film-forming composition can be wrapped around the dosage form.
t~ "capsule shell" as used herein refers to the film-forming composition described herein when used to encapsulate a substance such as a drug dosage form.
"Capsule" refers to a soi~gel, caplet, or any other encapsulated dosage form known to practitioners in the art, or a portion thereof.
The phrase "solids content" as used herein refers to the ratio of the weight of the da-3~ falgm-foa-mi~ag co~~po~i~.ic~aa ~,~aa~~poa~eeraE~ tea tlae total weight of the ce~ixap~~ition~
expressed as a percentage.
The adjective k'dry" or ~'dried~' as used herein a'~ea~as relatively fxee of water or other liquids. The verb 'sdrg~" refers to the act of making day or more dry such as by e~~ixacting or removing water.
Manufacture of uniform capsule shells requires a film-forming composition that has good "machineability," i.e., it is important that the film-forming composition in a preferred embodiment be able to be brought into contact with rollers or other machine pats during processing without sticking onto these machine parts. However, some stickiness is required for proper seam formation and, in the manufacture of caplets, to improve contact between the encapsulating material and the solid tablet core.
Physical characteristics for proper machineability of the film-forming composition described herein during film formation, capsule shell formation and encapsulation of a dosage form, regardless of the method or machine used, include desirable extensibility, sealability, viscosity and tensile strength at rupture of the film-forming composition as known to practitioners in the art.
Z O The term "extensibility" as used herein defines the increase in length of the film-forming composition set forth herein on application of a tensile force (pull).
The term "percent elongation" is also used herein to refer to this property. A
preferable maximum increase in length at rupture for a 50 mm long film of about 20 mm wide is at least about 50% of the unstretched length at rupture. Preferably, a 50 mm long film elongates between about 20 mm and about 80 rnm, and most preferably between about 35 mm and about 70 mm.
'The term "sealability" refers to the ability of one or more film of the film-forming composition set forth herein to fuse together using methods known to practitioners in the art, such as but not limited t~ the application of heat and/or pressure. The seam that is created in the film upon fusing should be continuous and strong to prevent leakage of encapsulated dosage forms.
The tensile strength at rupture of a film made from one embodiment of a film-forming composition as set forth herein having a moisture content of between about 5°/~
and about 20~/o is preferably between about 5 l~T and about 100 I~, and most preferably ~5 between about l O RT and about ~01~, as measured by methods known to practitioners in the art. one sui~:~bh rb~aeaaa~ of a~aea~~~ri~ag the tensile streaagth ~t:
r2alature is by ease of ~ T~-~~T2 Tea~t~are I~nalg~~er by Stable T~icro Systems ~Surreyg I~~).
one embodiment of a f lm-forming composition c~amprises a blend of iota and l~appa carrageenan, thus ~vercogning the rec~gni~ed de~ciencie.s of happy carrageenan. A
film-forming composition having the desired physical properties of extensibility, seaiability, viscosity and tensile strength at rupture is provided. The kappa carrageenan provides gel strength while the iota carrageenan provides flexibility to the hydrocolloid film. No additional gelling salts or processing aids, such as surfactants or buff i , are necessary for producing a suitable film-forming composition of the invention.
Thus, due to the use of less expensive starting materials and fewer ingredients, the film-forming composition set forth herein provides a more cost effective film-forming material than heretofore available.
An embodiment of a film-forming composition according to the invention comprises from about 1% to about 15% by weight commercially available iota carrageenan, such as but not limited to TIC Pretested~ COLLOID ~81M, available from TIC Gums of Belcamp, Maryland. Other available forms of iota carrageenan as known to practitioners in the art are also suitable for use herein. In such an embodiment, iota carrageenan preferably is present in an amount of from 2% to about 10% by weight of the composition, and more preferably in an amount of from 2.5% to about 7.5% by weight of the composition.
An embodiment of the film-forming composition also comprises kappa carrageenan in an amount less than or equal to 50°/~ by weight of total carrageenan in the film-forming composition. Preferably, in this embodiment, kappa carrageenan is present in an amount of less than or equal to about 100°/~ by weight of iota carrageenan, more preferably in an amount less than about 100°/~ by weight of iota carrageenan, provided the total amount of carrageenan does not exceed 20°/~ by weight of the composition. Kappa carrageenan is present in an amount of from about 0.1 % to about 15% by weight of the composition, and more preferably in an amount of from about 0.5% to about 7.5% by weight of the composition. Kappa carrageenan from any commercial source is acceptable, such as TIC
Pretested~ COLLOID 71 OI-I, available from TIC Gums of Belcarnp, Maryland.
Other commercial sources of kappa carrageenan as known to practitioners in the art are also suitable for use herein.
~ rnia~t~are of l~~ppa c~rr~,gaera~~~ ~r~cl ~ glucona~ma~~~ ~ucl~ as bud:
a~ot: laxa'it~d t:o koxajac flour, as known to practitioners in the art, may be used in place of some or all of the ldappa carrageenan in a~ composition accordiaig to the inventioaa. One ea~amplr; of such a mixture is IZTjJT~ICOL~ GP751, a commercially available blend of lbappa carrageenan and konjac flour, sold by FMC Biopolymer of Philadelphia, PA. Other blends of kappa carrageenan and glucomannans as known to practitioners in the art are also suitable for use herein in place of some or all of the kappa carrageenan.
The total amount of carrageenan in one embodiment of the composition 1s Iess than or equal to about 20% by weight of the composition. Preferably, the total amount of carrageenan is less than or equal to about I O% by weight of the composition.
Other hydrocolloids as known to practitioners in the art optionally can be present in an embodiment of the composition in limited amounts. In such an embodiment, the total amount of all hydrocolloids, including the carrageenans but excluding bulking agents, preferably does not exceed 22% by weight of the composition. Preferably, such hydrocolloids may include viscosity agents that can modify the physical properties of the final gel or filin: Practitioners in the art appreciate that adding plant-based hydrocolloids and gums to a film-forming composition can increase the viscosity of the composition.
Viscosity agents suitable for use in an embodiment of the composition disclosed herein include, but are not limited to alginates, guar, pectin, locust bean gum, xanthan gam, agar;
unmodified starch, modified pregelatinized starch, gellan gum and other viscosity agents known to practitioners in the art. Hydrocolloids acting as viscosity agents optionally may be added to the film-forming composition in amounts less than or equal to about 2% by weight of the composition to increase the viscosity of the composition.
'The hydrocolloids, including those used as viscosity agents but excluding those used as bulking agents and carrageenans, can be present in an embodiment of the composition in an amount less than 100°/~ by weight of the amount of iota carrageenan, preferably in an amount less than or equal to the amount of kappa carrageenan, and most preferably in an amount less than 2°/~ by weight of the composition.
The total amount of all hydrocolloids, including the carrageenans but excluding bullring agents, preferably does not exceed 22°,/~ by weight of the composition.
In one embodiment of a film-forming composition according to the invention, the composition comprises a bulking agent, such as a modified starch. The bulking agent ig~cr~ ~s~~ the ~~olid~ caan~~~t of ~:he ~lxa~-f~~rra~iaag c~ra~pc~sitioa~~
tl~erelay co~a~:ributib~g tee a redaction in the amount of energ~T and time necessargr to dry the filrr~-forming composition once formed into a capsule or capsule shell. such a bulking agent preferably is a low viscosit~;r ~~aodi~ed starch that contributes only aa~inirnally to gel formation, bast sees to increase elm strength and sealability of the elm-forming composition, and reduces water content in the wet formulation. Further, the bulking agent provides some adhesiveness, minimizes syneresis of the kappa carrageenan, improves seam formation and increases viscosity ofthe film-forming composition. Preferably, the bulking agent is a Io~viscosity starch ether or esterified starch as known to practitioners in the art, such as but not limited to N-LOK~ (starch sodium octenyl succinate), a modified waxy maize starch with corn syrup solids added, sold by National Starch & Chemical Company of Bridgewater, New S Jersey. Preferably, the modified starch is potato, corn, or maize based.
Optionally, up to 30% of the modified starch can be replaced with conventional unmodified starch and/or modified pregelatinized starch such as, but not limited to, Ultra Sperse~ M by National Starch and Chemical Company of Bridgewater, New Jersey. The film-forming composition leas a weight ratio of bulking agent to total carrageenan of from about 1: I to about 20:1, and preferably from about 2:1 to about 15:1. The bulking agent comprises from about I O% to about 60% by weight of the total film-forming composition and preferably from about I S% to about 50% by weight of the total film-forming composition.
Those skilled in the art will recognize other bulking agents, such as but not limited to modified pregelatinized starch, guar gum, gum arabic and locust bean gum, can be used in IS the composition. However, severely hydrolyzed starches and dextrins are not recommended for use in the composition.
An embodiment of a film-forming composition according to the invention may further comprise one or more plasticizer selected from those known to practitioners in the art. A plasticizes provides extensibility and improved sealability in the film-forming composition, allowing for formation of strong seams during encapsulation of a dosage form. Also, plasticizers reduce the tensile strength of films made from the film-forming composition. A preferable plasticizes is a combination of sorbitol syrup and maltitol syrup, most preferably a combination of a non-crystallizing sorbitol syrup, such as SPECIALTY acquired from SPI Polyols of New Castle, Delaware, and L~CASIN~, a maltitol syrup acquired from Moquette of Keokuk, Iowa. Non-crystallizing sorbitol is pb~.ferablr~ o~Jeh r~~al~r ~~axbitol because re~al~r sorbitol is b~lie~ed to csu~e bl~aolrling ila capsules, a defect where white cagystals form on the surface of capslales during storage.
Acceptable substitutes for n~n-crgystallizing sorbitol include other plasticizers as known to practitioners in the are, such as but slot llmlted to glycerin, polyethylene glycol and combinations thereof The amount of plasticizes used in the film-forming composition is from about 10°/~ to about 50°/~ by weight of the total film-forming composition, and preferably from about 12% to about 36% by weight ofthe total film-forming composition.
Il An embodiment of a film-forming composition according to the inventie~
comprises water in an amount sufficient to bring the total composition to 100%
by weight.
Generally, water is present in an amount from about 10% to about 90% by weight of the composition. Preferably, water is present in an amount of from about 14% to about 79%
by weight of the composition, and more preferably from about 20% to about 60%
by weight of the composition. Preferably, the water is distilled water. If the film-forming composition is used to form medicinal, nutritional or other softgels or caplets intended for human use or consumption, purified distilled water is preferable.
As known to practitioners in the art, a film-forming composition according to the invention can also contain other ingredients, such as taste modif ers, opacifying and coloring agents, preservatives, and similar additives that do not significantly alter filin-forming capabilities. The additives can be added in any amount known to practitioners in the art to achieve the desired effect without altering the film-forming properties of the composition. Preferably, the total amount of all additives does not exceed about 5% by weight of the composition, more preferably, it does not exceed about 2% by weight of the composition.
In one erilbodirnent, the solids content of the wet film-forming composition is from about 11 °/~ to about 90% by weight of the wet composition, preferably from about 40°/~ to about 90°/~ by weight, most preferably fr~m about 50°/~ to about g0% by weight of the wet composition.
The preferred physical characteristics of the wet film-forming composition are based upon the encapsulation of dosage forms using encapsulation machinery as known to practitioners in the art. ~ne method of capsule production known in the art uses a rotary die process in which a molten mass of a gelatin film-forming composition is fed from a reservoir onto cooled drums to form two spaced sheets or ribbons in a semi-molten state.
'fl~r~~;~ sh~e~:~ ~r~ f~~1 ~rox~aa~l rollers end brob~ght together at a convergent angle into the nip of a pair of roller dies that include opposed die cavities. .~ dosage form is fed into the wedge-shaped joinder ofthe sheets. The sheets are continuously con veyed be~een the dies, with the dosage fonx~ to be encapsulated, such as a medicament being trapped between the sheets inside the die cavities. The sheets are then pressed together ('ssealed"), and severed around each die so that opposed edges of the sheets seal together to encapsulate or enrobe the dosage form, forming a capsule. The part of the sheet that is severed from the segments forming the capsules is collected and either discarded-or recycled, depending on the content of the dosage form. The capsules may be finally dried to increase the film integrity and packaged for later distribution and sale.
Other encapsulating machines and methods applicable for use with the film-forming composition described herein are known to practitioners in the art, such as but not limited to the method of enrobing hard tablets (SOFLETTM) as disclosed and claimed in U.S. Patent Nos.
5,146,730 and 5549,983.
In one embodiment of a process for forming a capsule using a film forming composition as described herein, a film-forming composition is first formed by mixing all materials together and heating with stirring until a smooth liquid, free of particulates, is formed. Preferably, hydrocolloids comprising kappa and iota carrageenan are mixed together with a bulking agent and any other dry optional ingredients. A
plasticizer is added with mixing to the dry mix. Water is then added with continued mixing and the entire mixture is heated until the ingredients are uniformly dispersed. Additives such as colorants, opacifiers, preservatives, flavorants and the like as known to practitioners in the art can be added as desired during the mixing process.
In one embodiment, all the dry ingredients (kappa carrageenan, iota carrageenan, and bulki~ag agent, as well as dry additives) are blended together to form a, dry mix. In a separate container, water and plasticizer, as well as any liquid additives, are mixed together as a liquid mix and heated to at least about 75°C, preferably about 90°C. While stirring the hot liquid mix, the dry mix is slowly added to the hot liquid mix to minimize formation of large lumps. The dispersion formed is heated with mixing to a temperature of from about 85°C to about 95°C. The temperature is maintained with mixing until the film-forming composition melts to form a smooth liquid free of particulates.
A film-forming composition ia~ liquid form can be subjected to one or more tr~at~xea~t~ ~s r;~aoen~a~ tea pxa~~~it.ion~r~ ia~ flee art. 'I'lae t~-~~~aea~t~ can iraclu~le ca~ti~y the liquefied composition into a ribbon or sheet, drying the ribbon, end conditioning it to a predetermined mois~are content, t~,~pically frown about a°~~ to abca ~ut~ 30°~'~ moisture by weight of the ribbon, preferably from ~bo~at 10°~~ to about '~~°~'~
anoisture bag v~eight of the ribbon, as known to practitioners in the art. The dry ribbon or sheet can be stored, or used directly afrer drying. Preferably, the dry ribbon or sheet is used to encapsulate a dosage form, such as by use of a rotary die encapsulation machine, although other methods of encapsulation as known to practitioners in the art may also be used.
Many non-gelatin film-forming compositions require a high percentage of water included in the composition to allow the hydrocolloids to fully hydrate and/or to allow the composition to be flowable enough for easy use in manufacturing. Most films do not have sufficient strength at such a high water content to be directly usable in a rotary die encapsulation process. Films cast compositions having a high water content take too long to dry to practically be used in a continuous rotary die encapsulation process.
Accordingly, it is desirable to lower the water content of such film-forming compositions prior to film formation. Tn one process according to the invention, a film-forming composition having a high water content and low viscosity is metered into an extruder/dryer to reduce the water content to a level that yields a dried composition that can be readily formed into a usable film. The dried film-forming composition can be continuously extruded into a ribbon, film or other useful profile shape.
I S Alternatively, some film-forming compositions can be cast into a wet film on the drum of a rotary die encapsulation machine and the wet film used to encapsulate a dosage form. Encapsulated dosage forms include, but are not limited to drug dosage forms, nutritional supplements, cosmetics, bath oils and gels, paint balls and the like.
The film-forming composition can also be formed by adding a dry mix and a liquid mix as defined elsewhere herein to an extruder, wherein the dry and liquid mixes are mixed together and heated, then extruded through dies into sheets, films or tubes. A
premixed film-forming composition may also be added to an extruder for extrusion to form sheets, films or tubes. The water content of the film forming composition may be adjusted to the desired Level in the extruder. The extruded composition is fed to an encapsulation machine ~5 for the manufacture of encapsulated dosage forms. Encapsulated dosage forms include, but ~r~ a~ot li~~Ited to drug dosage ~°~ard~~~9 nt~trit~ional s~applegai~;a~t~? cosmetics, bath oils and gals, paint balls and the like.
~2 s used herein, the term 66sheet" or "ribbon' is meant to include any form of the film-forming composition suitable for encapsulation of a dosage form as Isno~cn to practitioners in the arl, including but not limited to sheets, films, tubes, hemispheres, cones and the like. tWet cast or extruded ribbons are preferably from 0.4 mm to about 1.0 mm thick, though other thicknesses can be formed and used as known to practitioners in the art.
Dry ribbons are typically from about 0.5 mm to about 0.7 mm thick, though thi~er or thinner dry ribbons can be formed as known to practitioners in the art. The thickness of a dry or wet ribbon is determinable by a practitioner in the art based on the desired end use.
Preferably, the moisture content of the dry ribbon is from about 5% to about 25% by S weight of the ribbon, more preferably from about 10% to about 20% by weight of the ribbon.
Once the film-forming composition is formed into the desired shape, it can be used to encapsulate dosage forms including liquids, solids, gels and suspensions, according to methods known to practitioners in the art. Typically, fox encapsulation, a film is heated to and maintained at a temperature of from about 60°C to about 100°C, preferably from about 7S°C to about 9S°C, during the encapsulation process. For example, when a rotary die encapsulation machine is used, the film is heated by a wedge that is located above the dies.
The film is maintained at a temperature of from about 60°C to about 99°C, typically from about 75°C to about 95°C, during encapsulation of the dosage forni. ~ther examples of equipment, heating methods and temperatures therefore are known to practitioners in the art.
During encapsulation, the ribbon is frequently lubricated to prevent adherence to the machinery and prevent entrapramnt of air bubbles within the capsule.
Suitable lubricants are known to practitioners in the art, and include, but are not limited to, triglycerides, mineral oil and acetylated monoglycerides.
~nee formed, the capsule shell of dry f lm-forming composition preferably has a solids content of from about 70°/~ to about 9S% by weight of the dry composition. Iota carrageenan is present in an amount of from about 2°/~ to about 20°/~ by weight of the dry composition, and preferably from about 2.S°/~ to about 10°/~ by weight of the dry composition. Kappa carrageenan is present in an amount of from about 0.4°/~ to about 20°/~
bar ~,~eiglal: of fihe dr~r c~a~a~apo~ itior~, tad preferably fror~a about O.S% to about 10°/~ by weight of the d~° composition. 'The bulking agent is present in an arr~o~ant of frown about 10% to about ~0°/~ by weight of the dry composition, and preferably from about 40°6° to about 70%
by weight of the drgs composition. The plastici~er is present in an amount of fxoia~ about 30~/~ to about 60°/~ by weight of the dry composition, and preferably from about 3S% to about 50% by weight of the dry composition. The water content is from about S%
to about 30% by weight of the dry composition, and preferably from ab~ut 7.5% to abou~C-20% by weight of the dry composition.
Examples of various embodiments of film-forming compositions of the invention are set forth below. Composition components are set forth by weight percentage of the total weight of the composition; "i" refers to iota carrageenan and "x" refers to kappa carrageenan.
Kappa carrageenan is nonstandardized carrageenan and iota carrageenan is standardized carrageenan (standardized with rnaltodextrin) supplied by TIC
Gums of Belcamp, Maryland. Kappa carrageenan is supplied as TIC PRETESTED~ COLLOID
710H. Standardized iota carrageenan is supplied as TIC PRETESTED~ COLLOID
~~1M.
The modified starch is N-LOK~, starch sodium octenyl succinate with corn syrup solids added, and the modified pregelatinized starch is Ultra Sperse~ M, both supplied by National Starch and Chemical Company of Bridgewater, New Jersey. SORBITOL
SPECIALTM is non-crystallizing sorbitol supplied by SPI Polyols of New Castle, Delaware.
The maltitol used is LYCASIN~, supplied by Roquette of Keokuk, Iowa. Glycerin is USP
GLI~CERIN acquired from commercial sources such as Henkel of Cincinnati, Ohio.
Titanium dioxide is supplied by Warner-Jenkinson Co., Inc., of South Plainfield, New Jersey. Water is purified, distilled water prepared in house.
E~AMPLI E 1 Kappa Carrageenan 2.0%
Iota Carrageenan 2.0%
Modified Starch 20.0/~
Ratio of starchaotal 5:1 carrageenan Sorbito1 SpecialT~~ 36 .0%
Distilled Water _ T40.0/~ -- - _l ~a~l~~~ E 2 _ kappa Carrageenan 2.0%
Iota Carrageenan 2.0/~
l~llodiiaed Starch I5.0!~
Ratio of starch:total 7.5:2 carrageenan Sorbitol S ecialT~" 35.0/~
Titanium Dioxide 0.5%
Distilled Water 45.5%
Kappa Carrageenan 1.0%
Iota Carrageenan 3.0%
Modified Starch 20%
Ratio of starchaotal 5:1 carrageenan Sorbitol S ecialTM 30.0%
Titanium Diode 1.0%
Distilled Water 45.0%
E~~AMP E 4 L
_ 2.0%
Kappa Carrageenan _ 3.0%
Iota Carrageenan Modified Starch 20%
Ratio of starchaotal 4:1 carrageenan Sorbitol SpecialTM 35.0%
Titanium Dioxide O.S%
Distilled Water 39.5%
Kappa Carrageenan l.S%
Iota Carrageenan 2.5%
Modified Starch 20.0%
Ratio of starchaotal 5:1 carrageenan Calycerin (CTSP) 25.0/' Titanium Dioz~ide O.S%
Distilled Water 50.5/~
Kappa Carrageenan 1.S%
Iota Carrageenan 2.5%
Modified Starch 20.0!~
Ratio of starchaotal S:1 carra eenan Ii laltitol 25.0/~
Titanium I~io~~de 0.5/~
Distalled Water SO.SlQ
Kappa Carrageenan 1.5%
Iota Carrageenan 2.5%
Modified Starch 20.0%
Ratio of starchaotal 5:1 carry eenan Glycerin (LTSP) I2.5%
Sorbitol SpecialTM 12.5%
Titanium Dioxide 0.5%
Distilled Water 50.5%
XAMPL
_ I .5%
Kap a Carry eenan _ 2.5%
Iota Carrageenan ~
Modified Starch 25.0%
Ratio of starchaotal 6.25:1 carrageenan Maltitol 5.0%
Sorbitol SpecialTM 15.0%
Titanium Dioxide 0.5%
Distilled Water 50.5%
_ EXAMFL E 9 Ka pa Carry eenan 2.5%
Iota Carrageenan 2.5%
Modified Starch 23.0%
Ratio of starchaotal 4~.6: I
carrageenan Maltitol 16%
Sorbitol S ecialTM ~%
Titanium Dioxide Distilled Water 4~10 Kappa Carry eenan 1.5/~
Iota Carrageenan ~.5%
T~~dilied Starcla 25.0/~
Ratio of starch:to~al 5:1 carry, een~n Maltitol 7.0!0 Sorbitol Special'~~ 13.0%
Tit~ni~am Dio~~ide 0010%
Distilled Water 4~.~0/~
1~
E~~AMPLE 11 Kappa Carrageenan l.S%
Iota Carrageenan 3.S%
Modified Starch 25.0%
Ratio of starchaotal 5:1 carrageenan Maltitol 8.0%
Sorbitol SpecialTM 15.0%
Titanium Dioxide 0.10%
Distilled Water 46.90%
Kap a Carrageenan 2.S% _ Iota Carra eenan 2.S%
Modified Starch 40.0%
Pregelatini~ed Starch 5.0%
Ratio of starchaotal 9:1 carrageenan Maltitol 3.75%
Sorbitol SpecialTM 18.75%
Titanium Dioxide Distilled Water 27.50!
The film-forming compositions of examples 1-12 were cast into films and dried to between about S°/~ and about 15°!~ moisture. 'The films were cut into strips 20 mm wide by SO mm long. The films for Examples 2-12 were tested for tensile strength at rupture and extensibility using a TA-XT2 Texture P~nnaly~er manufactured by Stable Micro Systems, (Surrey, UK). The following table charts the tensile strength and extensibility of the resulting films, where the values are mean values with standard deviations taken from four
(4) replicates.
Example # Tensile Strength at RuptureMaximum Extension at Rupture 1v mm 2 10.70.2 53.13.3 3 14.80.7 63.64.7 4 12.90.5 45.72.1
Example # Tensile Strength at RuptureMaximum Extension at Rupture 1v mm 2 10.70.2 53.13.3 3 14.80.7 63.64.7 4 12.90.5 45.72.1
5.810.4 43.2 ~ 1.6
6 13.2 ~ 1.2 51.4 ~ 2.2
7 ~ 7.10.6 45.98.3
8 15.62.4 64.95.7
9 10.30.3 42.42.2 29.72.0 56.62.0 11 18.7 ~ 4.5 41.4 ~ 9.2 12 29.50.6 59.87.2 To demonstrate the desirable characteristics for kappa carrageenan, iota carrageenan and bulking agents used in this invention, commercially available kappa S carrageenan, iota carrageenan and a modified starch were formed into solutions and their viscosity, gel point, m elting point a nd g el s trength w ere m easured. The m aterials used were as follows:
Kappa Carrageenan: Colloid 710I-I (L,ot # 1025) from TIC CTums of
Kappa Carrageenan: Colloid 710I-I (L,ot # 1025) from TIC CTums of
10 Belcamp I 1~.
Iota Carrageenan: Colloid 881Ie4 (Lot # 1539) from TIC Gums of ~elcamp
Iota Carrageenan: Colloid 881Ie4 (Lot # 1539) from TIC Gums of ~elcamp
11~.
Modified Starch (starch sodium octenyl succinate): N-Lok (Lot # FI~17502) from I~tational Starch ~c Chemical Co. of Bridgewater, I~ew Jersey.
In one proced~ar~~ for pxo~lun~ig~g ~ $~Iaa~-fc~rb~~ia~g co~~~pe~~i~ic~n lil .o that d~~~xi(a;~d above a 3~/~ dispersion of c~ax~ageenan in purified distilled vaster vas prepared by heating the v~~ter to 70°C and adding the c~xra~geea~an e~~ith stirring. The dispersion was heated at 70°C until it became smootla end free of any particul~.tes (non-dispersed carrageenan).
Similarly, a 10~/~ dispersion of modified starch in water was prepared.
'The viscosity, gelling, holding, frequency and heating (melting) profiles were measured using a mechanical rheometer (AR1000 Advanced lVlechanical Rheometer manufactured by 'lA Instruments ofNew Castle, Delaware) using a 4°
steel corn;.
Viscosity was measured by shearing the sample at a rate of 0 to 120 per second in two (2) minutes.
The gelling profile was determined by dropping the temperature from ~0°C to 10°C
at 5°C per minute, with constant strain and frequency of 2% and lHz, respectively. The gelling point was determined to be the temperature at which the storage and loss moduli, G' and G" respectively, crossed. Following gelling, the sample was held at 10°C for 5 min to obtain a holding profile. After the holding step, the mechanical spectrum (frequency profile) of the gel formed was determined by performing a frequency sweep from 0.lHz to 100Hz at 10°C, with constant strain of 2%. The storage modulus (G ~ at a frequency of 1Hz was chosen as the gel strength of the gel formed by the carrageenan dispersion. The gel was then heated at a rate of 5°C per minute from 10°C to 95°C to obtain the melting profile of the gel, with constant strain and frequency of 2% and lHz, respectively. The melting point was determined to be the temperature at which the storage and loss moduli, G' and G" respectively, crossed. The results are set forth in Table 2.
~anaple ~n~e~~aty ~ella~ag l~el~ng C~el ~treaagtln point p~ang cl~ C ~~ a 3% kappa carrageenan dis ersion in water61 g.4- 40.6 60.3 35,740 3% iota carrageenan dispersion in water93.8 61.2 64.9 976 1.5/~ kappa carrageenan +
1.5/~ iota carrageenan206.6 47.2 70.g 19,00 dispersion in water 10/~ starch sodium octenyl succinate 3.~ - - -The abcave results acre within the desirable ranges f~r o~iscositg$, gel point, aneltin g point and gel strength for iota carrageenan, kappa carrageenan and a b~all~ing agent.
preferably, the range for these parmneters for dispersions of iota carragoenan9 lgappa.
carrageenan and a bullring agent as described above are as set forth beloev in Table 3.
Sample Viscosity Gelling Melting Gel Strength point point cP C C a 3% kappa carrageenan_ dis ersion in water580 - 650 38 - 43 57 - 64 33,000 -38,000 3% iota carrageenan dispersion in water85 - 100 58 - 65 60 - 69 920 - 1,100 1.5% kappa carrageenan +
1.5% iota carrageenan190 - 220 44 - 50 67 - 75 18,000 -21,000 dispersion in water 10% starch sodium octenyl succinate 3 - S - - -The invention also includes a method for producing an edible non-gelatin film in accordance with the invention that is particularly adapted for high-volume production.
S Figure 1 is a flow chart of one embodiment of a such a method. Constituent ingredients of a non-gelatin film-forming composition comprising carrageenan are mixed 10 together with a high water content. The term "high water content" as used herein means a total water content that permits complete hydration of the hydrocolloid and allows the mass to have a viscosity of less than about 100,000 cP at a temperature less than about 100 degrees C. preferably the viscosity of the "wet" f Im-forming composition is less than about 50,000 cP, and most preferably the viscosity is less than about 10,000 cP. A water content of at least about 40 percent by weight has been shown to provide film-forming compositions having preferably low viscosities. The mixture is heated 20 to a viscous molten state. The molten film-forming composition is then at least partially dried 30 such that the moisture content of the falm-forming composition is substantially reduced to a low moisture content. 'The term "low water content" as used herein means the material produced by the process is sufficiently dry to produce a film that is the proper strength and da~te~2~il~ailit~,~ to be ~a~c~I iai .~ ~~pical_ enfap~~~latior~ process. ~
~~:.~atQr contea~E of~ah~a~~t 2~
percent or less b~~ weight has been shown to produce a useful film according to one '20 emb~diment of the process. ~ dried portion of the elm-forming composition is formed into a an edible non-gel~ti~a film such ass by e~itrusion, rolling, or any other suitable method..
Table 1 lists the ingredients of one embodiment of a mixture for use in a process according to the invention as shown in Figure 1.
TABLE 4.
Ingredient Approximate Weight Percent Kappa carrageenan I _S
Iota carrageenan 4 Modified starch 22.2 Sorbitol Special~ 9.9 Lycasin~ 4.4 Glycerin 5.4 Distilled Water . 49.4 Additional Distilled Water3.2 ~ther formulas comprising at least one film-forming hydrocolloid, at least one plastici~er, and water may be used in a process according to the invention v~ithout departing from the invention.
The kappa carrageenan may be TIC hretested~ C~LL~ID 710H, and the iota carrageenan may be TIC Pretested~ C~LL~ID ~~1M, both available from TIC Gums of >3elcamp, Maryland. °The modified starch may be Grain Processing Company No. )3-793.
Sorbitol, especially non-crystallising sorbitol (such as Sorbitol Specials available from SPI Polol), maltitol syrup (such as Lycasin~), and glycerin may be used as plastici~ers, either alone or in combination. ~ther equivalent ingredients may be substituted.
~'referal~ly, tlbe w~ad~r i~ ptaxi~~d distilled ;v;~ter.
In one embodiment of tlae process, miming the ingredients includes pre-miming all liqa~id components ex=cept for a portion of the ~vatc;r and glyceria~ by hand in a container.
The mused liquid components are then preheated to about 200 degrees h. The dryr ingredients (the carrageenan and modified starch) are added to the pre-mixed liquid ingredients. The ingredients are mixed together and heated under an applied vacuum to form a molten film-forming composition. In one embodiment, the liquid and dry ingredients are mixed in a double planetary mixer at about 35 RPM for about fifteen minutes. The mixer speed is then reduced to about 20 RPM and a vacuum of 20 inches hg.
is applied to the mass for agitation during the melting process. The mass is then further mixed and melted under pressure for about 2.5 hours at a pressure of about 15 inches Hg.
The applied pressure acts to eliminate trapped air during the mixing and melting process.
The vacuum is released and the additional water, glycerin, and colorants (if any) are added to the mixture. The vacuum is reapplied at 15 inches Hg, and the mass is continually mixed at an elevated temperature for about 1 hour. The mixture is then stored at an elevated temperature. Irt one embodiment, the mixture is stored at a temperature of about 1 ~5 degrees F. The prepared "wet" film-forming composition has a viscosity of less than about 100,000 centa-Poise as measured at 90°C using a mechanical rheometer at a shear rate of 0 to 100 per second in two (2) minutes, a Brookfield viscometer, or other device known to practitioners in the art to measure viscosity. Preferably, the "wet"
film-forming composition has a viscosity less than about 50,000 cP. More preferably, the "wet" film-forming composition has a viscosity less than about 10,000 cP. The "wet" film-forming composition can be used immediately. Alternatively, the ":wet" composition can be cooled to room temperature and stored as a gelled mass. The solidified gel mass can be cut into segments, remelted into a molten state, and introdueed into the process at a later time.
The prepared molten film-forming composition is then dried to a low water content.
For example, the water content may be reduced from at least about 40 percent by weight to less than or equal to about 30 percent by weight. In a particular embodiment, an initial water content of about 57 weight percent is reduced to about 16.5 percent.
Reducing the water content to about 16.5 percent by weight yields a dried film-forming composition that can be readily formed into an edible elastic film that can be used to enrobe and encapsulate oral dosage forms using known encapsulation methods. A usable non-gelatin film produced ~cc~arding to ~ l~roc~~~~; ia~ accordance ~%ith the an~eratioa~ nbay hare a te~~~il~
strength at rupture of at least about 5 i~T at room temperature. such a usable tlm n my also have a~ percent elongation of at lest about 50 percent ~ rupteare at room temperature.
Continuous agitation and mixing of the film-forming composition during dr~Fing ma3~ be used to facilitate uniform drying and consistency of the material. The film-forming composition may be heated to between about 210 and about 2~0 degrees F under a pressure of about 1-29 inches hg vacuum during drying.
The dried portion of the film-forming composition is formed into a filnf:' This may be accomplished by passing the dried material through a film-forming device.
In one embodiment, the dried portion of the film-forming composition is extruded through a fiIm-forming die to form a film that is about 6 inches wide and about .025 inch thick. Films having different widths or thicknesses may be produced in a similar or other suitable manner. The formed film then may be cooled such as by passing the hot film over a chilled setting drum, blowing chilled air over the hot film, or the like. The cooled and set film material then may be passed to an encapsulation or enrobement device for encapsulating or enrobing oral dosage forms.
Figure 2 shows one embodiment of an apparatus I00 that can be used to produce an edible film according to the process described above. In this embodiment, the film-forming composition is substantially fully mixed and heated in a mixer I 10.
The mixer 1 I O may be a double planetary mixer such as a Ross Model No. HDM 40. The mixed f lm-forming composition is then delivered to a heated supply tank 120. The supply tank I20 I S includes a heating device capable of heating the f Im-forming composition to a temperature of about I ~5 degrees F and maintaining the mass at such temperature.
Conduits I25, 135 connect the supply tank 120 to the inlet end 142 of an extruder/dryer I40. A metering pump I30 can draw portions of the molten film-forming composition from the supply tank 120 through conduit 125 and pump the material at a metered rate to the extruder/dryer I40 through conduit 135. The metering pump 130 may be a Zenith metering gear pump that is capable of delivering the film-forming composition to the extruder/dryer I40 at a metered rate of about 12.5 liters per hour, for example. The extruder/dryer 140 includes a barrel portion 143 and a drive unit 141.
In the embodiment shown in Figure 3, the extruder/dryer I4~0 includes co-rotating tvv~in screws 149 (one screw is shown) in an elongated barrel 143. 'The screws 149 of the eacta~ad~r/db~ ~x 1a0 are cc~a~figa~red ~2~ch that the hlm-f~aa-aaiing material is ~aaa~ged fr~rn the inlet end 142 to the outlet end 1~=4~ of the e~truder/dryer as the screws I4~9 axe syzachronouslg~ rotated by the drive unit I41. 'The screws I49 also are c~nfigured to agitate and mica the elm-forming rxaaterial ass it passes through the e~.struder/drg~e.r 140. In one;
embodiment of the apparatus 100, the screws 149 are about 5~ mm in diameter and the screws 149 rotate at about 90 rpm. In this embodiment, the barrel portion of the extruder/dryer 140 is about 1.1 meters in length.
The extruder/dryer 140 may include a series of individually controllabl2'heating zones along its length. One or more heaters in each zone may be controlled by a suitable automatic controller 190 with temperature sensors as required. In one embodiment of the apparatus, the film-forming composition is heated to a temperature of about 270 degrees F
in a first zone (proximate to the inlet end 142), to about 280 degrees F in a second zone, to about 245 degrees F in a third zone, and to about 242 degrees in a fourth zone (proximate to the outlet end 144). In this embodiment, the dried film-forming composition exits the extruder/dryer 140 at about 240 degrees F.
As the film-forming composition is heated and agitated in the extruder/dryer 140, water is extracted from the film-forming composition through at least one water extraction port 146, 147, and/or 148. In the embodiment shown in Figures 2 and 3, the extruder/dryer 140 includes three water extraction ports 146, 147, 148. Two water extraction ports 14b, 147 are provided in zone 2 of the extruder/dryer 140, and a third water extraction port 148 is provided in zone 3 as shown in Figure 3. More or fewer water extraction ports may be used at various positions along the barrel portion 143 of the extruder/dryer 140. In one embodiment of the apparatus 100, the third water extraction port 148 is capped and is not used. In this embodiment, a vacuum of about 20 inches Hg is applied at the first extraction port 146, and a vacuum of about 21 inches Hg is applied at the second extraction port 147.
The vacuum applied at the water extraction ports 146, 147, 148 should be optimized to effectively extract water vapor from the extruder/dryer 140 without also extracting portions of the film-forning composition from the extruder/dryer 140.
~nce the film-forming composition is dried to less than about 25 weight percent water, the film-forming composition is passed from the extruder/dryer 140 to a film-forming device 150, as shown in Figure 2. In one embodiment, the film-forming device 1S0 is an ea~ttrusion die. A dried portion of the film-forming composition may be supplied directly froraa the e~~tru~ler/d~,~er 1'Q to an e~~trusao~a die 109 a~ ~hov~rn in ('figure 4.
Alternatively, ~, dried portion of the filrra-forming compo; ition may be stored and formed into a film at ~ later time. In one embodiment, an e~gtx-usion die life that shown in Figure 4 is c.~n~gdared to exude a ribbon of edible iilrn 1 ~2 that is ~b~~at 6 itmhes wide said about .025 inch thicl~. 'The die 150 includes a lower portion 158 and a top portion 15~. The film-forming material enters the die 150 through an inlet 154 and exits the die through an outlet 156. The film-forming material is shaped into a ribbon of f lm as the material is forced through an extrusion channel 153. Other dies that extrude films having differed widths and/or thicknesses may also be used. The apparatus 100 may also include a splitting device 200 like that shown in Figure 2 for splitting the ribbon 152 into two or more separate ribbons of film material. Alternately, a divider at the outlet of the extrusion die may split the film into separate ribbons. In Figure 4, the ribbon 152 is divided by the splitting device into a first ribbon portion 152a, and a second ribbon portion 152b.
In order to cool and stabilize the extruded film 152, the film 152 may be passed over a chilled setting drum 160 or otherwise cooled as shown in Figure 2. The film 152 can then be fed directly to an encapsulation or enrobement device 500 for encapsulating or I O enrobing oral dosage forms in the film 152. For example, the film 152 may be directed to a pair of cooperating rotary dies for encapsulating or enrobing dosage forms in portions of the film 152 (not shown). Encapsulation or enrobement devices like those currently used to encapsulate and/or enrobe oral dosage forms in gelatin-based film materials can be used.
Figure 5 shows an embodiment of a liquid-filled oral dosage form 200 having first 15 and second shell portions 220, 230 formed of an edible non-gelatin film 152 produced by the process and/or apparatus described above. The dosage form 200 includes a liquid fill material 210 encapsulated between a first shell portion 220 and a second shell portion 230.
The first and second shell portions 220, 230 are joined at a seam 240 encircling the dosage form 200. The oral dosage form 200 can be produced using known encapsulation methods 20 and equipment such as a rotary die process and apparatus.
An embodiment of a enu-obed tablet or caplet 300 having first and second shell portions 320, 330 comprising an edible non-gelatin film 152 produced by the process and/or apparatus described above is shown in Figure 6. '1 he dosage form 300 includes a substantially solid core 310 enrobed between a first shell portion 320 and a second shell 25 portion 330. °I'he fret and second shell portions 320, 330 substantially conform to the o~at~r :~la~pa of~l2r e.ore 310 ~,ad pro ~~~led together ~t a ~,~~am line 31-0 eaacircling the dosage form 300. Tlae oral dosage form 300 can be produced using l~zaovan enrobement methods and equipment such as a rotaa-~y die process end apparatus (not shoe~~n).
Once the non-gelatin film 152 has been applied to a dosage form 200 or 300, the 30 film 152 m~.y be farther dried to a substantially hard and glassy state.
For example, the applied film 152 may be finally dried to a water content of less than about 10 percent by weight by subjecting the applied film 152 to forced dry air.
Although specific embodiments of the present invention have been desc~'ibed in detail, it is to be expressly understood that the invention is not limited thereto. Th:e above detailed description of embodiments of the invention is provided for example only and should not be construed as limiting the invention. Modifications and substitutions will be apparent to those skilled in the art. All such modifications and substitutions are intended to be within the scope of the appended claims.
2~
Modified Starch (starch sodium octenyl succinate): N-Lok (Lot # FI~17502) from I~tational Starch ~c Chemical Co. of Bridgewater, I~ew Jersey.
In one proced~ar~~ for pxo~lun~ig~g ~ $~Iaa~-fc~rb~~ia~g co~~~pe~~i~ic~n lil .o that d~~~xi(a;~d above a 3~/~ dispersion of c~ax~ageenan in purified distilled vaster vas prepared by heating the v~~ter to 70°C and adding the c~xra~geea~an e~~ith stirring. The dispersion was heated at 70°C until it became smootla end free of any particul~.tes (non-dispersed carrageenan).
Similarly, a 10~/~ dispersion of modified starch in water was prepared.
'The viscosity, gelling, holding, frequency and heating (melting) profiles were measured using a mechanical rheometer (AR1000 Advanced lVlechanical Rheometer manufactured by 'lA Instruments ofNew Castle, Delaware) using a 4°
steel corn;.
Viscosity was measured by shearing the sample at a rate of 0 to 120 per second in two (2) minutes.
The gelling profile was determined by dropping the temperature from ~0°C to 10°C
at 5°C per minute, with constant strain and frequency of 2% and lHz, respectively. The gelling point was determined to be the temperature at which the storage and loss moduli, G' and G" respectively, crossed. Following gelling, the sample was held at 10°C for 5 min to obtain a holding profile. After the holding step, the mechanical spectrum (frequency profile) of the gel formed was determined by performing a frequency sweep from 0.lHz to 100Hz at 10°C, with constant strain of 2%. The storage modulus (G ~ at a frequency of 1Hz was chosen as the gel strength of the gel formed by the carrageenan dispersion. The gel was then heated at a rate of 5°C per minute from 10°C to 95°C to obtain the melting profile of the gel, with constant strain and frequency of 2% and lHz, respectively. The melting point was determined to be the temperature at which the storage and loss moduli, G' and G" respectively, crossed. The results are set forth in Table 2.
~anaple ~n~e~~aty ~ella~ag l~el~ng C~el ~treaagtln point p~ang cl~ C ~~ a 3% kappa carrageenan dis ersion in water61 g.4- 40.6 60.3 35,740 3% iota carrageenan dispersion in water93.8 61.2 64.9 976 1.5/~ kappa carrageenan +
1.5/~ iota carrageenan206.6 47.2 70.g 19,00 dispersion in water 10/~ starch sodium octenyl succinate 3.~ - - -The abcave results acre within the desirable ranges f~r o~iscositg$, gel point, aneltin g point and gel strength for iota carrageenan, kappa carrageenan and a b~all~ing agent.
preferably, the range for these parmneters for dispersions of iota carragoenan9 lgappa.
carrageenan and a bullring agent as described above are as set forth beloev in Table 3.
Sample Viscosity Gelling Melting Gel Strength point point cP C C a 3% kappa carrageenan_ dis ersion in water580 - 650 38 - 43 57 - 64 33,000 -38,000 3% iota carrageenan dispersion in water85 - 100 58 - 65 60 - 69 920 - 1,100 1.5% kappa carrageenan +
1.5% iota carrageenan190 - 220 44 - 50 67 - 75 18,000 -21,000 dispersion in water 10% starch sodium octenyl succinate 3 - S - - -The invention also includes a method for producing an edible non-gelatin film in accordance with the invention that is particularly adapted for high-volume production.
S Figure 1 is a flow chart of one embodiment of a such a method. Constituent ingredients of a non-gelatin film-forming composition comprising carrageenan are mixed 10 together with a high water content. The term "high water content" as used herein means a total water content that permits complete hydration of the hydrocolloid and allows the mass to have a viscosity of less than about 100,000 cP at a temperature less than about 100 degrees C. preferably the viscosity of the "wet" f Im-forming composition is less than about 50,000 cP, and most preferably the viscosity is less than about 10,000 cP. A water content of at least about 40 percent by weight has been shown to provide film-forming compositions having preferably low viscosities. The mixture is heated 20 to a viscous molten state. The molten film-forming composition is then at least partially dried 30 such that the moisture content of the falm-forming composition is substantially reduced to a low moisture content. 'The term "low water content" as used herein means the material produced by the process is sufficiently dry to produce a film that is the proper strength and da~te~2~il~ailit~,~ to be ~a~c~I iai .~ ~~pical_ enfap~~~latior~ process. ~
~~:.~atQr contea~E of~ah~a~~t 2~
percent or less b~~ weight has been shown to produce a useful film according to one '20 emb~diment of the process. ~ dried portion of the elm-forming composition is formed into a an edible non-gel~ti~a film such ass by e~itrusion, rolling, or any other suitable method..
Table 1 lists the ingredients of one embodiment of a mixture for use in a process according to the invention as shown in Figure 1.
TABLE 4.
Ingredient Approximate Weight Percent Kappa carrageenan I _S
Iota carrageenan 4 Modified starch 22.2 Sorbitol Special~ 9.9 Lycasin~ 4.4 Glycerin 5.4 Distilled Water . 49.4 Additional Distilled Water3.2 ~ther formulas comprising at least one film-forming hydrocolloid, at least one plastici~er, and water may be used in a process according to the invention v~ithout departing from the invention.
The kappa carrageenan may be TIC hretested~ C~LL~ID 710H, and the iota carrageenan may be TIC Pretested~ C~LL~ID ~~1M, both available from TIC Gums of >3elcamp, Maryland. °The modified starch may be Grain Processing Company No. )3-793.
Sorbitol, especially non-crystallising sorbitol (such as Sorbitol Specials available from SPI Polol), maltitol syrup (such as Lycasin~), and glycerin may be used as plastici~ers, either alone or in combination. ~ther equivalent ingredients may be substituted.
~'referal~ly, tlbe w~ad~r i~ ptaxi~~d distilled ;v;~ter.
In one embodiment of tlae process, miming the ingredients includes pre-miming all liqa~id components ex=cept for a portion of the ~vatc;r and glyceria~ by hand in a container.
The mused liquid components are then preheated to about 200 degrees h. The dryr ingredients (the carrageenan and modified starch) are added to the pre-mixed liquid ingredients. The ingredients are mixed together and heated under an applied vacuum to form a molten film-forming composition. In one embodiment, the liquid and dry ingredients are mixed in a double planetary mixer at about 35 RPM for about fifteen minutes. The mixer speed is then reduced to about 20 RPM and a vacuum of 20 inches hg.
is applied to the mass for agitation during the melting process. The mass is then further mixed and melted under pressure for about 2.5 hours at a pressure of about 15 inches Hg.
The applied pressure acts to eliminate trapped air during the mixing and melting process.
The vacuum is released and the additional water, glycerin, and colorants (if any) are added to the mixture. The vacuum is reapplied at 15 inches Hg, and the mass is continually mixed at an elevated temperature for about 1 hour. The mixture is then stored at an elevated temperature. Irt one embodiment, the mixture is stored at a temperature of about 1 ~5 degrees F. The prepared "wet" film-forming composition has a viscosity of less than about 100,000 centa-Poise as measured at 90°C using a mechanical rheometer at a shear rate of 0 to 100 per second in two (2) minutes, a Brookfield viscometer, or other device known to practitioners in the art to measure viscosity. Preferably, the "wet"
film-forming composition has a viscosity less than about 50,000 cP. More preferably, the "wet" film-forming composition has a viscosity less than about 10,000 cP. The "wet" film-forming composition can be used immediately. Alternatively, the ":wet" composition can be cooled to room temperature and stored as a gelled mass. The solidified gel mass can be cut into segments, remelted into a molten state, and introdueed into the process at a later time.
The prepared molten film-forming composition is then dried to a low water content.
For example, the water content may be reduced from at least about 40 percent by weight to less than or equal to about 30 percent by weight. In a particular embodiment, an initial water content of about 57 weight percent is reduced to about 16.5 percent.
Reducing the water content to about 16.5 percent by weight yields a dried film-forming composition that can be readily formed into an edible elastic film that can be used to enrobe and encapsulate oral dosage forms using known encapsulation methods. A usable non-gelatin film produced ~cc~arding to ~ l~roc~~~~; ia~ accordance ~%ith the an~eratioa~ nbay hare a te~~~il~
strength at rupture of at least about 5 i~T at room temperature. such a usable tlm n my also have a~ percent elongation of at lest about 50 percent ~ rupteare at room temperature.
Continuous agitation and mixing of the film-forming composition during dr~Fing ma3~ be used to facilitate uniform drying and consistency of the material. The film-forming composition may be heated to between about 210 and about 2~0 degrees F under a pressure of about 1-29 inches hg vacuum during drying.
The dried portion of the film-forming composition is formed into a filnf:' This may be accomplished by passing the dried material through a film-forming device.
In one embodiment, the dried portion of the film-forming composition is extruded through a fiIm-forming die to form a film that is about 6 inches wide and about .025 inch thick. Films having different widths or thicknesses may be produced in a similar or other suitable manner. The formed film then may be cooled such as by passing the hot film over a chilled setting drum, blowing chilled air over the hot film, or the like. The cooled and set film material then may be passed to an encapsulation or enrobement device for encapsulating or enrobing oral dosage forms.
Figure 2 shows one embodiment of an apparatus I00 that can be used to produce an edible film according to the process described above. In this embodiment, the film-forming composition is substantially fully mixed and heated in a mixer I 10.
The mixer 1 I O may be a double planetary mixer such as a Ross Model No. HDM 40. The mixed f lm-forming composition is then delivered to a heated supply tank 120. The supply tank I20 I S includes a heating device capable of heating the f Im-forming composition to a temperature of about I ~5 degrees F and maintaining the mass at such temperature.
Conduits I25, 135 connect the supply tank 120 to the inlet end 142 of an extruder/dryer I40. A metering pump I30 can draw portions of the molten film-forming composition from the supply tank 120 through conduit 125 and pump the material at a metered rate to the extruder/dryer I40 through conduit 135. The metering pump 130 may be a Zenith metering gear pump that is capable of delivering the film-forming composition to the extruder/dryer I40 at a metered rate of about 12.5 liters per hour, for example. The extruder/dryer 140 includes a barrel portion 143 and a drive unit 141.
In the embodiment shown in Figure 3, the extruder/dryer I4~0 includes co-rotating tvv~in screws 149 (one screw is shown) in an elongated barrel 143. 'The screws 149 of the eacta~ad~r/db~ ~x 1a0 are cc~a~figa~red ~2~ch that the hlm-f~aa-aaiing material is ~aaa~ged fr~rn the inlet end 142 to the outlet end 1~=4~ of the e~truder/dryer as the screws I4~9 axe syzachronouslg~ rotated by the drive unit I41. 'The screws I49 also are c~nfigured to agitate and mica the elm-forming rxaaterial ass it passes through the e~.struder/drg~e.r 140. In one;
embodiment of the apparatus 100, the screws 149 are about 5~ mm in diameter and the screws 149 rotate at about 90 rpm. In this embodiment, the barrel portion of the extruder/dryer 140 is about 1.1 meters in length.
The extruder/dryer 140 may include a series of individually controllabl2'heating zones along its length. One or more heaters in each zone may be controlled by a suitable automatic controller 190 with temperature sensors as required. In one embodiment of the apparatus, the film-forming composition is heated to a temperature of about 270 degrees F
in a first zone (proximate to the inlet end 142), to about 280 degrees F in a second zone, to about 245 degrees F in a third zone, and to about 242 degrees in a fourth zone (proximate to the outlet end 144). In this embodiment, the dried film-forming composition exits the extruder/dryer 140 at about 240 degrees F.
As the film-forming composition is heated and agitated in the extruder/dryer 140, water is extracted from the film-forming composition through at least one water extraction port 146, 147, and/or 148. In the embodiment shown in Figures 2 and 3, the extruder/dryer 140 includes three water extraction ports 146, 147, 148. Two water extraction ports 14b, 147 are provided in zone 2 of the extruder/dryer 140, and a third water extraction port 148 is provided in zone 3 as shown in Figure 3. More or fewer water extraction ports may be used at various positions along the barrel portion 143 of the extruder/dryer 140. In one embodiment of the apparatus 100, the third water extraction port 148 is capped and is not used. In this embodiment, a vacuum of about 20 inches Hg is applied at the first extraction port 146, and a vacuum of about 21 inches Hg is applied at the second extraction port 147.
The vacuum applied at the water extraction ports 146, 147, 148 should be optimized to effectively extract water vapor from the extruder/dryer 140 without also extracting portions of the film-forning composition from the extruder/dryer 140.
~nce the film-forming composition is dried to less than about 25 weight percent water, the film-forming composition is passed from the extruder/dryer 140 to a film-forming device 150, as shown in Figure 2. In one embodiment, the film-forming device 1S0 is an ea~ttrusion die. A dried portion of the film-forming composition may be supplied directly froraa the e~~tru~ler/d~,~er 1'Q to an e~~trusao~a die 109 a~ ~hov~rn in ('figure 4.
Alternatively, ~, dried portion of the filrra-forming compo; ition may be stored and formed into a film at ~ later time. In one embodiment, an e~gtx-usion die life that shown in Figure 4 is c.~n~gdared to exude a ribbon of edible iilrn 1 ~2 that is ~b~~at 6 itmhes wide said about .025 inch thicl~. 'The die 150 includes a lower portion 158 and a top portion 15~. The film-forming material enters the die 150 through an inlet 154 and exits the die through an outlet 156. The film-forming material is shaped into a ribbon of f lm as the material is forced through an extrusion channel 153. Other dies that extrude films having differed widths and/or thicknesses may also be used. The apparatus 100 may also include a splitting device 200 like that shown in Figure 2 for splitting the ribbon 152 into two or more separate ribbons of film material. Alternately, a divider at the outlet of the extrusion die may split the film into separate ribbons. In Figure 4, the ribbon 152 is divided by the splitting device into a first ribbon portion 152a, and a second ribbon portion 152b.
In order to cool and stabilize the extruded film 152, the film 152 may be passed over a chilled setting drum 160 or otherwise cooled as shown in Figure 2. The film 152 can then be fed directly to an encapsulation or enrobement device 500 for encapsulating or I O enrobing oral dosage forms in the film 152. For example, the film 152 may be directed to a pair of cooperating rotary dies for encapsulating or enrobing dosage forms in portions of the film 152 (not shown). Encapsulation or enrobement devices like those currently used to encapsulate and/or enrobe oral dosage forms in gelatin-based film materials can be used.
Figure 5 shows an embodiment of a liquid-filled oral dosage form 200 having first 15 and second shell portions 220, 230 formed of an edible non-gelatin film 152 produced by the process and/or apparatus described above. The dosage form 200 includes a liquid fill material 210 encapsulated between a first shell portion 220 and a second shell portion 230.
The first and second shell portions 220, 230 are joined at a seam 240 encircling the dosage form 200. The oral dosage form 200 can be produced using known encapsulation methods 20 and equipment such as a rotary die process and apparatus.
An embodiment of a enu-obed tablet or caplet 300 having first and second shell portions 320, 330 comprising an edible non-gelatin film 152 produced by the process and/or apparatus described above is shown in Figure 6. '1 he dosage form 300 includes a substantially solid core 310 enrobed between a first shell portion 320 and a second shell 25 portion 330. °I'he fret and second shell portions 320, 330 substantially conform to the o~at~r :~la~pa of~l2r e.ore 310 ~,ad pro ~~~led together ~t a ~,~~am line 31-0 eaacircling the dosage form 300. Tlae oral dosage form 300 can be produced using l~zaovan enrobement methods and equipment such as a rotaa-~y die process end apparatus (not shoe~~n).
Once the non-gelatin film 152 has been applied to a dosage form 200 or 300, the 30 film 152 m~.y be farther dried to a substantially hard and glassy state.
For example, the applied film 152 may be finally dried to a water content of less than about 10 percent by weight by subjecting the applied film 152 to forced dry air.
Although specific embodiments of the present invention have been desc~'ibed in detail, it is to be expressly understood that the invention is not limited thereto. Th:e above detailed description of embodiments of the invention is provided for example only and should not be construed as limiting the invention. Modifications and substitutions will be apparent to those skilled in the art. All such modifications and substitutions are intended to be within the scope of the appended claims.
2~
Claims (223)
1. A method of producing a non-gelatin film, the method comprising:
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition comprising at least 40 percent water by weight;
(b) extracting a portion of the water from the film-forming composition to form a dried portion having a water content of less than or equal to 25 percent by weight; and (c) forming the dried portion of the film-forming composition into a film.
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition comprising at least 40 percent water by weight;
(b) extracting a portion of the water from the film-forming composition to form a dried portion having a water content of less than or equal to 25 percent by weight; and (c) forming the dried portion of the film-forming composition into a film.
2. A method according to claim 1 wherein combining includes mechanically mixing the hydrocolloid, the water, and the plasticizer.
3. A method according to claim 1 wherein combining includes heating the hydrocolloid, the water, and the plasticizer as they are combined.
4. A method according to claim 1, the method further comprising agitating and heating the film-forming composition as water is extracted.
5. A method according to claim 4 wherein the method further comprises agitating and heating the film-forming composition under pressure.
6. A method according to claim 1 wherein the film-forming composition further comprises a bulking agent.
7. A method according to claim 6 wherein the bulking agent comprises at least one starch ether or at least one esterified starch.
8. A method according to claim 1 wherein the at least one plasticizer is selected from the group consisting of sorbitol, maltitol, and glycerin.
9. A method according to claim 1 wherein the hydrocolloid is selected from the group consisting of carrageenan, alginates, agar, guar, pectin, locust bean gum, xanthan gum, starch, and gellan gum.
10. A method according to claim 1 wherein the hydrocolloid comprises carrageenan.
11. A method according to claim 10 wherein the carrageenan comprises iota carrageenan.
12. A method according to claim 11 wherein the iota carrageenan comprises 1-15 percent by weight of the film-forming composition.
13. A method according to claim 11 wherein the iota carrageenan comprises 3-8 percent by weight of the film-forming composition.
14. A method according to claim 10 wherein the carrageenan comprises kappa carrageenan.
15. A method according to claim 14 wherein the kappa carrageenan comprises 0.5-percent by weight of the film-forming composition.
16. A method according to claim 14 wherein the kappa carrageenan comprises 1-5 percent by weight of the film-forming composition.
17. A method according to claim 1 wherein the film-forming composition comprises:
(a) 3-9 weight percent carrageenan;
(b) 5-35 weight percent plasticizer; and (c) at least 40 weight percent water.
(a) 3-9 weight percent carrageenan;
(b) 5-35 weight percent plasticizer; and (c) at least 40 weight percent water.
18. A method according to claim 17 wherein the film-forming composition further comprises 10-40 weight percent bulking agent.
19. A method according to claim 18 wherein the bulking agent comprises starch.
20. A method according to claim 17 wherein the plasticizer comprises glycerin.
21. A method according to claim 17 wherein the plasticizer comprises sorbitol syrup.
22. A method according to claim 17 wherein the plasticizer comprises maltitol syrup.
23 A method according to claim 1 wherein the film-forming composition comprises:
(a) 4-10 weight percent carrageenan;
(b) 10-40 weight percent starch;
(c) 5-35 weight percent plasticizer; and (d) at least 40 weight percent water.
(a) 4-10 weight percent carrageenan;
(b) 10-40 weight percent starch;
(c) 5-35 weight percent plasticizer; and (d) at least 40 weight percent water.
24. A method according to claim 23 wherein the carrageenan comprises:
(a) 1-4 weight percent kappa carrageenan; and (b) 3-8 weight percent iota carrageenan.
(a) 1-4 weight percent kappa carrageenan; and (b) 3-8 weight percent iota carrageenan.
25. A method according to claim 1 wherein the dried portion of the film-forming composition comprises 8-25 percent water by weight.
26. A method according to claim 1 wherein the film-forming composition is preheated to 180-210 degrees Fahrenheit before water is extracted from the composition.
27. A method according to claim 1 wherein the film-forming composition has a viscosity less than 100,000 cP as measured at a temperature less than 100 degrees C.
28. A method according to claim 1 wherein the film-forming composition is heated under pressure to a temperature of at least 210 degrees Fahrenheit as water is extracted from the composition.
29. A method according to claim 28 wherein the pressure is 1-29 inches Hg.
30. A method according to claim 28 wherein the film-forming composition is heated to a temperature of 240-280 degrees Fahrenheit as water is extracted from the composition.
31. A method according to claim 1 wherein extracting water from the film-forming composition includes passing the film-forming composition through an extruder/dryer.
32. A method according to claim 31 further comprising agitating the film-forming composition between cooperating rotating twin screws in the extruder/dryer as water is extracted.
33. A method according to claim 1 wherein forming the dried portion of the film-forming composition into a film includes extruding the dried portion through a film-forming die.
34. A method according to claim 1 wherein extracting water from the film-forming composition includes extracting water vapor from the composition by heating the composition and applying a vacuum.
35. A method according to claim 1 wherein the formed film has a tensile strength at rupture of at least 0.4 Newtons per square millimeter (N/mm2) at room temperature.
36. A method according to claim 1 wherein the formed film has a percent elongation of at least 50 percent at rupture at room temperature.
37. A method according to claim 1 wherein the film-forming composition has a viscosity of less than 100,000 cP as measured at a temperature less than 100 degrees C.
38. A method of producing a non-gelatin film, the method comprising:
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition having a water content of at least 40 percent by weight;
(b) extracting a portion of the water from the film-forming composition to form a dried portion; and (c) forming the dried portion of the film-forming composition into a film without extracting a substantial additional portion of the water during formation of the film, wherein the formed film has a tensile strength at rupture of at least 0.4 N/mm2 at room temperature.
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition having a water content of at least 40 percent by weight;
(b) extracting a portion of the water from the film-forming composition to form a dried portion; and (c) forming the dried portion of the film-forming composition into a film without extracting a substantial additional portion of the water during formation of the film, wherein the formed film has a tensile strength at rupture of at least 0.4 N/mm2 at room temperature.
39. A method according to claim 38 wherein combining includes mechanically mixing the hydrocolloid, the water, and the plasticizer.
40. A method according to claim 38 wherein combining includes heating the hydrocolloid, the water, and the plasticizer as they are combined.
41. A method according to claim 38, the method further comprising agitating and heating the film-forming composition as water is extracted.
42. A method according to claim 41 wherein the method further comprises agitating and heating the film-forming composition under pressure.
43. A method according to claim 38 wherein the film-forming composition further comprises a bulking agent.
44. A method according to claim 43 wherein the bulking agent comprises at least one starch ether or at least one esterified starch.
45. A method according to claim 38 wherein the at least one plasticizer is selected from the group consisting of sorbitol, maltitol, and glycerin.
46. A method according to claim 38 wherein the hydrocolloid is selected from the group consisting of carrageenan, alginates, agar, guar, pectin, locust bean gum, xanthan gum, starch, and gellan gum.
47. A method according to claim 38 wherein the hydrocolloid comprises carrageenan.
48. A method according to claim 47 wherein the carrageenan comprises iota carrageenan.
49. A method according to claim 48 wherein the iota carrageenan comprises 1-15 percent by weight of the film-forming composition.
50. A method according to claim 48 wherein the iota carrageenan comprises 3-8 percent by weight of the film-forming composition.
51. A method according to claim 47 wherein the carrageenan comprises kappa carrageenan.
52. A method according to claim 51 wherein the kappa carrageenan comprises 0.5-percent by weight of the film-forming composition.
53. A method according to claim 51 wherein the kappa carrageenan comprises 1-5 percent by weight of the film-forming composition.
54. A method according to claim 38 wherein the film-forming composition comprises:
(a) 3-9 weight percent carrageenan;
(b) 5-35 weight percent plasticizer; and (c) at least 40 weight percent water.
(a) 3-9 weight percent carrageenan;
(b) 5-35 weight percent plasticizer; and (c) at least 40 weight percent water.
55. A method according to claim 54 wherein the film-forming composition further comprises 10-40 weight percent bulking agent.
56. A method according to claim 55 wherein the bulking agent comprises starch.
57. A method according to claim 54 wherein the plasticizer comprises glycerin.
58. A method according to claim 54 wherein the plasticizer comprises sorbitol syrup.
59. A method according to claim 54 wherein the plasticizer comprises maltitol syrup.
60. A method according to claim 38 wherein the film-forming composition comprises:
(a) 4-10 weight percent carrageenan;
(b) 10-40 weight percent starch;
(c) 5-35 weight percent plasticizer; and (d) at least 40 weight percent water.
(a) 4-10 weight percent carrageenan;
(b) 10-40 weight percent starch;
(c) 5-35 weight percent plasticizer; and (d) at least 40 weight percent water.
61. A method according to claim 60 wherein the carrageenan comprises:
(a) 1-2 weight percent kappa carrageenan; and (b) 3-5 weight percent iota carrageenan.
(a) 1-2 weight percent kappa carrageenan; and (b) 3-5 weight percent iota carrageenan.
62. A method according to claim 38 wherein the dried portion of the film-forming composition comprises 8-25 percent water by weight.
63. A method according to claim 38 wherein the film-forming composition is preheated to 180-210 degrees Fahrenheit before water is extracted from the composition.
64. A method according to claim 38 wherein the film-forming composition has a viscosity less than 100,000 cP as measured at a temperature less than 100 degrees C.
65. A method according to claim 38 wherein the film-forming composition is heated under pressure to a temperature of at least 240 degrees as water is extracted from the composition.
66. A method according to claim 65 wherein the pressure is 1-29 inches Hg.
67. A method according to claim 65 wherein the film-forming composition is heated to a temperature of 240-280 degrees Fahrenheit as water is extracted from the composition.
68. A method according to claim 38 wherein extracting water from the film-forming composition includes passing the film-forming composition through an extruder/dryer.
69. A method according to claim 68 further comprising agitating the film-forming composition between cooperating rotating twin screws in the extruder/dryer as water is extracted.
70. A method according to claim 38 wherein forming the dried portion of the film-forming composition into a film includes extruding the dried portion through a film-forming die.
71. A method according to claim 38 wherein extracting water from the film-forming composition includes extracting water vapor from the composition by heating the composition and applying a vacuum.
72. A method according to claim 38 wherein the dried portion of the film-forming composition has a water content of less than or equal to 25 percent by weight.
73. A method according to claim 38 wherein the formed film has a percent elongation of at least 50 percent at rupture at room temperature.
74. A method according to claim 38 wherein the film-forming composition has a viscosity of less than 100,000 cP as measured at a temperature less than 100 degrees C.
75. A method of producing a non-gelatin film, the method comprising:
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition comprising at least 40 percent water by weight;
(b) extracting a portion of the water from the film-forming composition to form a dried portion;
(c) forming the dried portion of the film-forming composition into a film without extracting a substantial additional portion of the water while forming the film, the formed film having a percent elongation of at least 50 percent at rupture at room temperature.
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition comprising at least 40 percent water by weight;
(b) extracting a portion of the water from the film-forming composition to form a dried portion;
(c) forming the dried portion of the film-forming composition into a film without extracting a substantial additional portion of the water while forming the film, the formed film having a percent elongation of at least 50 percent at rupture at room temperature.
76. A method according to claim 75 wherein combining includes mechanically mixing the hydrocolloid, the water, and the plasticizer.
77. A method according to claim 75 wherein combining includes heating the hydrocolloid, the water, and the plasticizer as they are combined.
78. A method according to claim 75, the method further comprising agitating and heating the film-forming composition as water is extracted.
79. A method according to claim 78 wherein the method further comprises agitating and heating the film-forming composition under pressure.
80. A method according to claim 75 wherein the film-forming composition further comprises a bulking agent.
81. A method according to claim 80 wherein the bulking agent comprises at least one starch ether or at least one esterified starch.
82. A method according to claim 75 wherein the at least one plasticizer is selected from the group consisting of sorbitol, maltitol, and glycerin.
83. A method according to claim 75 wherein the hydrocolloid is selected from the group consisting of carrageenan, alginates, agar, guar, pectin, locust bean gum, xanthan gum, starch, and gellan gum.
84. A method according to claim 75 wherein the hydrocolloid comprises carrageenan.
85. A method according to claim 84 wherein the carrageenan comprises iota carrageenan.
86. A method according to claim 85 wherein the iota carrageenan comprises 1-15 percent by weight of the film-forming composition.
87. A method according to claim 85 wherein the iota carrageenan comprises 3-8 percent by weight of the film-forming composition.
88. A method according to claim 84 wherein the carrageenan comprises kappa carrageenan.
89. A method according to claim 88 wherein the kappa carrageenan comprises 0.5-percent by weight of the film-forming composition.
90. A method according to claim 88 wherein the kappa carrageenan comprises 1-5 percent by weight of the film-forming composition.
91. A method according to claim 75 wherein the film-forming composition comprises:
(a) 3-9 weight percent carrageenan;
(b) 5-35 weight percent plasticizer; and (c) at least 40 weight percent water.
(a) 3-9 weight percent carrageenan;
(b) 5-35 weight percent plasticizer; and (c) at least 40 weight percent water.
92. A method according to claim 91 wherein the film-forming composition further comprises 10-40 weight percent bulking agent.
93. A method according to claim 92 wherein the bulking agent comprises starch.
94. A method according to claim 91 wherein the plasticizer comprises glycerin.
95. A method according to claim 91 wherein the plasticizer comprises sorbitol syrup.
96. A method according to claim 91 wherein the plasticizer comprises maltitol syrup.
97. A method according to claim 75 wherein the film-forming composition comprises:
(a) 4-10 weight percent carrageenan;
(b) 10-40 weight percent starch;
(c) 5-35 weight percent plasticizer; and (d) at least 40 weight percent water.
(a) 4-10 weight percent carrageenan;
(b) 10-40 weight percent starch;
(c) 5-35 weight percent plasticizer; and (d) at least 40 weight percent water.
98. A method according to claim 97 wherein the carrageenan comprises:
(a) 1-2 weight percent kappa carrageenan; and (b) 3-5 weight percent iota carrageenan.
(a) 1-2 weight percent kappa carrageenan; and (b) 3-5 weight percent iota carrageenan.
99. A method according to claim 75 wherein the dried portion of the film-forming composition comprises 8-25 percent water by weight.
100. A method according to claim 75 wherein the film-forming composition is preheated to 180-210 degrees Fahrenheit before water is extracted from the composition.
101. A method according to claim 75 wherein the film-forming composition has a viscosity less than 100,000 cP as measured at a temperature less than 100 degrees C.
102. A method according to claim 75 wherein the film-forming composition is heated under pressure to a temperature of at least 240 degrees as water is extracted from the composition.
103. A method according to claim 102 wherein the pressure is 1-29 inches Hg.
104. A method according to claim 102 wherein the film-forming composition is heated to a temperature of 240-280 degrees Fahrenheit as water is extracted from the composition.
105. A method according to claim 75 wherein extracting water from the film-forming composition includes passing the film-forming composition through an extruder/dryer.
106. A method according to claim 105 further comprising agitating the film-forming composition between cooperating rotating twin screws in the extruder/dryer as water is extracted.
107. A method according to claim 75 wherein forming the dried portion of the film-forming composition into a film includes extruding the dried portion through a film-forming die.
108. A method according to claim 75 wherein extracting water from the film-forming composition includes extracting water vapor from the composition by heating the composition and applying a vacuum.
109. A method according to claim 75 wherein the formed film has a tensile strength at rupture of at least 0.4 N/mm2 at room temperature.
110. A method according to claim 75 wherein the dried portion of the film-forming composition has a water content less than or equal to 25 percent by weight.
111. A method according to claim 75 wherein the film-forming composition has a viscosity of less than 100,000 cP as measured at a temperature less than 100 degrees C.
112. A method of producing a non-gelatin film, the method comprising:
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition having a viscosity of less than 100,000 cP as measured at a temperature less than 100 degrees C;
(b) extracting a portion of the water from the film-forming composition to form a dried portion having a water content less than or equal to 25 percent by weight; and (c) forming the dried portion of the film-forming composition into a film.
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition having a viscosity of less than 100,000 cP as measured at a temperature less than 100 degrees C;
(b) extracting a portion of the water from the film-forming composition to form a dried portion having a water content less than or equal to 25 percent by weight; and (c) forming the dried portion of the film-forming composition into a film.
113. A method according to claim 112 wherein combining includes mechanically mixing the hydrocolloid, the water, and the plasticizer.
114. A method according to claim 112 wherein combining includes heating the hydrocolloid, the water, and the plasticizer as they are combined.
115. A method according to claim 112, the method further comprising agitating and heating the film-forming composition as water is extracted.
116. A method according to claim 115 wherein the method further comprises agitating and heating the film-forming composition under pressure.
117. A method according to claim 112 wherein the film-forming composition further comprises a bulking agent.
118. A method according to claim 117 wherein the bulking agent comprises at least one starch ether or at least one esterified starch.
119. A method according to claim 112 wherein the at least one plasticizer is selected from the group consisting of sorbitol, maltitol, and glycerin.
120. A method according to claim 112 wherein the hydrocolloid is selected from the group consisting of carrageenan, alginates, agar, guar, pectin, locust bean gum, xanthan gum, starch, and gellan gum.
121. A method according to claim 112 wherein the hydrocolloid comprises carrageenan.
122. A method according to claim 121 wherein the carrageenan comprises iota carrageenan.
123. A method according to claim 122 wherein the iota carrageenan comprises 1-percent by weight of the film-forming composition.
124. A method according to claim 122 wherein the iota carrageenan comprises 3-8 percent by weight of the film-forming composition.
125. A method according to claim 121 wherein the carrageenan comprises kappa carrageenan.
126. A method according to claim 125 wherein the kappa carrageenan comprises 0.5-8 percent by weight of the film-forming composition.
127. A method according to claim 125 wherein the kappa carrageenan comprises 1-percent by weight of the film-forming composition.
128. A method according to claim 112 wherein the film-forming composition comprises:
(a) 3-9 weight percent carrageenan;
(b) 5-35 weight percent plasticizer; and (c) at least 40 weight percent water.
(a) 3-9 weight percent carrageenan;
(b) 5-35 weight percent plasticizer; and (c) at least 40 weight percent water.
129. A method according to claim 128 wherein the film-forming composition further comprises 10-40 weight percent bulking agent.
130. A method according to claim 129 wherein the bulking agent comprises starch.
131. A method according to claim 128 wherein the plasticizer comprises glycerin.
132. A method according to claim 128 wherein the plasticizer comprises sorbitol syrup.
133. A method according to claim 128 wherein plasticizer comprises maltitol syrup.
134. A method according to claim 112 wherein the film-forming composition comprises:
(a) 4-10 weight percent carrageenan;
(b) 10-40 weight percent starch;
(c) 5-35 weight percent plasticizer; and (d) at least 40 weight percent water.
(a) 4-10 weight percent carrageenan;
(b) 10-40 weight percent starch;
(c) 5-35 weight percent plasticizer; and (d) at least 40 weight percent water.
135. A method according to claim 134 wherein the carrageenan comprises:
(a) 1-2 weight percent kappa carrageenan; and (b) 3-5 weight percent iota carrageenan.
(a) 1-2 weight percent kappa carrageenan; and (b) 3-5 weight percent iota carrageenan.
136. A method according to claim 112 wherein the dried portion of the film-forming composition comprises 8-25 percent water by weight.
137. A method according to claim 112 wherein the film-forming composition is preheated to 180-210 degrees Fahrenheit before water is extracted from the composition.
138. A method according to claim 112 wherein the film-forming composition has a viscosity less than 100,000 cP as measured at a temperature less than 100 degrees C.
139. A method according to claim 112 wherein the film-forming composition is heated under pressure to a temperature of at least 240 degrees as water is extracted from the composition.
140. A method according to claim 139 wherein the pressure is 1-29 inches Hg.
141. A method according to claim 139 wherein the film-forming composition is heated to a temperature of 240-280 degrees Fahrenheit as water is extracted from the composition.
142. A method according to claim 112 wherein extracting water from the film-forming composition includes passing the film-forming composition through an extruder/dryer.
143. A method according to claim 142 further comprising agitating the film-forming composition between cooperating rotating twin screws in the extruder/dryer as water is extracted.
144. A method according to claim 112 wherein forming the dried portion of the film-forming composition into a film includes extruding the dried portion through a film-forming die.
145. A method according to claim 112 wherein extracting water from the film-forming composition includes extracting water vapor from the composition by heating the composition and applying a vacuum.
146. A method according to claim 112 wherein the formed film has a tensile strength at rupture of at least 0.4 N/mm2 at room temperature.
147. A method according to claim 112 wherein the formed film has a percent elongation of at least 50 percent at rupture at room temperature.
148. A method of producing a non-gelatin film, the method comprising:
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition having a viscosity of less than 100,000 cP as measured at a temperature less than 100 degrees C;
(b) extracting a portion of the water from the film-forming composition to form a dried portion; and (c) forming the dried portion of the film-forming composition into a film, without extracting a substantial additional portion of the water while forming the film, wherein the formed film has a tensile strength at rupture of at least 0.4 N/mm2 at room temperature.
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition having a viscosity of less than 100,000 cP as measured at a temperature less than 100 degrees C;
(b) extracting a portion of the water from the film-forming composition to form a dried portion; and (c) forming the dried portion of the film-forming composition into a film, without extracting a substantial additional portion of the water while forming the film, wherein the formed film has a tensile strength at rupture of at least 0.4 N/mm2 at room temperature.
149. A method according to claim 148 wherein combining includes mechanically mixing the hydrocolloid, the water, and the plasticizer.
150. A method according to claim 148 wherein combining includes heating the hydrocolloid, the water, and the plasticizer as they are combined.
151. A method according to claim 148, the method further comprising agitating and heating the film-forming composition as water is extracted.
152. A method according to claim 148 wherein the method further comprises agitating and heating the film-forming composition under pressure.
153. A method according to claim 148 wherein the film-forming composition further comprises a bulking agent.
154. A method according to claim 153 wherein the bulking agent comprises at least one starch ether or at least one esterified starch.
155. A method according to claim 148 wherein the at least one plasticizer is selected from the group consisting of sorbitol, maltitol, and glycerin.
156. A method according to claim 148 wherein the hydrocolloid is selected from the group consisting of carrageenan, alginates, agar, guar, pectin, locust bean gum, xanthan gum, starch, and gellan gum.
157. A method according to claim 148 wherein the hydrocolloid comprises carrageenan.
158. A method according to claim 157 wherein the carrageenan comprises iota carrageenan.
159. A method according to claim 158 wherein the iota carrageenan comprises 1-percent by weight of the film-forming composition.
160. A method according to claim 158 wherein the iota carrageenan comprises 3-8 percent by weight of the film-forming composition.
161. A method according to claim 157 wherein the carrageenan comprises kappa carrageenan.
162. A method according to claim 161 wherein the kappa carrageenan comprises 0.5-8 percent by weight of the film-forming composition.
163. A method according to claim 161 wherein the kappa carrageenan comprises 1-percent by weight of the film-forming composition.
164. A method according to claim 148 wherein the film-forming composition comprises:
(a) 3-9 weight percent carrageenan;
(b) 5-35 weight percent plasticizer; and (c) at least 40 weight percent water.
(a) 3-9 weight percent carrageenan;
(b) 5-35 weight percent plasticizer; and (c) at least 40 weight percent water.
165. A method according to claim 164 wherein the film-forming composition further comprises 10-40 weight percent bulking agent.
166. A method according to claim 165 wherein the bulking agent comprises starch.
167. A method according to claim 164 wherein the film-forming composition further comprises glycerin.
168. A method according to claim 164 wherein the plasticizer comprises sorbitol syrup.
169. A method according to claim 164 wherein the plasticizer comprises maltitol syrup.
170. A method according to claim 148 wherein the film-forming composition comprises:
(a) 4-10 weight percent carrageenan;
(b) 10-40 weight percent starch;
(c) 5-35 weight percent plasticizer; and (d) at least 40 weight percent water.
(a) 4-10 weight percent carrageenan;
(b) 10-40 weight percent starch;
(c) 5-35 weight percent plasticizer; and (d) at least 40 weight percent water.
171. A method according to claim 170 wherein the carrageenan comprises:
(a) 1-2 weight percent kappa carrageenan; and (b) 3-5 weight percent iota carrageenan.
(a) 1-2 weight percent kappa carrageenan; and (b) 3-5 weight percent iota carrageenan.
172. A method according to claim 148 wherein the dried portion of the film-forming composition comprises 8-25 percent water by weight.
173. A method according to claim 148 wherein the film-forming composition is preheated to 180-210 degrees Fahrenheit before water is extracted from the composition.
174. A method according to claim 148 wherein the film-forming composition has a viscosity less than 100,000 cP as measured at a temperature less than 100 degrees C.
175. A method according to claim 148 wherein the film-forming composition is heated under pressure to a temperature of at least 240 degrees as water is extracted from the composition.
176. A method according to claim 175 wherein the pressure is 1-29 inches Hg.
177. A method according to claim 175 wherein the film-forming composition is heated to a temperature of 240-280 degrees Fahrenheit as water is extracted from the composition.
178. A method according to claim 148 wherein extracting water from the film-forming composition includes passing the film-forming composition through an extruder/dryer.
179. A method according to claim 178 further comprising agitating the film-forming composition between cooperating rotating twin screws in the extruder/dryer as water is extracted.
180. A method according to claim 148 wherein forming the dried portion of the film-forming composition into a film includes extruding the dried portion through a film-forming die.
181. A method according to claim 148 wherein extracting water from the film-forming composition includes extracting water vapor from the composition by heating the composition and applying a vacuum.
182. A method according to claim 148 wherein the film-forming material has a water content of at least 40 percent by weight.
183. A method according to claim 148 wherein the formed film has a percent elongation of at least 50 percent at rupture at room temperature.
184. A method according to claim 148 wherein the dried portion of the film-forming composition has a water content of less than or equal to 25 percent by weight.
185. A method of producing a non-gelatin film, the method comprising:
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition having a viscosity of less than 100,000 cP as measured at a temperature less than 100 degrees C;
(b) extracting a portion of the water from the film-forming composition to form a dried portion; and (c) forming the dried portion of the film-forming composition into a film without extracting a substantial additional portion of the water while forming the film, the formed film having a percent elongation of at least 50 percent at rupture at room temperature.
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition having a viscosity of less than 100,000 cP as measured at a temperature less than 100 degrees C;
(b) extracting a portion of the water from the film-forming composition to form a dried portion; and (c) forming the dried portion of the film-forming composition into a film without extracting a substantial additional portion of the water while forming the film, the formed film having a percent elongation of at least 50 percent at rupture at room temperature.
186. A method according to claim 185 wherein combining includes mechanically mixing the hydrocolloid, the water, and the plasticizer.
187. A method according to claim 185 wherein combining includes heating the hydrocolloid, the water, and the plasticizer as they are combined.
188. A method according to claim 185, the method further comprising agitating and heating the film-forming composition as water is extracted.
189. A method according to claim 188 wherein the method further comprises agitating and heating the film-forming composition under pressure.
190. A method according to claim 185 wherein the film-forming composition further comprises a bulking agent.
191. A method according to claim 190 wherein the bulking agent comprises at least one starch ether or at least one esterified starch.
192. A method according to claim 185 wherein the at least one plasticizer is selected from the group consisting of sorbitol, maltitol, and glycerin.
193. A method according to claim 185 wherein the hydrocolloid is selected from the group consisting of carrageenan, alginates, agar, guar, pectin, locust bean gum, xanthan gum, starch, and gellan gum.
194. A method according to claim 185 wherein the hydrocolloid comprises carrageenan.
195. A method according to claim 194 wherein the carrageenan comprises iota carrageenan.
196. A method according to claim 195 wherein the iota carrageenan comprises 1-percent by weight of the film-forming composition.
197. A method according to claim 195 wherein the iota carrageenan comprises 3-8 percent by weight of the film-forming composition.
198. A method according to claim 194 wherein the carrageenan comprises kappa carrageenan.
199. A method according to claim 198 wherein the kappa carrageenan comprises 0.5-8 percent by weight of the film-forming composition.
200. A method according to claim 198 wherein the kappa carrageenan comprises 1-percent by weight of the film-forming composition.
201. A method according to claim 185 wherein the film-forming composition comprises:
(a) 3-9 weight percent carrageenan;
(b) 5-35 weight percent plasticizer; and (c) at least 40 weight percent water.
(a) 3-9 weight percent carrageenan;
(b) 5-35 weight percent plasticizer; and (c) at least 40 weight percent water.
202. A method according to claim 201 wherein the film-forming composition further comprises 10-40 weight percent bulking agent.
203. A method according to claim 202 wherein the bulking agent comprises starch.
204. A method according to claim 201 wherein the plasticizer comprises glycerin.
205. A method according to claim 196 wherein the plasticizer comprises sorbitol syrup.
206. A method according to claim 196 wherein the plasticizer comprises maltitol syrup.
207. A method according to claim 185 wherein the film-forming composition comprises:
(a) 4-10 weight percent carrageenan;
(b) 10-40 weight percent starch;
(c) 5-35 weight percent plasticizer; and (d) at least 40 weight percent water.
(a) 4-10 weight percent carrageenan;
(b) 10-40 weight percent starch;
(c) 5-35 weight percent plasticizer; and (d) at least 40 weight percent water.
208. A method according to claim 201 wherein the carrageenan comprises:
(a) 1-2 weight percent kappa carrageenan; and (b) 3-5 weight percent iota carrageenan.
(a) 1-2 weight percent kappa carrageenan; and (b) 3-5 weight percent iota carrageenan.
209. A method according to claim 185 wherein the dried portion of the film-forming composition comprises 8-25 percent water by weight.
210. A method according to claim 185 wherein the film-forming composition is preheated to 180-210 degrees Fahrenheit before water is extracted from the composition.
211. A method according to claim 185 wherein the film-forming composition has a viscosity less than 100,000 cP as measured at a temperature less than 100 degrees C.
212. A method according to claim 185 wherein the film-forming composition is heated under pressure to a temperature of at least 240 degrees as water is extracted from the composition.
213. A method according to claim 212 wherein the pressure is 1-29 inches Hg.
214. A method according to claim 212 wherein the film-forming composition is heated to a temperature of 240-280 degrees Fahrenheit as water is extracted from the composition.
215. A method according to claim 185 wherein extracting water from the film-forming composition includes passing the film-forming composition through an extruder/dryer.
216. A method according to claim 215 further comprising agitating the film-forming composition between cooperating rotating twin screws in the extruder/dryer as water is extracted.
217. A method according to claim 185 wherein forming the dried portion of the film-forming composition into a film includes extruding the dried portion through a film-forming die.
218. A method according to claim 185 wherein extracting water from the film-forming composition includes extracting water vapor from the composition by heating the composition and applying a vacuum.
219. A method according to claim 185 wherein the formed film has a tensile strength at rupture of at least 0.4 N/mm2 at room temperature.
220. A method according to claim 185 wherein the film-forming composition comprises at least 40 percent water by weight.
221. A method according to claim 185 wherein the dried portion of the film-forming composition has a water content less than or equal to 25 percent by weight.
222. A method of producing a non-gelatin film, the method comprising:
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition comprising at least 40 percent water by weight;
(b) extracting a portion of the water from the film-forming composition to form a dried portion having a water content of less than or equal to 25 percent by weight; and (c) forming the dried portion of the film-forming composition into a film without extracting a substantial additional portion of the water while forming the film.
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition comprising at least 40 percent water by weight;
(b) extracting a portion of the water from the film-forming composition to form a dried portion having a water content of less than or equal to 25 percent by weight; and (c) forming the dried portion of the film-forming composition into a film without extracting a substantial additional portion of the water while forming the film.
223. A method of producing a non-gelatin film, the method comprising:
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition having a viscosity of less than 100,000 cP as measured at a temperature less than 100 degrees C;
(b) extracting a portion of the water from the film-forming composition to form a dried portion having a water content less than or equal to 25 percent by weight; and (c) forming the dried portion of the film-forming composition into a film without extracting a substantial additional portion of the water while forming the film.
(a) combining at least one non-gelatin hydrocolloid, water, and at least one plasticizer into a substantially homogeneous film-forming composition having a viscosity of less than 100,000 cP as measured at a temperature less than 100 degrees C;
(b) extracting a portion of the water from the film-forming composition to form a dried portion having a water content less than or equal to 25 percent by weight; and (c) forming the dried portion of the film-forming composition into a film without extracting a substantial additional portion of the water while forming the film.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/610,306 US7887838B2 (en) | 2002-01-18 | 2003-06-30 | Non-gelatin film and method and apparatus for producing same |
| US10/610,306 | 2003-06-30 | ||
| PCT/US2004/020187 WO2005004840A2 (en) | 2003-06-30 | 2004-06-23 | Non-gelatin film and method and apparatus for producing same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2530619A1 CA2530619A1 (en) | 2005-01-20 |
| CA2530619C true CA2530619C (en) | 2011-12-20 |
Family
ID=34062316
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2530619A Expired - Fee Related CA2530619C (en) | 2003-06-30 | 2004-06-23 | Non-gelatin film and method and apparatus for producing same |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US7887838B2 (en) |
| EP (1) | EP1648424A2 (en) |
| JP (1) | JP2007524527A (en) |
| CA (1) | CA2530619C (en) |
| WO (1) | WO2005004840A2 (en) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4414670B2 (en) * | 2003-04-10 | 2010-02-10 | 松谷化学工業株式会社 | Process for producing glucose polymer having ion exchange ability and composition containing the same |
| US7816341B2 (en) | 2003-04-14 | 2010-10-19 | Fmc Corporation | Homogeneous, thermoreversible gel containing reduced viscosity carrageenan and products made therefrom |
| US20050013847A1 (en) * | 2003-04-14 | 2005-01-20 | Fmc Corporation | Delivery systems of homogeneous, thermoreversible alginate films |
| WO2004091539A2 (en) * | 2003-04-14 | 2004-10-28 | Fmc Corporation | Fluid mixing methods and apparatus |
| US8627828B2 (en) * | 2003-11-07 | 2014-01-14 | U.S. Smokeless Tobacco Company Llc | Tobacco compositions |
| EP1691631A4 (en) * | 2003-11-07 | 2012-09-05 | Us Smokeless Tobacco Co | Tobacco compositions |
| US7494667B2 (en) * | 2004-03-02 | 2009-02-24 | Brunob Ii B.V. | Blends of different acyl gellan gums and starch |
| US20050196437A1 (en) * | 2004-03-02 | 2005-09-08 | Bednarz Christina A. | Hard capsules |
| US8231896B2 (en) | 2004-11-08 | 2012-07-31 | R.P. Scherer Technologies, Llc | Non-gelatin soft capsule system |
| US8497258B2 (en) | 2005-11-12 | 2013-07-30 | The Regents Of The University Of California | Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract |
| CA2572937A1 (en) * | 2005-12-27 | 2007-06-27 | Christopher Black | Paintball and method of manufacture |
| US20090260536A1 (en) * | 2006-12-19 | 2009-10-22 | Procaps L.P. | Paintball and method of manufacture |
| JP5539621B2 (en) * | 2008-01-28 | 2014-07-02 | 三生医薬株式会社 | Capsule skin composition and capsule |
| KR101361952B1 (en) * | 2008-09-26 | 2014-02-11 | 가부시키가이샤 산쿄 | Process for producing soft capsule and apparatus for producing the same |
| WO2010144865A2 (en) | 2009-06-12 | 2010-12-16 | Meritage Pharma, Inc. | Methods for treating gastrointestinal disorders |
| JP5696149B2 (en) * | 2009-09-10 | 2015-04-08 | エフ エム シー コーポレーションＦｍｃ Ｃｏｒｐｏｒａｔｉｏｎ | Seamless alginate capsules |
| JP5597770B2 (en) * | 2011-04-20 | 2014-10-01 | サフン カプセル カンパニー， リミテッド | Non-animal soft capsule coating composition with improved disintegration and coating hardness |
| KR102616316B1 (en) * | 2011-09-12 | 2023-12-20 | 제임스 비. 울프 | improved formed food product |
| US20130062371A1 (en) * | 2011-09-12 | 2013-03-14 | James B. Wolff | System and method for creating a venturi effect within an orifice |
| US20130164425A1 (en) * | 2011-09-12 | 2013-06-27 | James B. Wolff | System and method for creating a venturi effect within an orifice |
| CA2869882C (en) * | 2012-04-20 | 2019-09-10 | Eisai R&D Management Co., Ltd. | Capsule formulation |
| EP2968081A4 (en) | 2013-03-15 | 2016-08-10 | Banner Life Sciences Llc | Non-gelatin enteric soft capsules |
| JP5769760B2 (en) * | 2013-06-25 | 2015-08-26 | アール．ピー． シェーラー テクノロジーズ エルエルシー | Shell forming composition for soft capsule and soft capsule |
| WO2015157150A1 (en) | 2014-04-07 | 2015-10-15 | Banner Life Sciences Llc | Opioid abuse-deterrent controlled release formulations |
| US10772842B2 (en) | 2015-01-09 | 2020-09-15 | Patheon Softgels Inc. | Abuse-deterrent opioids |
| MX2017007420A (en) | 2014-12-18 | 2017-11-06 | Colgate Palmolive Co | Oral care compositions having high water content and micro robustness. |
| JP5977470B1 (en) | 2015-08-05 | 2016-08-24 | 富士カプセル株式会社 | Composition for soft capsule film |
| CN110075081A (en) * | 2019-06-12 | 2019-08-02 | 江苏艾兰得营养品有限公司 | A kind of soft capsule and preparation method thereof and purposes |
| WO2021072092A1 (en) * | 2019-10-09 | 2021-04-15 | R.P. Scherer Technologies, Llc | Non-animal softgel capsule formulations, methods of preparation, and methods of use thereof |
| WO2023031915A1 (en) | 2021-08-30 | 2023-03-09 | Redefine Meat Ltd. | An edible hydrogel, method of production and uses thereof |
| WO2024064875A1 (en) * | 2022-09-23 | 2024-03-28 | Cargill, Incorporated | Natural based carbomer replacement |
| CN117379388A (en) * | 2023-11-01 | 2024-01-12 | 秦皇岛稷中食品有限公司 | Preparation method and application of low-gel-point low-melting-point thermal reversible gelling composition |
Family Cites Families (96)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL113450C (en) | 1953-06-10 | |||
| US2802000A (en) | 1953-08-13 | 1957-08-06 | Nat Starch Products Inc | Ungelatinized cold water soluble starch ethers |
| US2825727A (en) | 1954-05-19 | 1958-03-04 | Nat Starch Products Inc | Ungelatinized starch products of improved properties and method of making the same |
| NL122082C (en) | 1959-12-01 | |||
| US3058827A (en) | 1960-02-09 | 1962-10-16 | Eastman Kodak Co | Dialdehyde starch as gelatin hardener |
| US3499962A (en) | 1967-08-24 | 1970-03-10 | Nat Starch Chem Corp | Encapsulation of water insoluble materials |
| US3607394A (en) | 1969-05-29 | 1971-09-21 | Felix Joseph Germino | Novel pregelatinized starches and process for preparing same |
| US3865603A (en) | 1972-07-17 | 1975-02-11 | Nat Starch Chem Corp | Modified starch-extended gelatin compositions |
| JPS50105766A (en) | 1974-01-29 | 1975-08-20 | ||
| JPS5717692B2 (en) | 1974-01-29 | 1982-04-12 | ||
| US4009291A (en) | 1974-03-25 | 1977-02-22 | General Foods Corporation | Cold water soluble stable bulked starch |
| US3956173A (en) | 1974-07-05 | 1976-05-11 | Hercules Incorporated | Preparation of gels based on carrageenan |
| CA1045936A (en) | 1975-03-24 | 1979-01-09 | Frederick W. Comer | Clear, elastic, water gels based on carrageenan |
| US4129134A (en) | 1975-04-14 | 1978-12-12 | Philip Morris Incorporated | Smoking article |
| US4026986A (en) | 1975-05-22 | 1977-05-31 | The Dow Chemical Company | Capsule shell |
| US4231803A (en) | 1978-05-22 | 1980-11-04 | Anheuser-Busch Incorporated | Starch adhesive composition containing an oxidized waxy starch ester |
| US4276320A (en) | 1980-01-25 | 1981-06-30 | Fmc Corporation | Compositions and method for preparing dessert gels |
| FR2508051B1 (en) | 1981-06-23 | 1986-12-05 | Roquette Freres | COMPOSITION AND METHOD FOR FORMING A TEMPORARY PROTECTIVE COATING AND OBJECT THUS PROTECTED |
| FR2540153B1 (en) | 1982-10-12 | 1987-02-13 | Roquette Freres | COMPOSITION AND METHOD FOR COATING PAPER AND CARDBOARD, PROCESS FOR PREPARING THE COMPOSITION AND PAPER AND CARDBOARD THUS OBTAINED |
| US4643894A (en) | 1984-07-24 | 1987-02-17 | Colorcon, Inc. | Maltodextrin coating |
| US4615897A (en) | 1985-02-25 | 1986-10-07 | Nabisco Brands, Inc. | Cold water soluble gelatin |
| FR2593510B1 (en) * | 1985-07-31 | 1989-07-13 | Werner & Pfleiderer | PROCESS FOR THE PREPARATION OF HIGH VISCOSITY POLYHEXAMETHYLENEADIPAMIDE |
| DE3529694A1 (en) | 1985-08-20 | 1987-02-26 | Scherer Gmbh R P | GELATINE CAPSULES AND METHOD FOR THEIR PRODUCTION |
| US4795642A (en) | 1986-05-01 | 1989-01-03 | Pharmacaps, Inc. | Gelatin-encapsulated controlled-release composition |
| JPS63118229A (en) | 1986-11-07 | 1988-05-23 | Idemitsu Petrochem Co Ltd | Preparation of thermoplastic resin sheets |
| GB8628068D0 (en) | 1986-11-24 | 1986-12-31 | Unilever Plc | Aqueous gel comprising carrageenan |
| CN1036967A (en) | 1988-02-04 | 1989-11-08 | 武田药品工业株式会社 | Edible film |
| US4935243A (en) | 1988-12-19 | 1990-06-19 | Pharmacaps, Inc. | Chewable, edible soft gelatin capsule |
| US5089307A (en) | 1989-05-23 | 1992-02-18 | Mitsubishi Rayon Co., Ltd. | Edible film and method of making same |
| NO306471B1 (en) | 1989-07-11 | 1999-11-08 | Warner Lambert Co | Polymer blend comprising structure-modified starch, as well as the use of the blend |
| HU208985B (en) | 1989-07-18 | 1994-02-28 | Warner Lambert Co | Polymere-based mixture composition containing destructurated starch |
| HU211427B (en) | 1989-07-18 | 1995-11-28 | Warner Lambert Co | Composition containing destructurized starch and thermoplastic destructurized-starch solid product having substantial dimensional stability |
| CA2021119C (en) | 1989-07-20 | 2004-05-18 | Jean-Pierre Sachetto | Polymer base blend compositions containing destructurized starch |
| US5146730A (en) | 1989-09-20 | 1992-09-15 | Banner Gelatin Products Corp. | Film-enrobed unitary-core medicament and the like |
| JPH03121825A (en) | 1989-10-05 | 1991-05-23 | Unitika Ltd | Manufacture of low temperature heat-sealing polyester film |
| JPH03127945A (en) | 1989-10-12 | 1991-05-31 | Japan Steel Works Ltd:The | Production of tissual film food and apparatus therefor |
| JPH03190709A (en) | 1989-12-21 | 1991-08-20 | Diafoil Co Ltd | Extrusion molding of thermoplastic resin |
| JP3121825B2 (en) | 1990-04-27 | 2001-01-09 | 日産自動車株式会社 | Holographic display device |
| JPH0489841A (en) | 1990-08-03 | 1992-03-24 | Mitsubishi Rayon Co Ltd | Tubular polysaccharide film and its production |
| GB9017800D0 (en) | 1990-08-14 | 1990-09-26 | Unilever Plc | Moisture barrier and its preparation |
| DE69127456T2 (en) | 1990-11-28 | 1998-01-02 | Scherer Corp R P | GELATIN CAPSULES SUBSTITUTED BY STRENGTH WITH A HIGH AMYLOSE CONTENT |
| JP3190709B2 (en) | 1991-10-15 | 2001-07-23 | ソニー株式会社 | Electronics |
| EP0547551B1 (en) | 1991-12-16 | 1997-11-05 | National Starch and Chemical Investment Holding Corporation | Edible films |
| AU673355B2 (en) | 1992-03-31 | 1996-11-07 | National Starch And Chemical Investment Holding Corporation | Esterified starch composition |
| US5334640A (en) | 1992-04-08 | 1994-08-02 | Clover Consolidated, Ltd. | Ionically covalently crosslinked and crosslinkable biocompatible encapsulation compositions and methods |
| NZ244796A (en) | 1992-08-18 | 1995-05-26 | Scherer Corp R P | Capsule shell of soft gelatin contains a medicament and has a removable tab |
| US5451673A (en) | 1993-04-23 | 1995-09-19 | The United States Of America As Represented By The Secretary Of Agriculture | Films fabricated from mixtures of pectin and starch |
| US5342626A (en) | 1993-04-27 | 1994-08-30 | Merck & Co., Inc. | Composition and process for gelatin-free soft capsules |
| GB9313329D0 (en) | 1993-06-28 | 1993-08-11 | Scherer Ltd R P | Softgel capsule shell compositions |
| JP3127945B2 (en) | 1993-07-30 | 2001-01-29 | 財団法人小林理学研究所 | Moving sound source identification method and apparatus |
| JP3325091B2 (en) | 1993-08-31 | 2002-09-17 | 株式会社トクヤマ | Method for producing porous film |
| ATE162071T1 (en) * | 1993-10-01 | 1998-01-15 | Scherer Corp R P | COMPOSITIONS FOR DISTRIBUTING FRAGRANCE |
| JPH07196478A (en) | 1993-12-30 | 1995-08-01 | Hajime Sugii | Soft capsule for highly safe food and medicine |
| US5393054A (en) | 1994-03-09 | 1995-02-28 | Zap Paintball Corporation | Paint ball |
| US5756123A (en) | 1994-12-01 | 1998-05-26 | Japan Elanco Co., Ltd. | Capsule shell |
| GB2298560B (en) | 1994-12-23 | 1998-07-08 | Cpc International Inc | Low-fat cake donuts and process therefor |
| US5656294A (en) | 1995-06-07 | 1997-08-12 | Cibus Pharmaceutical, Inc. | Colonic delivery of drugs |
| US5811388A (en) | 1995-06-07 | 1998-09-22 | Cibus Pharmaceutical, Inc. | Delivery of drugs to the lower GI tract |
| US5672699A (en) | 1995-09-06 | 1997-09-30 | National Starch And Chemical Investment Holding Corporation | Process for preparation of hydrophobic starch derivatives |
| US5932639A (en) | 1996-05-06 | 1999-08-03 | National Starch And Chemical Investment Holding Corporation | Maltodextrin-based adhesives |
| FI108038B (en) | 1996-06-25 | 2001-11-15 | Polymer Corex Kuopio Ltd Oy | Hydrophobic polymer dispersion and process for its preparation |
| US5726008A (en) | 1996-09-18 | 1998-03-10 | Eastman Kodak Company | Photographic elements with improved vehicles |
| FR2757173A1 (en) * | 1996-12-17 | 1998-06-19 | Warner Lambert Co | POLYMERIC COMPOSITIONS OF NON-ANIMAL ORIGIN FOR FILM FORMATION |
| US5976586A (en) | 1997-03-10 | 1999-11-02 | Lawrence Foods | Glaze composition with vegetable gums |
| US6030641A (en) | 1997-06-03 | 2000-02-29 | Uni Colloid Kabushiki Kaisha | Sustained release capsule and method for preparing the same |
| FR2767070B1 (en) * | 1997-08-08 | 1999-09-17 | Laurence Paris | AQUEOUS VISCOUS COMPOSITION, LIMPID OR NOT, FOR THE MANUFACTURE OF SOFT CAPSULES AND HARD CAPSULES, AND METHOD FOR MANUFACTURING FILMS FOR SUCH CAPSULES |
| NL1009107C2 (en) | 1997-11-12 | 1999-06-15 | Banner Pharmacaps Inc | Extrusion device for forming multi layer gelatine films used to form soft gel capsules - contains two height adjustable gate valves covering nozzle opening to control thickness of the individual extruded gelatine film layers |
| US6007614A (en) | 1997-12-30 | 1999-12-28 | National Starch And Chemical Investment Holding Corporation | Starch esters as moisture vapor barrier coatings |
| GB9802201D0 (en) * | 1998-02-03 | 1998-04-01 | Cerestar Holding Bv | Free-flowable directly compressible starch as binder,disintegrant and filler for compresion tablets and hard gelatine capsules |
| US5962053A (en) * | 1998-02-17 | 1999-10-05 | Viskase Corporation | Edible film and method |
| JP4089841B2 (en) | 1998-03-12 | 2008-05-28 | 株式会社Ａｄｅｋａ | Detergent containing a surfactant comprising a readily soluble acylated polylysine |
| US6146570A (en) | 1998-03-20 | 2000-11-14 | Rhodia Inc. | Process for producing extruded hydrocolloid granules |
| US6063915A (en) | 1998-07-30 | 2000-05-16 | Hercules Incorporated | Carrageenan compositions and methods for their production |
| US6214376B1 (en) | 1998-08-25 | 2001-04-10 | Banner Pharmacaps, Inc. | Non-gelatin substitutes for oral delivery capsules, their composition and process of manufacture |
| JP2000127225A (en) | 1998-10-28 | 2000-05-09 | Toshiba Mach Co Ltd | Method and apparatus for controlling operation of twin- screw extruder |
| US6210709B1 (en) | 1999-03-24 | 2001-04-03 | Elementis Specialties, Inc. | Flexible gelatin free encapsulation material useful for pharmaceuticals, paint balls and other formulations |
| DE19914742A1 (en) | 1999-03-31 | 2000-10-12 | Siemens Ag | Method of transferring data |
| US6340473B1 (en) * | 1999-07-07 | 2002-01-22 | R.P. Scherer Technologies, Inc. | Film forming compositions comprising modified starches and iota-carrageenan and methods for manufacturing soft capsules using same |
| EP1103254B1 (en) | 1999-11-19 | 2005-03-23 | Swiss Caps Rechte und Lizenzen AG | Process to manufacture starch-containing shaped bodies,mass containing homogenized starch and device to manufacture soft capsules |
| US6528088B1 (en) * | 2000-06-01 | 2003-03-04 | A. E. Staley Manufacturing Co. | Highly flexible starch-based films |
| US6375981B1 (en) * | 2000-06-01 | 2002-04-23 | A. E. Staley Manufacturing Co. | Modified starch as a replacement for gelatin in soft gel films and capsules |
| US6607748B1 (en) * | 2000-06-29 | 2003-08-19 | Vincent Lenaerts | Cross-linked high amylose starch for use in controlled-release pharmaceutical formulations and processes for its manufacture |
| EP1216680B1 (en) * | 2000-12-20 | 2006-03-15 | Swiss Caps Rechte und Lizenzen AG | Rotary die process and filling wedge for manufacturing capsules, in particular soft capsules |
| US20020155200A1 (en) * | 2000-12-22 | 2002-10-24 | Reg Macquarrie | Edible film formulation |
| EP1249219B1 (en) * | 2000-12-29 | 2009-10-21 | Swiss Caps Rechte und Lizenzen AG | Method and apparatus for manufacturing shaped bodies made of a biopolymer material |
| GB2375340B (en) * | 2001-05-10 | 2003-09-10 | Croda Int Plc | Gelatin substitute |
| EP1258242A1 (en) | 2001-05-15 | 2002-11-20 | Swiss Caps Rechte und Lizenzen AG | Process of manufacturing shaped bodies, in particular soft capsules |
| US6884060B2 (en) * | 2001-11-02 | 2005-04-26 | R.P. Scherer Technologies, Inc. | Apparatus for manufacturing encapsulated products |
| US6745546B2 (en) * | 2001-11-02 | 2004-06-08 | R.P. Scherer Technologies, Inc. | Encapsulation machine with valved injection wedge |
| US6949256B2 (en) * | 2002-01-18 | 2005-09-27 | Banner Pharmacaps, Inc. | Non-gelatin capsule shell formulation |
| US20050008677A1 (en) * | 2003-04-14 | 2005-01-13 | Fmc Corporation | Delivery system of homogeneous, thermoreversible gel film containing kappa-2 carrageenan |
| US20050019295A1 (en) * | 2003-04-14 | 2005-01-27 | Fmc Corporation | Homogeneous, thermoreversible low viscosity polymannan gum films and soft capsules made therefrom |
| US20050019294A1 (en) * | 2003-04-14 | 2005-01-27 | Fmc Corporation | Homogeneous, thermoreversible alginate films and soft capsules made therefrom |
| WO2004091539A2 (en) * | 2003-04-14 | 2004-10-28 | Fmc Corporation | Fluid mixing methods and apparatus |
| US20050013847A1 (en) * | 2003-04-14 | 2005-01-20 | Fmc Corporation | Delivery systems of homogeneous, thermoreversible alginate films |
| US7816341B2 (en) * | 2003-04-14 | 2010-10-19 | Fmc Corporation | Homogeneous, thermoreversible gel containing reduced viscosity carrageenan and products made therefrom |
-
2003
- 2003-06-30 US US10/610,306 patent/US7887838B2/en not_active Expired - Fee Related
-
2004
- 2004-06-23 CA CA2530619A patent/CA2530619C/en not_active Expired - Fee Related
- 2004-06-23 EP EP04755975A patent/EP1648424A2/en not_active Withdrawn
- 2004-06-23 WO PCT/US2004/020187 patent/WO2005004840A2/en active Application Filing
- 2004-06-23 JP JP2006517591A patent/JP2007524527A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CA2530619A1 (en) | 2005-01-20 |
| WO2005004840A2 (en) | 2005-01-20 |
| US7887838B2 (en) | 2011-02-15 |
| JP2007524527A (en) | 2007-08-30 |
| WO2005004840A3 (en) | 2005-06-30 |
| EP1648424A2 (en) | 2006-04-26 |
| US20040052839A1 (en) | 2004-03-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2530619C (en) | Non-gelatin film and method and apparatus for producing same | |
| CA2473312C (en) | Non-gelatin capsule shell formulation comprising iota-carrageenan and kappa-carrageenan | |
| AU2003237365A1 (en) | Non-gelatin capsule shell formulation comprising iota-carrageenan and kappa-carrageenan | |
| CA2522295C (en) | Homogeneous, thermoreversible gel film containing kappa-2 carrageenan and soft capsules made therefrom | |
| JP4252619B1 (en) | Method for producing enteric soft capsule and enteric soft capsule | |
| CA2559735A1 (en) | Biopolymer compositions and products thereof | |
| KR20100014618A (en) | Non-animal derived soft capsule shell and soft capsule having the same | |
| US20050014852A1 (en) | Homogeneous, thermoreversible gel containing reduced viscosity carrageenan and products made therefrom | |
| US20050019294A1 (en) | Homogeneous, thermoreversible alginate films and soft capsules made therefrom | |
| US20150119470A1 (en) | Compounding and extruding method for producing starch softgel capsules | |
| ZA200508251B (en) | Homogeneous, thermoreversible gel film containing kappa-2 carrageenan and soft capsules made therefrom | |
| US20050019295A1 (en) | Homogeneous, thermoreversible low viscosity polymannan gum films and soft capsules made therefrom | |
| JP2004315466A (en) | Coating composition for capsule | |
| CA2872052C (en) | Coating and extruding method for producing starch softgel capsules | |
| US20120312449A1 (en) | Band seal-preparation liquid viscometer for capsules | |
| CA2872049A1 (en) | Compounding and extruding method for producing starch softgel capsules |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20220301 |
|
| MKLA | Lapsed |
Effective date: 20200831 |