CA2344678C - Semi-moist oral delivery system - Google Patents
Semi-moist oral delivery system Download PDFInfo
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- CA2344678C CA2344678C CA002344678A CA2344678A CA2344678C CA 2344678 C CA2344678 C CA 2344678C CA 002344678 A CA002344678 A CA 002344678A CA 2344678 A CA2344678 A CA 2344678A CA 2344678 C CA2344678 C CA 2344678C
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- Prior art keywords
- additive
- composition
- starch
- water
- sucrose
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Classifications
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- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
Abstract
These and other objects are attained by the subject invention wherein there is provided a carrier or product formed of a matrix having starch, sugar, fat, polyhydric alcohol and water in suitable ratios such that there exists a water activity of 0.6-0.75. The water activity of the product matrix is adjusted up or down so that the availability of water in the finished product is not detrimental to the included active ingredient, be it pharmaceutical, nutraceutical, or a vitamin mineral complex.
Description
This application is directed to a means for delivering pharmaceuticals, nutraceuticals and the like to a mammal and more specifically, the control of the water activity of a food product matrix for use in the incorporation of a pharmaceutical, nutraceutical or other bioactive compound into the matrix.
Pharmaceutical and nutraceutical products intended for oral administration are typically provided in tablet, capsule, pill, lozenges and caplet form.
These products are swallowed whole or chewed in the mouth for delivery of the active ingredient into the alimentary system of a body. Such oral delivery systems are sometimes made chewable to ease drug administration in pediatric and geriatric patients. Such concerns with ease of administration may be amplified when dealing with pets and other animals.
As a result, several approaches have been utilized in formulating oral delivery systems, including gums and candy bases. The use of such delivery systems is limited by the reaction of the active ingredient, whether it be pharmaceutical, nutraceutical or other ingredients, to the existence of water in the system.
Therefore, an object of the subject invention is a method of controlling water activity in an oral delivery system and the product thereof.
A further object of the subject invention is a oral delivery system for pharmaceuticals, nutraceuticals or other active ingredient which matches the water activity of the carrier to the included active ingredient.
Pharmaceutical and nutraceutical products intended for oral administration are typically provided in tablet, capsule, pill, lozenges and caplet form.
These products are swallowed whole or chewed in the mouth for delivery of the active ingredient into the alimentary system of a body. Such oral delivery systems are sometimes made chewable to ease drug administration in pediatric and geriatric patients. Such concerns with ease of administration may be amplified when dealing with pets and other animals.
As a result, several approaches have been utilized in formulating oral delivery systems, including gums and candy bases. The use of such delivery systems is limited by the reaction of the active ingredient, whether it be pharmaceutical, nutraceutical or other ingredients, to the existence of water in the system.
Therefore, an object of the subject invention is a method of controlling water activity in an oral delivery system and the product thereof.
A further object of the subject invention is a oral delivery system for pharmaceuticals, nutraceuticals or other active ingredient which matches the water activity of the carrier to the included active ingredient.
~PCr~j~~tion of the Preferre Embodiment By the subject invention, a soft chewable oral delivery system is provided. The dosage form may be in tablet form and may contain one or more active ingredients. The active ingredients are incorporated into the system which is described in further detail below and which includes a starch component, a fat or oil, a sugar component, a polyhydric alcohol, water and other minor ingredients.
Into this mixture is placed the active ingredient. After mixing and extruding these ingredients, the extrudate is formed into the appropriate shape. The relative proportions of the mixture are as follows.
Starch 10-50 %
Fat or Oil 0-40 Sugar 5-25 Polyhydric Alcohol 10-50 Water 5-20%
Salt (NaCI) 1-5 %
Active Ingredient 0.1-5 %
Generally speaking, the starch component of the matrix comprises 10 to SO percent by weight of the matrix. More particularly, the starch component of the matrix comprises 15 to 40 percent by weight of the matrix.
While starch for use in the matrix can be of any suitable type, it is most preferred that at least part of the starch in the matrix be a highly derivatized or pregelatinized starch. If a highly derivatized starch is present in the matrix, it should be present in an amount of about 1/2 percent by weight of the total starch and the WO OO/1b743 PCT/US99/20547 balance of the starch being non-derivatized. More preferably, about 20-X1.0 percent by weight of the total matrix and about 45 % of the total starch should be the derivatized starch. An exaznpie of a preferred pregelatinized starch is A.E. Staley's NU-COL
4227 or SOFT-SET.
Other amylaceous ingredients may be used in combination with the derivatized starch or alone, provided the starch limits are not exceeded. The amylaceous ingredients can be gelatinized or cooked before or during the forming step to achieve the desired matrix characteristics. If gelatinized starch is used, it may be possible to prepare the product of the subject invention or perform the method of the subject invention without heating or cooking of any son. However, if ungelatinized (ungelled) or uncooked starch is used, the matrix must be cooked sufficiently to gel or cook the starch to reach the desired content.
Starches that can serve as a base starch for derivatization include regular corn, waxy corn, potato, tapioca, rice, etc. Such types of derivatizing agents for the starch include but are not limited to ethylene oxide, propylene oxide, acetic anhydride, and succinic anhydride, and other food approved esters or ethers, introducing such chemicals alone or in combination with one another. Prior crosslinking of the starch may or may not be necessary based on the pH of the system and the temperature used to form the product.
By "amylaceous ingredients" is meant those food-stuffs containing a preponderance of starch and/or starch-like material. Examples of amylaceous ingredients are cereal grains and meals or flours obtained upon grinding cereal grains such as corn, oats, wheat, milo, barley, rice, and the various milling by-products of these cereal grains such as wheat feed flour, wheat middlings, mixed feed, wheat _ shorts, wheat red dog, oat groats, hominy feed, and other such material.
Also included as sources of amylaceous ingredients are the tuberous food stuffs such as potatoes, tapioca, and the like.
Another component of the matrix is a fat component such as fat or oil of animal or vegetable origin. Typical animal fats or oils are fish oil, chicken fat, tallow, choice white grease, prime steam lard and mixtures thereof. Other animal fats are also suitable for use in the matrix. Vegetable fats or oils are derived from corn, soy, cottonseed, peanut, flax, rapeseed, sunflower, other oil bearing vegetable seeds, and mixtures thereof. Additionally, a mixture of animal or vegetable oils or fats is suitable for use in the matrix. The fat component of the mauix is about 0 to about 40 % by weight of the matrix. More specifically, the fat component of the matxix is about 20 percent by weight of the matrix.
The poiyhydric alcohol component of the matrix can be selected from glycerol, sorbitol, propylene glycol, 1.3-butanediol, and mixtures thereof with each other and other polyhydric alcohols. Generally the polyhydric alcohol comprises about 10 to about 50 percent by weight of the matrix. More specifically, the polyhydric alcohol comprises about 20 to about 40 percent by weight of the matrix.
The sugar component can be employed in a dry or crystalline condition or can be an aqueous syrup having a sugar concentration of from 50 to about 95, preferably from 70 to about 80, weight percent. The sugar used can be lactose, sucrose, fructose, glucose, or maltose, depending on the particular application and price or availability of a particular sugar. Examples of various well established sources of these sugars are, corn syrup solids, malt syrup, hydrolyzed corn starch, hydrol (syrup from glucose manufacturing operations), raw and refined cane and beet sugars, etc.
Water must be present in the matrix at least about 5 percent by weight of the matrix. More specifically, water is present in the matrix about 5 percent to about 20 percent by weight of the matrix. The matrix thus formed usually has a water 5 activity of 0.60 to 0.75.
While water must be at least 5 percent by weight of the matrix, when the matrix is used in a food product, the moisture of the food product must be adjusted. Generally the moisture content of the matrix is such to give a moisture content of 5-15 percent to the final soft dry food product. More preferred is a moisture content of 5 percent to 14 percent. Most preferred is a moisture content of 8 percent to 13 percent. The desired moisture content may be achieved in any suitable fashion. Normal processing may produce the moisture content desired. A
standard drying step is optional and may be used if necessary.
The active ingredient may be any drug, nutrition agent, or the like which can be orally administered. Exemplary of such active ingredients are the flowing: nutraceuticals, such as chromium picolinate, potassium gluconate and methionine amino acid; prescription drugs, such as ivermectin, fenbendazole, piperazine, magnesium hydroxide, stranozole, furosemide, penicillin, amoxicillin, prednisolone, methylprednisolone, acepromazine; and, other pharmaceutical products, such as aspirin, prozac, zantac, and benedryl. Minor amounts of flavorants, colorants, glycerin, flavor enhancers, sweeteners, emulsifiers, antibitterness agents, taste masking agents, stabilizers, preservatives, or combinations thereof may be added.
To form the matrix, the starch system, fat, polyhydric alcohol, corn syrup and water are mixed with a screw extruder, permitting addition of ingredients and variable heating at different points along the barrel. Other mixing apparatus, such as a sigma mixer, swept wall heat exchanger or the like may be used. If a coloration is desired in the final product, cooked or pregelled starches are used to form the matrix. The use of these starches avoids high cooking temperatures which would destroy the desire coloration andior active ingredient. If coloration active temperature sensitivity is not a problem, it is possible to use an uncooked or ungelatinized starch to form the matrix and cook or gel the starch as the process is carried out.
The incorporation of a derivatized starch in the product more clearly guarantees the softness of the product for a longer period of time. ~ofmess is also provided by the fats and oils. In this fashion a suitable matrix is provided for use with a wide variety of active ingredients.
Having fully described the invention, the following examples are presented to illustrate the invention without limitation thereof. In these examples all parts percentages are by weight unless otherwise specified.
Into this mixture is placed the active ingredient. After mixing and extruding these ingredients, the extrudate is formed into the appropriate shape. The relative proportions of the mixture are as follows.
Starch 10-50 %
Fat or Oil 0-40 Sugar 5-25 Polyhydric Alcohol 10-50 Water 5-20%
Salt (NaCI) 1-5 %
Active Ingredient 0.1-5 %
Generally speaking, the starch component of the matrix comprises 10 to SO percent by weight of the matrix. More particularly, the starch component of the matrix comprises 15 to 40 percent by weight of the matrix.
While starch for use in the matrix can be of any suitable type, it is most preferred that at least part of the starch in the matrix be a highly derivatized or pregelatinized starch. If a highly derivatized starch is present in the matrix, it should be present in an amount of about 1/2 percent by weight of the total starch and the WO OO/1b743 PCT/US99/20547 balance of the starch being non-derivatized. More preferably, about 20-X1.0 percent by weight of the total matrix and about 45 % of the total starch should be the derivatized starch. An exaznpie of a preferred pregelatinized starch is A.E. Staley's NU-COL
4227 or SOFT-SET.
Other amylaceous ingredients may be used in combination with the derivatized starch or alone, provided the starch limits are not exceeded. The amylaceous ingredients can be gelatinized or cooked before or during the forming step to achieve the desired matrix characteristics. If gelatinized starch is used, it may be possible to prepare the product of the subject invention or perform the method of the subject invention without heating or cooking of any son. However, if ungelatinized (ungelled) or uncooked starch is used, the matrix must be cooked sufficiently to gel or cook the starch to reach the desired content.
Starches that can serve as a base starch for derivatization include regular corn, waxy corn, potato, tapioca, rice, etc. Such types of derivatizing agents for the starch include but are not limited to ethylene oxide, propylene oxide, acetic anhydride, and succinic anhydride, and other food approved esters or ethers, introducing such chemicals alone or in combination with one another. Prior crosslinking of the starch may or may not be necessary based on the pH of the system and the temperature used to form the product.
By "amylaceous ingredients" is meant those food-stuffs containing a preponderance of starch and/or starch-like material. Examples of amylaceous ingredients are cereal grains and meals or flours obtained upon grinding cereal grains such as corn, oats, wheat, milo, barley, rice, and the various milling by-products of these cereal grains such as wheat feed flour, wheat middlings, mixed feed, wheat _ shorts, wheat red dog, oat groats, hominy feed, and other such material.
Also included as sources of amylaceous ingredients are the tuberous food stuffs such as potatoes, tapioca, and the like.
Another component of the matrix is a fat component such as fat or oil of animal or vegetable origin. Typical animal fats or oils are fish oil, chicken fat, tallow, choice white grease, prime steam lard and mixtures thereof. Other animal fats are also suitable for use in the matrix. Vegetable fats or oils are derived from corn, soy, cottonseed, peanut, flax, rapeseed, sunflower, other oil bearing vegetable seeds, and mixtures thereof. Additionally, a mixture of animal or vegetable oils or fats is suitable for use in the matrix. The fat component of the mauix is about 0 to about 40 % by weight of the matrix. More specifically, the fat component of the matxix is about 20 percent by weight of the matrix.
The poiyhydric alcohol component of the matrix can be selected from glycerol, sorbitol, propylene glycol, 1.3-butanediol, and mixtures thereof with each other and other polyhydric alcohols. Generally the polyhydric alcohol comprises about 10 to about 50 percent by weight of the matrix. More specifically, the polyhydric alcohol comprises about 20 to about 40 percent by weight of the matrix.
The sugar component can be employed in a dry or crystalline condition or can be an aqueous syrup having a sugar concentration of from 50 to about 95, preferably from 70 to about 80, weight percent. The sugar used can be lactose, sucrose, fructose, glucose, or maltose, depending on the particular application and price or availability of a particular sugar. Examples of various well established sources of these sugars are, corn syrup solids, malt syrup, hydrolyzed corn starch, hydrol (syrup from glucose manufacturing operations), raw and refined cane and beet sugars, etc.
Water must be present in the matrix at least about 5 percent by weight of the matrix. More specifically, water is present in the matrix about 5 percent to about 20 percent by weight of the matrix. The matrix thus formed usually has a water 5 activity of 0.60 to 0.75.
While water must be at least 5 percent by weight of the matrix, when the matrix is used in a food product, the moisture of the food product must be adjusted. Generally the moisture content of the matrix is such to give a moisture content of 5-15 percent to the final soft dry food product. More preferred is a moisture content of 5 percent to 14 percent. Most preferred is a moisture content of 8 percent to 13 percent. The desired moisture content may be achieved in any suitable fashion. Normal processing may produce the moisture content desired. A
standard drying step is optional and may be used if necessary.
The active ingredient may be any drug, nutrition agent, or the like which can be orally administered. Exemplary of such active ingredients are the flowing: nutraceuticals, such as chromium picolinate, potassium gluconate and methionine amino acid; prescription drugs, such as ivermectin, fenbendazole, piperazine, magnesium hydroxide, stranozole, furosemide, penicillin, amoxicillin, prednisolone, methylprednisolone, acepromazine; and, other pharmaceutical products, such as aspirin, prozac, zantac, and benedryl. Minor amounts of flavorants, colorants, glycerin, flavor enhancers, sweeteners, emulsifiers, antibitterness agents, taste masking agents, stabilizers, preservatives, or combinations thereof may be added.
To form the matrix, the starch system, fat, polyhydric alcohol, corn syrup and water are mixed with a screw extruder, permitting addition of ingredients and variable heating at different points along the barrel. Other mixing apparatus, such as a sigma mixer, swept wall heat exchanger or the like may be used. If a coloration is desired in the final product, cooked or pregelled starches are used to form the matrix. The use of these starches avoids high cooking temperatures which would destroy the desire coloration andior active ingredient. If coloration active temperature sensitivity is not a problem, it is possible to use an uncooked or ungelatinized starch to form the matrix and cook or gel the starch as the process is carried out.
The incorporation of a derivatized starch in the product more clearly guarantees the softness of the product for a longer period of time. ~ofmess is also provided by the fats and oils. In this fashion a suitable matrix is provided for use with a wide variety of active ingredients.
Having fully described the invention, the following examples are presented to illustrate the invention without limitation thereof. In these examples all parts percentages are by weight unless otherwise specified.
F;~jpl,~.1-- Carrier INGREDIENT PARTS
Regular Corn Starch (Purefood 1$.0 GMI) Pregel Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup 15.0 Solids) Corn Oil 20.0 Sorbitol 20.0 H20 10.0 Salt 2.0 TOTAL 100.0 The above ingredients are mined at temperatures of about 125°F, S extruded and cut into a suitable tablet size. This product has an oily, bubbly appearance suggesting cutting back on the oil content. Temperature was also adjusted during each of the following examples to eliminate puffing of the product as it exits the extruder.
- Guaifenesin INGREDIENT PARTS
Regular Corn Starch (Purefood 17.9 GMI) Pregel Starch {SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup 15.0 Solids) Sorbitol 39.3 HZO 10.0 I Salt I 2.0 Guaifenesin* 0.8 TOTAL 100.0 * Available from Arrow Chemical Co., PLE -- Vitamins INGREDIENT PARTS
Regular Corn Starch (Purefood 17.9 GMI) Pregel Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup 15.0 Solids) Sorbitol 35.1 g20 10.0 sat z.o Vitamin and Mineral Mix* 5.0 TOTAL 100.0 * Commercially available mizcure available from Archer Daniels Midland.
-- Flax INGREDIENT PARTS
Regular Corn Starch (Purefood 17.9 GMI) Pregel Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup 15.0 Solids) Sorbitol 35.1 H2p 10.0 Salt 2.0 Flax* 5.0 TOTAL 100.0 ~Avvlable nom l;nreco rlax.
WO 00/16743 PCT/US99/20547 .
E~pl,E~ -- Acetaminophen INGREDIENT PERCENT
Regular Corn Starch (Purefood 17.9 GMI) Pregel Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup 15.0 Solids) Sorbitol 39.1 g2p 10.0 Salt 2.0 Acetaminophen* 0.8 Red Coloring #40 0.1 Flavoring (Cherry) 0.1 TOTAL 100.0 * Available from Mallincrodt as c:otnpap RXAME~ 6 -- Carrier INGREDIENT PARTS
Regular Corn Starch (Purefood 17.9 GMI) Pregel Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup 15.0 Solids) Sorbitol 40.1 g2p 10.0 Salt 2.0 TOTAL 100.0 Example Active Oil/Sugar Aw Extrusion Temp.
1 Premix Corn Oil/SorbitolNIA 125 2 Guaifenesin 100 % Sorbitol 0.656 115 3 Vitamin Mix 100% Sorbitol 0.651 115 4 Flax 100 % Sorbitol 0.673 115 5 Acetaminophen 100% Sorbitol 0.666 115 6 Premix 100 % Sorbitol 0.61 115 By the above examples and Table 1 it is apparent that an oral delivery system for the administration for pharmaceuticals, nutraceuticals, vitamins and 5 minerals and other active ingredients may be provided in a chewable form by the subject invention. If the active ingredient is water sensitive such as aspirin, then the amount of polyhydric alcohol is increased, the water activity is depressed to about 0.65 and the stability and texture of the resultant product is maintained. If the active ingredient requires or can tolerate the presence of free water for its activity, such as in 10 the case of Guaifenesin, the amount of polyhydric alcohol may be decreased, while maintaining the level of such polyhydric alcohol such that a soft texture of the resulting tablet is maintained. In the case of Guaifenesin, then an AW of 0.70 may be utilized and a softer, more chewable texture achieved. An effective oral delivery system in which the texture and stability of the product and activity of the active ingredient is controllable, is the result.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments and equivalents falling within the scope of the appended claims.
Various features of the invention are set forth in the following claims.
Regular Corn Starch (Purefood 1$.0 GMI) Pregel Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup 15.0 Solids) Corn Oil 20.0 Sorbitol 20.0 H20 10.0 Salt 2.0 TOTAL 100.0 The above ingredients are mined at temperatures of about 125°F, S extruded and cut into a suitable tablet size. This product has an oily, bubbly appearance suggesting cutting back on the oil content. Temperature was also adjusted during each of the following examples to eliminate puffing of the product as it exits the extruder.
- Guaifenesin INGREDIENT PARTS
Regular Corn Starch (Purefood 17.9 GMI) Pregel Starch {SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup 15.0 Solids) Sorbitol 39.3 HZO 10.0 I Salt I 2.0 Guaifenesin* 0.8 TOTAL 100.0 * Available from Arrow Chemical Co., PLE -- Vitamins INGREDIENT PARTS
Regular Corn Starch (Purefood 17.9 GMI) Pregel Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup 15.0 Solids) Sorbitol 35.1 g20 10.0 sat z.o Vitamin and Mineral Mix* 5.0 TOTAL 100.0 * Commercially available mizcure available from Archer Daniels Midland.
-- Flax INGREDIENT PARTS
Regular Corn Starch (Purefood 17.9 GMI) Pregel Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup 15.0 Solids) Sorbitol 35.1 H2p 10.0 Salt 2.0 Flax* 5.0 TOTAL 100.0 ~Avvlable nom l;nreco rlax.
WO 00/16743 PCT/US99/20547 .
E~pl,E~ -- Acetaminophen INGREDIENT PERCENT
Regular Corn Starch (Purefood 17.9 GMI) Pregel Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup 15.0 Solids) Sorbitol 39.1 g2p 10.0 Salt 2.0 Acetaminophen* 0.8 Red Coloring #40 0.1 Flavoring (Cherry) 0.1 TOTAL 100.0 * Available from Mallincrodt as c:otnpap RXAME~ 6 -- Carrier INGREDIENT PARTS
Regular Corn Starch (Purefood 17.9 GMI) Pregel Starch (SOFT SET) 15.0 Corn Syrup (Star Dri Corn Syrup 15.0 Solids) Sorbitol 40.1 g2p 10.0 Salt 2.0 TOTAL 100.0 Example Active Oil/Sugar Aw Extrusion Temp.
1 Premix Corn Oil/SorbitolNIA 125 2 Guaifenesin 100 % Sorbitol 0.656 115 3 Vitamin Mix 100% Sorbitol 0.651 115 4 Flax 100 % Sorbitol 0.673 115 5 Acetaminophen 100% Sorbitol 0.666 115 6 Premix 100 % Sorbitol 0.61 115 By the above examples and Table 1 it is apparent that an oral delivery system for the administration for pharmaceuticals, nutraceuticals, vitamins and 5 minerals and other active ingredients may be provided in a chewable form by the subject invention. If the active ingredient is water sensitive such as aspirin, then the amount of polyhydric alcohol is increased, the water activity is depressed to about 0.65 and the stability and texture of the resultant product is maintained. If the active ingredient requires or can tolerate the presence of free water for its activity, such as in 10 the case of Guaifenesin, the amount of polyhydric alcohol may be decreased, while maintaining the level of such polyhydric alcohol such that a soft texture of the resulting tablet is maintained. In the case of Guaifenesin, then an AW of 0.70 may be utilized and a softer, more chewable texture achieved. An effective oral delivery system in which the texture and stability of the product and activity of the active ingredient is controllable, is the result.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments and equivalents falling within the scope of the appended claims.
Various features of the invention are set forth in the following claims.
Claims (23)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A composition for the oral administration of an additive to mammals in a discrete dosage form, said composition comprising:
an additive selected from the group consisting of pharmaceutical, nutritional supplements, vitamins, minerals, and mixtures thereof, an extrudate comprising a matrix having about 10 to about 50% wt starch, a sweetener consisting essentially of sucrose, corn syrup and polyhydric alcohol, said sucrose being in an amount of at least 10%, and at least about 5% wt water, said composition having A w of about 0.60 to about 0.75, and a soft and chewy texture, and said A w being adjusted to permit an appropriate amount of free water in the presence of the additive.
an additive selected from the group consisting of pharmaceutical, nutritional supplements, vitamins, minerals, and mixtures thereof, an extrudate comprising a matrix having about 10 to about 50% wt starch, a sweetener consisting essentially of sucrose, corn syrup and polyhydric alcohol, said sucrose being in an amount of at least 10%, and at least about 5% wt water, said composition having A w of about 0.60 to about 0.75, and a soft and chewy texture, and said A w being adjusted to permit an appropriate amount of free water in the presence of the additive.
2. The composition of claim 1 wherein the water content is about 10%.
3. The composition of claim 1 wherein the polyhydric alcohol content is about 40%.
4. The composition of claim 1 wherein the starch content is about 32%.
5. The composition of claim 1 wherein said composition has a pregelatinized starch content of about 15%.
6. The composition of claim 1 where the A w is 0.65 and the additive is aspirin.
7. The composition of claim 1 wherein the polyhydric alcohol is sorbitol.
8. The composition of claim 1 wherein the sucrose content is about 15%.
9. A method of making a carrier and additive mixture for use in an oral administration of a therapeutically effective amount of the additive in a discrete dosage form, comprising the steps of:
a) forming a matrix and additive admixture by mixing, in a one-step procedure said additive, about 10 to about 50% wt starch, 0 to about 40% wt fat or oil, a sweetener consisting of sucrose, corn syrup and polyhydric alcohol, said sucrose being in an amount of at least 10%, and water, and mixing;
adjusting the relative amounts of polyhydric alcohol and water to control the A w of said admixture to adjust the level of moisture in the carrier to be a level not inimical to the additive; and extruding said admixture to form an extrudate.
a) forming a matrix and additive admixture by mixing, in a one-step procedure said additive, about 10 to about 50% wt starch, 0 to about 40% wt fat or oil, a sweetener consisting of sucrose, corn syrup and polyhydric alcohol, said sucrose being in an amount of at least 10%, and water, and mixing;
adjusting the relative amounts of polyhydric alcohol and water to control the A w of said admixture to adjust the level of moisture in the carrier to be a level not inimical to the additive; and extruding said admixture to form an extrudate.
10. The method of claim 9 including adjusting the water content to about 10%.
11. The method of claim 9 including adjusting the polyhydric alcohol content to about 40%.
12. The method of claim 9 including adjusting the starch content to about 32%.
13. The method of claim 9 including adjusting the sucrose content to about 15%.
14. The method of claim 9 further comprising adding pregelatinized starch to about 15%
of the mixture.
of the mixture.
15. The method of claim 9 wherein said additive is a pharmaceutical.
16. The method of claim 9 wherein said additive is a nutraceutical.
17. The method of claim 9 wherein said additive is a vitamin and mineral mix.
18. The method of claim 9 wherein said polyhydric alcohol is sorbitol.
19. The method of claim 9 wherein the A w is about 0.60 to about 0.75.
20. The method of claim 9 wherein the additive is aspirin and the A w is about 0.65.
21. The composition of claim 2 wherein the additive constitutes from about 0.1% to about 5.0%of the composition.
22. The method of claim 9 wherein the additive is in an amount of about 0.1%
to about 5.0% of the mixture.
to about 5.0% of the mixture.
23. A composition for the oral administration of a pharmaceutical additive to mammals in a discrete dosage form, said discrete dosage form comprising:
a pharmaceutical additive;
an extrudate having a matrix, and comprising:
10-50% starch, 0-40% fat or oil, a sweetener consisting essentially of sucrose, corn syrup and sorbitol, said sucrose being in an amount of least 10%, at least about 5% water, said composition having an A w of about 0.60 to about 0.75, and a soft and chewy texture, and said A w being adjusted to permit an appropriate amount of free water in the presence of the additive.
a pharmaceutical additive;
an extrudate having a matrix, and comprising:
10-50% starch, 0-40% fat or oil, a sweetener consisting essentially of sucrose, corn syrup and sorbitol, said sucrose being in an amount of least 10%, at least about 5% water, said composition having an A w of about 0.60 to about 0.75, and a soft and chewy texture, and said A w being adjusted to permit an appropriate amount of free water in the presence of the additive.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/160,618 US6387381B2 (en) | 1998-09-24 | 1998-09-24 | Semi-moist oral delivery system |
| US09/160,618 | 1998-09-24 | ||
| PCT/US1999/020547 WO2000016743A1 (en) | 1998-09-24 | 1999-09-07 | Semi-moist oral delivery system |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2344678A1 CA2344678A1 (en) | 2000-03-30 |
| CA2344678C true CA2344678C (en) | 2007-04-24 |
Family
ID=22577644
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002344678A Expired - Fee Related CA2344678C (en) | 1998-09-24 | 1999-09-07 | Semi-moist oral delivery system |
Country Status (5)
| Country | Link |
|---|---|
| US (3) | US6387381B2 (en) |
| EP (1) | EP1115377A4 (en) |
| AU (1) | AU744737B2 (en) |
| CA (1) | CA2344678C (en) |
| WO (1) | WO2000016743A1 (en) |
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| DE10031044A1 (en) | 2000-06-26 | 2002-01-03 | Bayer Ag | Endoparasiticidal agents for voluntary oral ingestion by animals |
| US6753004B2 (en) * | 2001-09-04 | 2004-06-22 | Auburn University | Biodegradable fishing lure and material |
| US20040013732A1 (en) * | 2001-09-25 | 2004-01-22 | Michael Farber | Starch-based delivery system for creatine |
| US7067150B2 (en) | 2002-04-16 | 2006-06-27 | Scepter Holdings, Inc. | Delivery systems for functional ingredients |
| WO2004014143A1 (en) * | 2002-08-13 | 2004-02-19 | Akzo Nobel | Compositions and process for delivering an additive |
| US20040037869A1 (en) | 2002-08-16 | 2004-02-26 | Douglas Cleverly | Non-animal product containing veterinary formulations |
| US20040091579A1 (en) * | 2002-11-13 | 2004-05-13 | Rubicon Scientific Llc; | Extruded foodstuffs having maintenance level actives |
| WO2005084634A1 (en) * | 2003-06-13 | 2005-09-15 | Scepter Holdings, Inc. | Delivery systems for non-steroidal anti-inflammatory drugs (nsaids) |
| TWI366442B (en) † | 2003-07-30 | 2012-06-21 | Novartis Ag | Palatable ductile chewable veterinary composition |
| US20080160086A1 (en) * | 2004-02-19 | 2008-07-03 | Scepter Holdings, Inc. | Delivery Systems For Calcium |
| JP2007532571A (en) * | 2004-04-07 | 2007-11-15 | インターベツト・インターナシヨナル・ベー・ベー | Effective compositions of benzimidazole, avermectin and praziquantel and related methods of use |
| WO2005097085A1 (en) * | 2004-04-08 | 2005-10-20 | Micro Nutrient, Llc | Nutrient system for individualized responsive dosing regimens |
| US7850987B2 (en) * | 2004-04-08 | 2010-12-14 | Micronutrient, Llc | Nutrient composition(s) and system(s) for individualized, responsive dosing regimens |
| US7785619B2 (en) * | 2004-04-08 | 2010-08-31 | Micro Nutrient, Llc | Pharmanutrient composition(s) and system(s) for individualized, responsive dosing regimens |
| US7318920B2 (en) * | 2004-09-27 | 2008-01-15 | Ez-Med Company | Low water activity nutritional product having beneficial microbial and high oil content |
| FR2896958B1 (en) * | 2006-02-07 | 2012-09-14 | Vetinnov | SUPPORT APPEALS TO AN IMPROVED FORMULA. |
| US7767248B2 (en) * | 2007-02-02 | 2010-08-03 | Overly Iii Harry J | Soft chew confectionary with high fiber and sugar content and method for making same |
| US20090011079A1 (en) * | 2007-07-02 | 2009-01-08 | Bestsweet, Inc. | Hard Coated Confectionary Having A Consumable Soft Chewing Core With An Active And Method For Making Same |
| US8697174B2 (en) | 2010-01-27 | 2014-04-15 | Ainsworth Pet Nutrition | Treats and methods for producing same |
| WO2014033230A1 (en) | 2012-08-31 | 2014-03-06 | Friulchem Spa | Compositions for oral administration to animals, production methods thereof and uses of same |
| ES2666868T3 (en) | 2011-09-15 | 2018-05-08 | Friulchem Spa | Compositions for oral administration to animals and method of obtaining |
| WO2013068371A1 (en) | 2011-11-08 | 2013-05-16 | Intervet International B.V. | Soft chewable dosage form compositions of cannabinoid receptor type 1 (cb-1) antagonists |
| NZ719079A (en) | 2012-02-06 | 2017-09-29 | Merial Inc | Parasiticidal oral veterinary compositions comprising systemically-acting active agents, methods and uses thereof |
| US20150057321A1 (en) | 2012-04-04 | 2015-02-26 | Intervet Inc. | Soft chewable pharmaceutical products |
| EP2838377A4 (en) | 2012-04-17 | 2016-04-20 | Big Heart Pet Brands | Appetizing and dentally efficacious animal chews |
| US9532946B2 (en) | 2012-11-20 | 2017-01-03 | Intervet Inc. | Manufacturing of semi-plastic pharmaceutical dosage units |
| CN111803465B (en) * | 2013-03-15 | 2023-05-09 | 阿根塔创新有限公司 | Chewable formulation |
| US9808010B2 (en) | 2015-07-06 | 2017-11-07 | Virbac Corporation | Chewable composition |
| ES2947367T3 (en) | 2017-07-26 | 2023-08-07 | Tgx Soft Chew Llc | Non-starchy soft chew for veterinary applications |
| EA202191063A1 (en) | 2018-10-18 | 2021-07-12 | Джонсон энд Джонсон Консьюмер Инк. | NEW DOSE FORM |
| US20220160628A1 (en) * | 2020-11-24 | 2022-05-26 | Florida Research Group Llc | Process for manufacturing improved semi-soft solid dosage forms and soft chews produced thereby |
| EP4263559A1 (en) | 2020-12-18 | 2023-10-25 | Boehringer Ingelheim Animal Health USA Inc. | Boron containing pyrazole compounds, compositions comprising them, methods and uses thereof |
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| US5266333A (en) | 1985-03-06 | 1993-11-30 | American Cyanamid Company | Water dispersible and water soluble carbohydrate polymer compositions for parenteral administration of growth hormone |
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| WO1995007622A1 (en) * | 1993-09-15 | 1995-03-23 | Wm. Wrigley Jr. Company | Hard coated chewing gum with improved shelf life, with mixed polyol coatings |
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| WO1998023165A1 (en) * | 1996-11-27 | 1998-06-04 | Wm. Wrigley Jr. Company | Method of controlling release of caffeine in chewing gum and gum produced thereby |
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| US5928664A (en) * | 1998-02-11 | 1999-07-27 | Fuisz Technologies Ltd. | Consumable gummy delivery system |
| AU747549B2 (en) | 1998-03-23 | 2002-05-16 | General Mills Inc. | Encapsulation of components into edible products |
-
1998
- 1998-09-24 US US09/160,618 patent/US6387381B2/en not_active Ceased
-
1999
- 1999-09-07 CA CA002344678A patent/CA2344678C/en not_active Expired - Fee Related
- 1999-09-07 EP EP99969328A patent/EP1115377A4/en not_active Withdrawn
- 1999-09-07 AU AU60294/99A patent/AU744737B2/en not_active Ceased
- 1999-09-07 WO PCT/US1999/020547 patent/WO2000016743A1/en active IP Right Grant
-
2003
- 2003-08-13 US US10/639,909 patent/USRE41108E1/en not_active Expired - Lifetime
-
2009
- 2009-04-29 US US12/426,396 patent/USRE43582E1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US20010036464A1 (en) | 2001-11-01 |
| USRE43582E1 (en) | 2012-08-14 |
| US6387381B2 (en) | 2002-05-14 |
| EP1115377A1 (en) | 2001-07-18 |
| AU744737B2 (en) | 2002-02-28 |
| USRE41108E1 (en) | 2010-02-09 |
| AU6029499A (en) | 2000-04-10 |
| CA2344678A1 (en) | 2000-03-30 |
| WO2000016743A1 (en) | 2000-03-30 |
| EP1115377A4 (en) | 2009-04-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |