CA1164800A - Vitamin encapsulation - Google Patents
Vitamin encapsulationInfo
- Publication number
- CA1164800A CA1164800A CA000389651A CA389651A CA1164800A CA 1164800 A CA1164800 A CA 1164800A CA 000389651 A CA000389651 A CA 000389651A CA 389651 A CA389651 A CA 389651A CA 1164800 A CA1164800 A CA 1164800A
- Authority
- CA
- Canada
- Prior art keywords
- droplets
- alginate
- alcohol
- vitamin
- oil
- 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
Links
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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- B01J13/08—Simple coacervation, i.e. addition of highly hydrophilic material
Abstract
VITAMIN ENCAPSULATION
Abstract of the Disclosure Disclosed is a process for encapsulating oils and oil-soluble substances in multi-compartmentalized, mechanically stable microcapsules. The process comprises the steps of first forming an emulsion consisting of a continuous phase comprising an aqueous solution of an alkali metal alginate and optionally a water-soluble, alcohol-insoluble filler such as a polysaccharide, and a dispersed phase of an oleophilic substance such as one or more vitamins dissolved in an oil. The emulsion is then formed into droplets which are thereafter immersed in an alcoholic solu-tion of multivalent cations, to produce a shape-retaining algi-nate matrix filled with precipitated polysaccharide and enclosing plural oil droplets. The vitamins are thereby protected from oxidative degradation and can be handled like conventional crystalline solids.
Abstract of the Disclosure Disclosed is a process for encapsulating oils and oil-soluble substances in multi-compartmentalized, mechanically stable microcapsules. The process comprises the steps of first forming an emulsion consisting of a continuous phase comprising an aqueous solution of an alkali metal alginate and optionally a water-soluble, alcohol-insoluble filler such as a polysaccharide, and a dispersed phase of an oleophilic substance such as one or more vitamins dissolved in an oil. The emulsion is then formed into droplets which are thereafter immersed in an alcoholic solu-tion of multivalent cations, to produce a shape-retaining algi-nate matrix filled with precipitated polysaccharide and enclosing plural oil droplets. The vitamins are thereby protected from oxidative degradation and can be handled like conventional crystalline solids.
Description
1 BacXground of the Invention This invention relates to a method of encapsulating oils and oil-soluble materials, such as vitamins A, D, and E, which dispenses with the use of gelatins. More particularly, it relates to a method of producing ingestible microcapsules comprising a matrix of substantially water-insoluble shape-retaining alginate gel held together by salt bridges between the carboxyl groups of the alginate.
There are many known prior art methods of encap-sulating oleophilic substances. Methods of encapsulating oil-soluble vitamin6 are disclosed, for example, in U.S. Patent Nos.
There are many known prior art methods of encap-sulating oleophilic substances. Methods of encapsulating oil-soluble vitamin6 are disclosed, for example, in U.S. Patent Nos.
2,183,053; 2,218,591; 2,643,209; 2,650,895; 2,897,119; 3,058,728;
3,0g9,602; 3,202,731; 3,293,132; 3,608,083; 3,749,799; 3,819,838;
and 3,143,475. The vast majority of these and other vitamin encapsulating procedure6 involve the use of gelatins which are solidified about droplets of vitamin oil~ by rapidly lowering the temperature and subsequent dehydration.
While methods such as those disclosed in the patent literature set forth above have achieved ~ome 6ignificant com-mercial success, difficulties have sometimes been encountered inrapidly inducing solidification of the encapsulating material.
Furthermore, substantial quantities of heat are normally required in the course of gelatin-based proces~es in order to effectively dissolve the gelatin and to dehydrate the cap6ules produced.
I
, . , 1 Summary of the Invention The instant invention provides a process for encap-s!~lating oils and oil-soluble substances such as vitamins which overcomes the difficulties of rapid gelation, even in the pre-sence of filler materials, and which requires no large input of heat either to achieve discolution of the ingredients or to dehydrate the resulting microcapsules. The process accordingly provides a relatively inexpensive method of effectively encap-sulating oil~ and oil-soluble materia1s such that their resistance to oxidation is improved and their handling is-facili-tated.
In the proce6s an emulsion i6 formed which comprises a dispersed oil phase and a continuous phase of an alXali metal alginate and optionally a water-soluble, alcohol-in~oluble substance included as an alginate extender or filler.
Advantageously, no emulsifying agents need be employed since the alginate effectively serves this function. The emulsion is then formed into di~crete droplet~ and immersed in an alcoholic solu-tion of multivalent cations, typically calcium ions as calcium chloride, to convert the droplet6 to shape-retaining, substan-tially water-insoluble alginate gel micro-beads. If a filler is employed, it has been found that despite the presence of the forming alginate gel, it will be precipitated within the alginate matrix. Use of the alcohol based solution in this step, in addi-tion to 6erving as a precipitation agent for the filler, promotes dehydration of the forming microcapsules. The capsules may then ; be washed in fresh alcohol to remove salt~ and promote further drying. Lastly, the capsules are dried to remove residual alco-hol.
, 1The microcapsules thus produced comprise a mechanically stable composition of matter w~ich can be handled like a crystalline solid. The capsule wall comprises a matrix of water-insoluble multivalent cation-containing gel and a filler. Within the matrix is a plurality of compartments containing oil droplets shielded from atmospheric exposure.
In preferred embodiments, the filler material is a water-soluble, alcohol-insoluble polysaccharide æuch as dextran, the alcohol solution comprises a volatile alcohol such as methyl or ethyl alcohol, and the oil is an ingestible nutrient or con-~tains dissolved nutrient6 such a6 vitamins A, D, or E.
iAccordingly, objects of the invention include the pro-vision of a microencapsulation procedure effective to produce dry granule6 containing plural discrete droplets of an oleophilic substance completely ~urrounded by a protective alginate coating.
Another object iB to provide a stable, sub6tantially dry powder containing a dispersion of fat-soluble vitamin~, which powder is substantially insoluble in water but i8 readily ingested by mam-mals. Still another object i8 to provide encapsulation proce-dures which dispense with the use of gelatins. Another object is to provide a vitamin encapsulation procedure in which rapid gela-tion of the capsule matrix is effected without subjecting the ; capsules to a rapid temperature decrease. Yet another object is to provide a microencapsulation procedure wherein 601ution of the ingredients and drying of the product may be done with improved energy efficiency.
These and other objects and features of the invention be apparent from the following description and from the claims.
..
; -4-~,. .
!
1 ~cseription o~ a Preferred Embodiment In the process of the invention, an alkali metal algi-nate, typically sodium alginate, is di~solved in water at room te,mperatureS to produce a solution containing bet~een about one and four weight percent alginate. This solution is then diluted with a solution of a water-soluble, alcohol-insoluble filler or gel extender consisting of, for example, a 0-30~ aqueous ~olution of a polysaccharide such a~ dextran. Other suitable filler materials include sodium carboxy methyl cellulose, methyl cellu-lose, dextrins, and some soluble starches. Preferably, whendextran is used, a 20-30 ~eight percent solution is prepared.
The admixture of equal volumes of dextran and alginate solution results in a mixed ~olution consisting of between about 0.5 and 2.0 weight percent alginate and 0-15%, preferably 10-15% poly-saccharide. Out6tanding results have been obtained with between 0.8 and 1.2% ~odium alginate and 12% dextran.
Decreased concentrations of alginate in the 601ution below about 0.5% are increa&ingly ineffective in producing defect-free microcapsules. Increases of the alginate content above about 2%, while operable, result in a solution having a viscosity which ma~e droplet formation ai fficult. In general, the concentration of the alginate solution to be used should be increased as the amount of oil to be encapsulated is increased.
Next, the vitamin or other oil to be incorporated into the microcapsules is added to the aqueous solution typically on the order of 1%-10~ by weight (optimally 3%-6~). Among the fat-~oluble vitamin-active materials u~eful in the practice of the invention are vitamin bearing oils, pro vit~mins and pure or ` f ~
1 ~ubstantially ~u~e vitamins, both natural and synthetic, or chemical derivatives thereof, crude extractions containing such substances, and mixtures thereof. The invention ma~es possible the preparation of free-flowing powders containing, e.g., vitamin A, vitamin D, and vitamin E active materials as well as vitamin K, carotene and the like, or mixtures of such materials.
Preparations of this type are commercially available and typically include pharmaceutically acceptable anti-oxidants of the type well known to those 6killed in the art. The amount of oil used may range broadly between about 1.0~ and close to 30%.
However, at the higher end of the range, the 6tability of the oil-in-water emulsion is decreased and the quality of the micro-capsule is reduced.
The two-phase system is subjected to rapid stirring to induce emulsification of the oil phase in the aqueous phase.
Homogenizers, emulsifiers, or other high shear mixing apparatus are useful for this step. Ideally, the resulting emulsion con-tains oil droplets in the 1-3 micrometer range. Alginate in the continuous phase serves not only as a cap~ule wall forming material, but also as an emul6ifying agent. Accordingly, the emulsion will be found to be pressure stable and easily formed ` into 6ubstantially spherical droplets.
As ~oon as possible after formation of the emulsion, it i6 extruded from multiple orifices or otherwi~e formed into droplets of a ~ize preferably within the range of 300-1,000 micrometers. If de6ired, the droplet formation can be conducted under an inert gas blan~et. The droplets are then immediately collected, while ~ubstantially ~pherical, in a volatile .
. ; .
1 alcoholic, multiv~lent cation-containing ~olution, e.g., CaC12-As the droplets enter the alcoholic BolUtiOn, calcium ions are exc:hanged for the alkali metal of the alqinate, resulting in the formation of multiple ~alt bridges between alginate molecules and the creation of shape-retaining calcium alginate beadlets. Any dextran or other alcohol-insoluble polysaccharide is ~imultaneously precipitated within the alginate framework. This step results in essentially ins~antaneous gelation of the droplets, at room temperature, and in shrinkaqe of the droplets caused by dehydration.
Calcium ions, in a concentration of ~.0 - 2.5 weight percent, are the preferred multivalent cation for this step because of their low cost and low toxicity. Stronium or barium ions may also be used, but magnesium ions will not work. The preferred solvent is a low molecular weight alcohol such as methanol, or ethanol. Such low molecular weight alcohols are preferred because they subsequently can be removed easily from the microcapsule by volatilization. The filler in the microcap-6ule matrix serves to decrease oil migration within the capsules, reduce material co~ts and increase wall thickne6s. The alcohol - solution may be regenerated by distillation after use.
... .
As will be apparent from the foregoing, the alcohol solution ~erves three functions: First, it acts as a carrier for multivalent ions needed to contact and penetrate the liquid droplets in order to convert them from the liquid state to a ~hape-retaining, fiubstantially water-insoluble gel. Second, where, as preferred, fillers of the type ~escribed above are employed, it ~erves to precipitate the filler within the alginate v 1 ~1 matrix. Third, it promotes d~l~ydration o~ the microcapsules as water is dissolved in the alcohol.
Microcapsules collected from the solution will be found to contain residual calcium and sodium ions and the anions with which they are associated. These may conveniently be removed by one or more washing steps using salt-free, low molecular weight alcohol. Finally, residual alcohol and moisture is removed by drying the microcapsules, e.g., under vacuum or in air. The pro-duct of the foregoing procedure is a substanially dry, free-flowing, ~olid material comprising multiply compartmentalizedmicrocapsules having little or no tendancy to stick together and which contain multiple oil droplets completely encased ~y the microcapsule matrix. If a filler in the quantities set forth above as the preferred range is employed, the wall thickness of the capsule shields the vitamin or vitamins from making direct physical contact with the surrounding surface.
The invention will be further understood from the following non-limiting examples, wherein all percentages are given by weight.
Example 1 100 parts of a 2% sodium alginate (Sigma Chem. Co.) solution is thoroughly mix~d at room temperature with 100 parts of a 24% dextran (Sigma Chem. Co.) solution to produce a homoge-neous aqueous phase. Five parts vitamin A oil (commercial preparation) is then added to the solution and the two phase mix-ture is emulsified in a homogenizer (Tekmar) to form an oil-in-water emulsion wherein the oil droplets are generally within the ranse of 1-3 micrometers. The emulsion i8 fed through a 1 capillary disposed about one or a few inches above a 2.5% calcium chloride solution in methanol. The 8pherical emulsion droplets, upon entering the alcoholic solution, immediately gel to form substantially water and alcohol-in~oluble micro-beads contai~ing multiple droplets of the vitamin oil. A subsequent wash in methanol and vacuum drying at room temperature yield free-flowing pale yellow spherical micro-beads containing encapsulated vitamin A.
On examination under a microscope, the cross-section of the capsules exhibit a continuous and homogeneous multiply com-partmentalized capsule matrix completely enclo~ing plural oil droplets. Generally, each compartment in separate.
Example 2 The process of example 1 iB repeated except that 10 parts vitamin oil containing both vitamin A and vitamin D are employed in place of the vitamin A oil of Example 1, the beadlets are dehydrated and washed with isopropyl alcohol and the emulsion contains 10% sodium carboxy cellulose. This procedure results in microcapsules ~ubstantially identical to those of Example 1 but having an increased number of encapsulated oil droplets.
Exam~le 3 100 parts of the 2% sodium alginate ~olution of example 1 is admixed with 2 parts vegetable oil. After emulsification, droplets are formed and immersed in a 2.5~ CaC12 ~olution in methanol. The micro-beads are collected, washed twice in methanol, and vacuum dried. The resulting microcapsules comprise a plurality of vegetable oil droplets encased within a thin film of calcium alginate.
_g 1 As will be apparent from the foregoing Rpecification, the process of the invention is well suited for producing micro-capsu.les containing essentially any oil or oil-soluble substance including non-food substances. While this description is pri-marily directed to encapsulation of vitamins intended ultimately as an additive in foods, in view of the foregoing teachings, those skilled in the art will be able to substitute ingredients in place of those specifically disclosed herein when seeking to encapsulate other oi 18 or oil-soluble materials.
Other embodiments are within the following claims.
What is claimed is:
and 3,143,475. The vast majority of these and other vitamin encapsulating procedure6 involve the use of gelatins which are solidified about droplets of vitamin oil~ by rapidly lowering the temperature and subsequent dehydration.
While methods such as those disclosed in the patent literature set forth above have achieved ~ome 6ignificant com-mercial success, difficulties have sometimes been encountered inrapidly inducing solidification of the encapsulating material.
Furthermore, substantial quantities of heat are normally required in the course of gelatin-based proces~es in order to effectively dissolve the gelatin and to dehydrate the cap6ules produced.
I
, . , 1 Summary of the Invention The instant invention provides a process for encap-s!~lating oils and oil-soluble substances such as vitamins which overcomes the difficulties of rapid gelation, even in the pre-sence of filler materials, and which requires no large input of heat either to achieve discolution of the ingredients or to dehydrate the resulting microcapsules. The process accordingly provides a relatively inexpensive method of effectively encap-sulating oil~ and oil-soluble materia1s such that their resistance to oxidation is improved and their handling is-facili-tated.
In the proce6s an emulsion i6 formed which comprises a dispersed oil phase and a continuous phase of an alXali metal alginate and optionally a water-soluble, alcohol-in~oluble substance included as an alginate extender or filler.
Advantageously, no emulsifying agents need be employed since the alginate effectively serves this function. The emulsion is then formed into di~crete droplet~ and immersed in an alcoholic solu-tion of multivalent cations, typically calcium ions as calcium chloride, to convert the droplet6 to shape-retaining, substan-tially water-insoluble alginate gel micro-beads. If a filler is employed, it has been found that despite the presence of the forming alginate gel, it will be precipitated within the alginate matrix. Use of the alcohol based solution in this step, in addi-tion to 6erving as a precipitation agent for the filler, promotes dehydration of the forming microcapsules. The capsules may then ; be washed in fresh alcohol to remove salt~ and promote further drying. Lastly, the capsules are dried to remove residual alco-hol.
, 1The microcapsules thus produced comprise a mechanically stable composition of matter w~ich can be handled like a crystalline solid. The capsule wall comprises a matrix of water-insoluble multivalent cation-containing gel and a filler. Within the matrix is a plurality of compartments containing oil droplets shielded from atmospheric exposure.
In preferred embodiments, the filler material is a water-soluble, alcohol-insoluble polysaccharide æuch as dextran, the alcohol solution comprises a volatile alcohol such as methyl or ethyl alcohol, and the oil is an ingestible nutrient or con-~tains dissolved nutrient6 such a6 vitamins A, D, or E.
iAccordingly, objects of the invention include the pro-vision of a microencapsulation procedure effective to produce dry granule6 containing plural discrete droplets of an oleophilic substance completely ~urrounded by a protective alginate coating.
Another object iB to provide a stable, sub6tantially dry powder containing a dispersion of fat-soluble vitamin~, which powder is substantially insoluble in water but i8 readily ingested by mam-mals. Still another object i8 to provide encapsulation proce-dures which dispense with the use of gelatins. Another object is to provide a vitamin encapsulation procedure in which rapid gela-tion of the capsule matrix is effected without subjecting the ; capsules to a rapid temperature decrease. Yet another object is to provide a microencapsulation procedure wherein 601ution of the ingredients and drying of the product may be done with improved energy efficiency.
These and other objects and features of the invention be apparent from the following description and from the claims.
..
; -4-~,. .
!
1 ~cseription o~ a Preferred Embodiment In the process of the invention, an alkali metal algi-nate, typically sodium alginate, is di~solved in water at room te,mperatureS to produce a solution containing bet~een about one and four weight percent alginate. This solution is then diluted with a solution of a water-soluble, alcohol-insoluble filler or gel extender consisting of, for example, a 0-30~ aqueous ~olution of a polysaccharide such a~ dextran. Other suitable filler materials include sodium carboxy methyl cellulose, methyl cellu-lose, dextrins, and some soluble starches. Preferably, whendextran is used, a 20-30 ~eight percent solution is prepared.
The admixture of equal volumes of dextran and alginate solution results in a mixed ~olution consisting of between about 0.5 and 2.0 weight percent alginate and 0-15%, preferably 10-15% poly-saccharide. Out6tanding results have been obtained with between 0.8 and 1.2% ~odium alginate and 12% dextran.
Decreased concentrations of alginate in the 601ution below about 0.5% are increa&ingly ineffective in producing defect-free microcapsules. Increases of the alginate content above about 2%, while operable, result in a solution having a viscosity which ma~e droplet formation ai fficult. In general, the concentration of the alginate solution to be used should be increased as the amount of oil to be encapsulated is increased.
Next, the vitamin or other oil to be incorporated into the microcapsules is added to the aqueous solution typically on the order of 1%-10~ by weight (optimally 3%-6~). Among the fat-~oluble vitamin-active materials u~eful in the practice of the invention are vitamin bearing oils, pro vit~mins and pure or ` f ~
1 ~ubstantially ~u~e vitamins, both natural and synthetic, or chemical derivatives thereof, crude extractions containing such substances, and mixtures thereof. The invention ma~es possible the preparation of free-flowing powders containing, e.g., vitamin A, vitamin D, and vitamin E active materials as well as vitamin K, carotene and the like, or mixtures of such materials.
Preparations of this type are commercially available and typically include pharmaceutically acceptable anti-oxidants of the type well known to those 6killed in the art. The amount of oil used may range broadly between about 1.0~ and close to 30%.
However, at the higher end of the range, the 6tability of the oil-in-water emulsion is decreased and the quality of the micro-capsule is reduced.
The two-phase system is subjected to rapid stirring to induce emulsification of the oil phase in the aqueous phase.
Homogenizers, emulsifiers, or other high shear mixing apparatus are useful for this step. Ideally, the resulting emulsion con-tains oil droplets in the 1-3 micrometer range. Alginate in the continuous phase serves not only as a cap~ule wall forming material, but also as an emul6ifying agent. Accordingly, the emulsion will be found to be pressure stable and easily formed ` into 6ubstantially spherical droplets.
As ~oon as possible after formation of the emulsion, it i6 extruded from multiple orifices or otherwi~e formed into droplets of a ~ize preferably within the range of 300-1,000 micrometers. If de6ired, the droplet formation can be conducted under an inert gas blan~et. The droplets are then immediately collected, while ~ubstantially ~pherical, in a volatile .
. ; .
1 alcoholic, multiv~lent cation-containing ~olution, e.g., CaC12-As the droplets enter the alcoholic BolUtiOn, calcium ions are exc:hanged for the alkali metal of the alqinate, resulting in the formation of multiple ~alt bridges between alginate molecules and the creation of shape-retaining calcium alginate beadlets. Any dextran or other alcohol-insoluble polysaccharide is ~imultaneously precipitated within the alginate framework. This step results in essentially ins~antaneous gelation of the droplets, at room temperature, and in shrinkaqe of the droplets caused by dehydration.
Calcium ions, in a concentration of ~.0 - 2.5 weight percent, are the preferred multivalent cation for this step because of their low cost and low toxicity. Stronium or barium ions may also be used, but magnesium ions will not work. The preferred solvent is a low molecular weight alcohol such as methanol, or ethanol. Such low molecular weight alcohols are preferred because they subsequently can be removed easily from the microcapsule by volatilization. The filler in the microcap-6ule matrix serves to decrease oil migration within the capsules, reduce material co~ts and increase wall thickne6s. The alcohol - solution may be regenerated by distillation after use.
... .
As will be apparent from the foregoing, the alcohol solution ~erves three functions: First, it acts as a carrier for multivalent ions needed to contact and penetrate the liquid droplets in order to convert them from the liquid state to a ~hape-retaining, fiubstantially water-insoluble gel. Second, where, as preferred, fillers of the type ~escribed above are employed, it ~erves to precipitate the filler within the alginate v 1 ~1 matrix. Third, it promotes d~l~ydration o~ the microcapsules as water is dissolved in the alcohol.
Microcapsules collected from the solution will be found to contain residual calcium and sodium ions and the anions with which they are associated. These may conveniently be removed by one or more washing steps using salt-free, low molecular weight alcohol. Finally, residual alcohol and moisture is removed by drying the microcapsules, e.g., under vacuum or in air. The pro-duct of the foregoing procedure is a substanially dry, free-flowing, ~olid material comprising multiply compartmentalizedmicrocapsules having little or no tendancy to stick together and which contain multiple oil droplets completely encased ~y the microcapsule matrix. If a filler in the quantities set forth above as the preferred range is employed, the wall thickness of the capsule shields the vitamin or vitamins from making direct physical contact with the surrounding surface.
The invention will be further understood from the following non-limiting examples, wherein all percentages are given by weight.
Example 1 100 parts of a 2% sodium alginate (Sigma Chem. Co.) solution is thoroughly mix~d at room temperature with 100 parts of a 24% dextran (Sigma Chem. Co.) solution to produce a homoge-neous aqueous phase. Five parts vitamin A oil (commercial preparation) is then added to the solution and the two phase mix-ture is emulsified in a homogenizer (Tekmar) to form an oil-in-water emulsion wherein the oil droplets are generally within the ranse of 1-3 micrometers. The emulsion i8 fed through a 1 capillary disposed about one or a few inches above a 2.5% calcium chloride solution in methanol. The 8pherical emulsion droplets, upon entering the alcoholic solution, immediately gel to form substantially water and alcohol-in~oluble micro-beads contai~ing multiple droplets of the vitamin oil. A subsequent wash in methanol and vacuum drying at room temperature yield free-flowing pale yellow spherical micro-beads containing encapsulated vitamin A.
On examination under a microscope, the cross-section of the capsules exhibit a continuous and homogeneous multiply com-partmentalized capsule matrix completely enclo~ing plural oil droplets. Generally, each compartment in separate.
Example 2 The process of example 1 iB repeated except that 10 parts vitamin oil containing both vitamin A and vitamin D are employed in place of the vitamin A oil of Example 1, the beadlets are dehydrated and washed with isopropyl alcohol and the emulsion contains 10% sodium carboxy cellulose. This procedure results in microcapsules ~ubstantially identical to those of Example 1 but having an increased number of encapsulated oil droplets.
Exam~le 3 100 parts of the 2% sodium alginate ~olution of example 1 is admixed with 2 parts vegetable oil. After emulsification, droplets are formed and immersed in a 2.5~ CaC12 ~olution in methanol. The micro-beads are collected, washed twice in methanol, and vacuum dried. The resulting microcapsules comprise a plurality of vegetable oil droplets encased within a thin film of calcium alginate.
_g 1 As will be apparent from the foregoing Rpecification, the process of the invention is well suited for producing micro-capsu.les containing essentially any oil or oil-soluble substance including non-food substances. While this description is pri-marily directed to encapsulation of vitamins intended ultimately as an additive in foods, in view of the foregoing teachings, those skilled in the art will be able to substitute ingredients in place of those specifically disclosed herein when seeking to encapsulate other oi 18 or oil-soluble materials.
Other embodiments are within the following claims.
What is claimed is:
Claims (21)
1. A process for producing mechanically stable, multi-compartmentalized capsules containing an oil soluble nutrient, said process comprising the steps of:
A. forming an emulsion comprising a mixed aqueous solution of an alkali metal algi-nate and another non-toxic, water-soluble, alcohol-insoluble substance and a dispersed oil phase containing a nutrient:
B. forming discrete droplets of said emulsion;
C. immersing said droplets in an alcoholic solution of multivalent cations to convert said droplets to shape-retaining, water-insoluble alginate beads and to precipitate said alcohol-insoluble substance therewithin; and D. drying said beads.
A. forming an emulsion comprising a mixed aqueous solution of an alkali metal algi-nate and another non-toxic, water-soluble, alcohol-insoluble substance and a dispersed oil phase containing a nutrient:
B. forming discrete droplets of said emulsion;
C. immersing said droplets in an alcoholic solution of multivalent cations to convert said droplets to shape-retaining, water-insoluble alginate beads and to precipitate said alcohol-insoluble substance therewithin; and D. drying said beads.
2. The process of claim 1 wherein said alcohol-insoluble substance in dextran.
3. The process of claim 1 wherein, between steps C and D, said droplets are washed with alcohol to remove salts.
4. The process of claim 1 wherein said alcoholic solu-tion comprises calcium ions dissolved in methanol.
5. The process of claim 1 wherein said alcoholic solu-tion comprises an alcohol selected from the group consisting of methyl and ethyl alcohol and mixtures thereof.
6. me process of claim 1 wherein said alcohol-insoluble substance is a polysaccharide.
//
//
7. The process of claim 1 wherein said nutrient comprises an oil-soluble vitamin.
8. The process of claim 1 wherein said nutrient is selected from the group consisting of vitamin A, vitamin D, vita-min E, and mixtures thereof.
9. The process of claim 1 wherein the alkali metal alginate is sodium alginate.
10. A process for producing mechanically stable, multi-compartmentalized capsules containing at least one oil-soluble vitamin, said process comprising the steps of:
A. forming an emulsion comprising a continous phase comprising a mixed aqueous solu-tion of sodium alginate and dextran and a dispersed oil phase containing a vitamin:
B. forming discrete droplets of said emulsion;
C. immersing said droplets in an alcoholic solution of calcium ions to convert said droplets to shape-retaining alginate beads and to precipitate the dextran therewithin; and D. drying the beads.
A. forming an emulsion comprising a continous phase comprising a mixed aqueous solu-tion of sodium alginate and dextran and a dispersed oil phase containing a vitamin:
B. forming discrete droplets of said emulsion;
C. immersing said droplets in an alcoholic solution of calcium ions to convert said droplets to shape-retaining alginate beads and to precipitate the dextran therewithin; and D. drying the beads.
11. The process of claim 10 wherein, between steps C
and D, said droplets are washed with alcohol to remove sodium and calcium ions.
and D, said droplets are washed with alcohol to remove sodium and calcium ions.
12. The process of claim 10 wherein said alcoholic solution comprises methanol.
13. A process for encapsulating an oleophilic substance within a mechanically stable, multi-compartmentalized substantially water-insoluble matrix, said process comprising the steps of:
A. forming an emulsion comprising a continuous phase of an aqueous solution of alkali metal alginate another water soluble, alcohol insoluble material comprising a filler and a dispersed oil phase;
B. forming discrete droplets of said emulsion;
C. immersing said droplets in an alcoholic solution of multivalent cations to convert said droplets to shape-retaining alginate beads and to precipitate said filler within the shape retaining alginate beads; and D. drying said beads.
A. forming an emulsion comprising a continuous phase of an aqueous solution of alkali metal alginate another water soluble, alcohol insoluble material comprising a filler and a dispersed oil phase;
B. forming discrete droplets of said emulsion;
C. immersing said droplets in an alcoholic solution of multivalent cations to convert said droplets to shape-retaining alginate beads and to precipitate said filler within the shape retaining alginate beads; and D. drying said beads.
14. The process of claim 13 wherein the alginate is sodium alginate and the alcoholic solution comprises a methanol-calcium chloride solution.
15. The process of claim 13 wherein, between steps C
and D, said beads are washed to remove salts.
and D, said beads are washed to remove salts.
16. The process of claim 13 wherein said filler comprises a polysaccharide.
17. The process of claim 16 wherein said polysaccharide comprises dextran.
18. A composition of matter comprising a mechanically stable matrix consisting essentially of a water-insoluble multivalent cation containing alginate structure and another water-soluble alcohol-insoluble polysaccharide, said matrix defining a plurality of compartments containing an oleophilic material.
19. The composition of claim 18 wherein said alginate structure comprises calcium alginate.
20. The composition of claim 18 wherein said polysaccharide comprises dextran.
21. The composition of claim 18 wherein said oil soluble substance is a vitamin.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/205,340 US4389419A (en) | 1980-11-10 | 1980-11-10 | Vitamin encapsulation |
| US205,340 | 1980-11-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1164800A true CA1164800A (en) | 1984-04-03 |
Family
ID=22761797
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000389651A Expired CA1164800A (en) | 1980-11-10 | 1981-11-06 | Vitamin encapsulation |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US4389419A (en) |
| JP (1) | JPS57150613A (en) |
| CA (1) | CA1164800A (en) |
| DE (1) | DE3144683A1 (en) |
| FR (1) | FR2493701B1 (en) |
| GB (1) | GB2086835B (en) |
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| JPS557241A (en) * | 1978-06-30 | 1980-01-19 | Nippon Carbide Ind Co Ltd | Artificial granules and their preparation |
-
1980
- 1980-11-10 US US06/205,340 patent/US4389419A/en not_active Expired - Lifetime
-
1981
- 1981-11-06 CA CA000389651A patent/CA1164800A/en not_active Expired
- 1981-11-09 FR FR8120957A patent/FR2493701B1/en not_active Expired
- 1981-11-10 JP JP56179111A patent/JPS57150613A/en active Granted
- 1981-11-10 GB GB8133857A patent/GB2086835B/en not_active Expired
- 1981-11-10 DE DE19813144683 patent/DE3144683A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57150613A (en) | 1982-09-17 |
| DE3144683A1 (en) | 1982-06-24 |
| JPS6250446B2 (en) | 1987-10-24 |
| GB2086835B (en) | 1984-04-18 |
| US4389419A (en) | 1983-06-21 |
| GB2086835A (en) | 1982-05-19 |
| FR2493701B1 (en) | 1986-11-14 |
| FR2493701A1 (en) | 1982-05-14 |
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