MXPA97009198A - Methods and compositions for preparing soft degelatine capsules that have resistant coverings to permeation by rell materials - Google Patents

Abstract

The present invention discloses gelatin capsules having a means for isolating the filling material from the gelatin material forming the capsule shell.

Description

METHODS AND COMPOSITIONS FOR PREPARING SOFT GELATINE CAPSULES THAT HAVE COVERINGS RESISTANT TO PERMEATION BY BACKGROUND MATERIALS BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to the field of gelatine capsules containing a filler material comprising a liquid phase. More specifically, this invention relates to gelatin capsules comprising a gelatin shell turned impervious to migration of the filling material to the gelatin shell. Description of the Related Art Soft gels or soft gelatin capsules are predominantly used to contain liquids, wherein the active ingredients are present in the dissolved or suspended state. The liquids used as a portion of the fillers commonly include vegetable oils, animal oils, mineral oils, liquid hydrocarbons, essential oils, polyethylene glycol. Fats and waxes are also commonly used or added to the filling to modify its consistency. In addition, the filling material of the soft gelatin capsule REF: 26206 can contain at most about 8% water by weight. However, certain liquid materials do not match and / or interact with the gelatin that forms the capsule shell. This migration or interaction has a deleterious effect on the stability and structure of the gelatin capsule. For example, water, a solvent for the proteinaceous material that forms the gelatin, dissolves the ge. atina. Thus, the filling materials for gelatin capsules can only be prepared to include a liquid phase comprising at most about 8% water by weight. Similar problems are found using other liquids in filling materials for gelatin capsules. Polyethylene glycol, ethanol, propylene glycol, and similar polar low molecular weight solvents also interact adversely with the gelatin shell. These problems are described in U.S. Patents 4,888,239 and 4,780,316. It is noted that the problems associated with these liquids are not only associated with the migration of the liquid to the cover. Certain liquids, for example polyethylene glycol, are hygroscopic and tend to absorb plasticizers from the roofing material, causing the roof to become brittle.

Accordingly, there is a need to prepare gelatin capsules which will be substantially resistant to migration of the liquid materials from the filling to the gelatin capsule, thereby causing the gelatin capsule to have a predetermined stability. Additionally, there is a need to prevent migration of the shell components to the fill material. BRIEF DESCRIPTION OF THE INVENTION The invention includes gelatin capsules having a barrier that effectively insulates the gelatin shell and its filler components. Thus, the invention provides gelatin capsules comprising a multi-layer cover, having an outer layer and at least one inner layer, which acts as a barrier. The filler material, which comprises a hydrophilic or hydrophobic component, is disposed within the multi-layer cover. The outer layer of the gelatin capsule typically comprises gelatin, while the barrier (in certain cases the layer that is in contact with the filling) is formed of a material resistant to migration of the hydrophilic or hydrophobic components of the filling material to the outer layer. A variety of combinations of the outer layer of gelatin adhered to other layers, including the barrier, is included within the scope of the invention. Thus, the invention provides gelatin capsules capable of containing a filling material comprising more than 8% by weight of water. The resulting gelatin capsules comprising water have excellent long-term stability, and are capable of encapsulating a variety of liquid landing materials. The invention further includes gelatin capsules capable of containing a filler material having a tendency to absorb water or other shell materials, without any of the shell components being absorbed by the filler. The resulting gelatin capsules can be prepared to include a variety of solutions, lotions, emulsions, creams, gels or suspensions. The invention further provides gelatin capsules capable of encapsulating within the filler a variety of components that can adversely affect the physical or chemical stability of the gelatin capsule shell. Thus, the filling material can include pharmaceutical compounds such as synthetic drugs and proteins, various antibodies and enzymes, and vitamins and minerals, very pure chemicals, industrial chemicals, solvents, insecticides, etc. The invention further provides a method for manufacturing gelatin capsules, wherein the gelatin capsules are capable of containing a liquid filler material that is also capable of interacting adversely with the gelatin shell. The method comprises forming a gelatin strip, the gelatin strip has an outer layer comprising gelatin, and an outer layer resistant to migration of hydrophilic and hydrophobic materials; preparing a filling material comprising a system comprising a liquid that can interact adversely with gelatin; and encapsulating the filling material within the gelatin strip, using a rotating nozzle encapsulation apparatus. The invention also provides composite films comprising a gelatin layer and a barrier layer, wherein the barrier layer is resistant or impermeable to migration of the hydrophilic and hydrophobic materials through the barrier. Composite films, ie, multilayer gelatin strips, prepared according to the invention to have a gelatin layer and at least one barrier layer can also be used as wrapping sheets, or a variety of articles. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a cross-sectional diagram of a nozzle having a cavity-support configuration of a groove, showing the opening 2 and the edge 1 of the nozzle; Figure 2 is a cross-sectional diagram of a coextrusion nozzle with feed block, showing the openings 4, 4a and 4b, and the outlet opening 3: Figure 3 is a cross-sectional diagram of a slot nozzle multiple and multiple outputs, showing the openings 5, 5a and 5b, and the edge of the nozzle 6; and Figures 4 and 5 are cross section diagrams of nozzles with multiple nozzles and one outlet, showing the openings 7, 7a, and 7b, and the edge 8 of the nozzle. DETAILED DESCRIPTION OF THE INVENTION The gelatin capsules of the invention comprise a cover and a filling material disposed within the cover. The cover comprises at least one outer layer and at least one inner layer, which functions as a barrier layer. The outer layer typically comprises gelatin, while the barrier layer is formed of a material that is resistant to permeation by the materials forming the filling material. Thus, the cover includes a barrier layer as an inner layer which prevents migration of the liquid material from the filling to the outer layer of gelatin. The barrier layer may be adjacent to the filler material, and in contact with the filler material, or may be isolated from the filler material by an interlayer of gelatin or other material. Additionally, the barrier layer may comprise a plurality of layers of impervious or permeation resistant material by the filler material. The filler material comprises any of a variety of liquid components, in addition to various solid materials. The liquid may be a hydrophilic liquid, or it may be a hydrophobic, ie, lipophilic liquid. Representative hydrophilic components include water, alcohols of 1 to 3 carbon atoms, polyethylene glycols, glycerol, propylene glycol, acids of 1 to 4 carbon atoms, glycerides of 8 to 10 carbon atoms polyglycolylated saturated, glyofural, monoethyl ether of diethylene glycol, high fructose corn syrup, maltose syrup, maltitol syrup, glucose syrup, sugar syrup, honey, and sorbitol. Representative hydrophobic or lipophilic components include hydrocarbons such as, for example, mineral oils, petrolatum, polyethylene waxes, and microcrystalline waxes, synthetic esters such as, for example, isopropyl myristate; natural esters such as, for example, vegetable oils, animal fats and lanolin; natural alcohols of large chain; large chain synthetic alcohols; natural fatty acids of large chain; large chain synthetic fatty acids; ethers such as, for example, polyoxypropylenes; silicones such as, for example, substituted or unsubstituted silicones; mixed plant waxes such as candelilla; mixed animal waxes such as beeswax; or mixtures of any of these components. As noted above, the cover comprises an outer layer and at least one barrier layer, which may be the inner layer in contact with the filling material of the capsule. These layers are discrete layers, which are preferably mixed in their interfacial zone, to improve the adhesion between the layers. The invention includes a variety of combinations of an outer layer of gelatin and inner layers, wherein at least one inner layer is a barrier layer. The other inner layers may be formed of gelatin or other suitable material, such as, for example, agar, pectin, alginate, starch, carrageenan, cellulose or similar polysaccharides or other film-forming polymer, such as, for example, lacquer or whey protein The cover of the capsule is a composite material of multiple layers of an outer layer and at least one inner layer. The composite material can be a two-layer, three-layer, or four-layer cover. Optionally, the cover can be a multi-layer composite having more than four layers. The particular properties of the desired final product can be altered using such combinations. Examples of these alternative combinations are as follows: Outer layer Inner layers Gelatin barrier gelatin barrier: barrier gelatin barrier: gelatin gelatin gelatin: gelatin barrier barrier: gelatin: gelatin barrier barrier: agar: gelatin barrier agar: gelatin: barrier strips Multiple layers for use in the invention are from 0.254 mm to 1.78 mm (0.01 to 0.07 inches), preferably from about 0.508 mm to 1.27 mm (0.02 to 0.05 inches), and more preferably from about 0.762 mm to 0.89 mm ( 0.03 to 0.035 inches) thick. The layer that is in contact with the filling material may be a layer of gelatin, optionally modified as described below, to protect and isolate the barrier layer during the manufacture of the strip and the final gelatin capsule. This gelatin layer can be a protective or lubricating layer, which insulates the adherent barrier of the encapsulation apparatus. The outer layer comprises gelatin and a plasticizer for gelatin. The gelatin dough used to prepare the capsule shell is made according to conventional methods, using traditional components. The gelatin may optionally include a composition that inhibits embrittlement, which comprises materials such as a mixture of sorbitol and one or more sorbitans. See U.S. Patent No. 4,780,316. Additionally, the gelatin may optionally include an agent that provides adhesion or a viscosity modifier. Examples of tackifying agents and viscosity modifiers are the ethylene-acrylic acid copolymer and the amylose copolymer, respectively. A preferred outer layer of gelatin comprises gelatin, glycerin as a plasticizer, and water. In preferred embodiments of a dried finished capsule according to the invention, the gelatin present in the outer layer is about 40-70% by weight of the outer layer; glycerin is from about 20-40% by weight of the outer layer; and the water is about 5-15% by weight of the outer layer. When the layer that is in contact with the filling material is a gelatin layer, that gelatin layer can optionally be modified by the addition of hydrophobic components. Suitable representative hydrophobic components include colloidal silicas, modified silicas, silicones, modified silicones, magnesium stearate, oxidized polyethylene homopolymer, polyethylene homopolymer, paraffin wax, or mixtures of these materials. The barrier layer of the cover comprises any of a variety of homopolymers or copolymers. Such polymers can be derived from the polymerization of a monomer of the group consisting of acrylamide, acrylic acid, acrylonitrile, caprolactones, ethylene, furan, maleic anhydride, methacrylate, methacrylic acid, methacrylate, ethylpropylene, styrene, vinyl acetate, vinyl alcohol, vinyl chloride, ethyl vinyl ether, vinyl propyl ether, vinyl pyrrolidone, salts of any of the acids mentioned above, or mixtures of these materials. The inner layer may also comprise a paraffin wax. The barrier layer may additionally comprise hydrocarbons such as polyethylene waxes or microcrystalline waxes, synthetic esters such as isopropyl myristate, natural esters such as vegetable oils, animal fats, or lanolin, natural large chain alcohols, large chain synthetic alcohols, natural fatty acids of large chain, synthetic fatty acids of large chain, ethers such as for example polyoxypropylenes, silicones, mixed plant waxes, mixed animal waxes such as beeswax, or mixtures thereof. A solid mixture of hydrocarbons having from 18 to 36 carbon atoms is proposed by microcrystalline wax. Such solid hydrocarbons have molecular weights from about 49 to 800, and viscosities from about 45 to 120 Saybolt Universal Seconds (SUS) at 99 ° C (210 ° F). Preferred inner layers of the shell comprise paraffin waxes, polyethylene homopolymers or polyethylene copolymers. A particularly preferred inner layer comprises ethylene-acrylic acid copolymer available from Allied Signal, Inc., Morristown, N.J. and microcrystalline wax available from Witco Corporation, Greenwich, CT. In the particularly preferred inner layers of the capsules of the invention, the ethylene-acrylic acid copoiimer is from about 50-90% by weight of the inner layer, and a microcrystalline wax is about 10-50% by weight of the inner layer. Other preferred interior layers have the following compositions: Barrier Layer Composition Component Provider% P / P Components Ethylene Copolymer - Acrylic Acid, A-C5180 70 Allied Signal, Inc. Microcrystalline Wax 30 Witco Corp .; or Petrolite Corp.

The cover is formed in such a way that each layer adheres securely to the other layer. For example, in a two-layer shell of the capsule, the gelatin layer, i.e. the outer layer, adheres to the inner layer, i.e., the barrier layer.

The cover according to the invention is prepared from a multi-layer strip, for example, two-layer, or three-layer, comprising materials that allow its processing in a soft gelatin capsule on a nozzle encapsulation machine rotating, without delamination or separation of the various layers of the multi-layer strip. Satisfactory adhesion is defined as adhesion between layers sufficient to prevent separation or delamination during all stages of the encapsulation process. The material of the barrier layer is selected such that it is impermeable to hydrophilic materials such as for example water, polyethylene glycols, glycerol, propylene glycol, various alcohols of 1 to 3 carbon atoms, etc. The barrier layer must also be impermeable to a variety of hydrophobic or lipophilic vehicles, such as fractionated coconut oil, light mineral oil, petroleum jelly, etc. The materials that form the cover must act as a single uniform strip of cover material, that is, the materials must have properties similar to those of a typical strip of gelatin. Each inner layer, including the barrier layer, when adhered to the outer layer, must have sufficient elasticity, strength and heat sealing capabilities to allow processing of the multilayer material in a capsule on a rotating nozzle encapsulation machine . The adhesion of each layer to another layer, for example, the barrier layer to the gelatin layer, can be improved by incorporating agents that provide adhesion to the formulations of the gelatin mass, or the inner layer or the barrier layer, or each layer material; alternatively, it can be improved by physically modifying the layers during the manufacturing process. Examples of tackifying agents and viscosity modifiers include the ethylene-acrylic acid and amylose copolymer, respectively. To obtain the suitable material for preparing a multi-layered cover of gelatin and at least one barrier material, either the gelatin mass or the barrier material can be modified by the addition of viscosity modifiers in any of the gelatin mass. or the filling formulation of the barrier. Alternatively, the rheological characteristics of these materials can be modified by physically changing the manufacturing process. There are a variety of methods for preparing a multi-layer strip suitable for use in the preparation of gelatin capsules. The apparatus for preparing the gelatin capsules of the invention is rotary nozzle encapsulation machine modified in such a way that the inner and outer layers of the capsule shell are simultaneously formed by co-extrusion on a molding cylinder, using a feed block for coextrusion and a single nozzle intercalation nozzle, and one outlet. Preferred embodiments include machines modified in such a way that the inner and outer layers are co-extruded onto a molding cylinder, using a multiple nozzle interleaving nozzle and multiple outlets. Another alternative includes preparing the inner and outer layers sequentially, by extrusion on a molding cylinder, using a multiple nozzle cladding-support slot nozzle and a single outlet. Typically, the gelatin strip is formed by simultaneously coextruding the inner and outer layers onto a molding cylinder.Extrusion nozzles suitable for preparing the multi-layer films of the invention are typically capable of (1) forcing molten gelatin and the barrier materials in thin films, (2) keep the molten materials at a constant temperature; and (3) dosing the molten materials at a constant pressure and velocity to the nozzle conductive reservoir, to prepare a film of uniform width. Examples of extrusion nozzles suitable for use in the invention include those listed in the following table: Nozzle Type Extrusion Manufacturer Extrusion Nozzle Single Extrusion Dies, Inc. Chippewa One Exit (Falls Configuration, Wl Coating Nozzle Killion Extruders, Inc., Cedar -Sort Grove, NJ Liberty Tool Corp., Rochester, NY Multiple Extrusion Nozzles Dies, Inc., Chippewa One Output Falls, Wl Multiple Nozzles Liberty Tool Corp., Rochester, Multiple Outlets NY Power Block _ Randcastle Extrusion Systems, Coextrusion Nozzle Inc., Cedar Grove, NJ The Cloeren Company, TX In a coextrusion feedblock system, a coextrusion feedblock such as the one shown in Figure 2 is mounted on a liner-support type nozzle such as the one shown in Figure 1, in such a way that the outlet opening 3 is adjacent to the feed opening 2. The coextrusion feed block and the nozzle are mounted adjacent to a molding cylinder, to supply the cylinder with a film of material. In the nozzles shown in Figures 1, 3, 4 and 5, the openings provide the edge of the nozzle with the material of one layer, two layers, or multiple layers, depending on the configuration. The nozzle is mounted on a rotary nozzle encapsulation apparatus, such that the edges of the nozzle are adjacent to the molding cylinder, and provide the molding roll with a thin film of material. Other methods that can be exploited to prepare a multi-layer strip include: (1) spray coating uniform layers of coating material onto a substrate layer; (2) laminating a preformed layer on a substrate layer; and (3) applying a coating layer on a substrate, using a transfer roller system.

The following examples are included to illustrate the practice of this invention.

E.TEMPLO 1 Two-layer soft gelatin capsules were fabricated on a rotary nozzle encapsulation apparatus, using the materials shown below, in Table 1. The two-layer (gelatin-barrier) strips were formed by a coextrusion technique . This two-layer strip was formed by a multi-nozzle manifold and multiple outlets. TABLE 1 Composition of the Soft Two-Capsule Capsule Cover Capsule Coating Dry Cover Composition Soft Ingredient%. P / P Outer Layer Gelatin, NF (150 43 Bloom) Glycerin, USP 20 Purified Water, 8 USP Inner Layer: Ethylene Copolymer-20 Acrylic Acid (A-C5180) Microcrystalline Wax Formulation 1: A solution of PEG 400 containing 20% w / w of water was encapsulated in the two-layer capsule with the coating composition described in Table I. Soft gelatin capsules with good joints were obtained. Formulation 2: A PEG solution containing 40% w / w of water was encapsulated in the two-layer capsule with the coating composition described in Table I. Soft gelatin capsules with good seals were obtained. Formulation 3: A two-layer capsule was prepared with the coating composition described in Table I, which contained 100% purified water as a filler. Soft gelatine capsules with good joints were obtained. Formulation 4: A two-layer capsule was prepared with the coating composition described in Table I, which contained as a filler a water-in-oil ointment, comprising about 25% water by weight. Soft gelatine capsules were obtained with good joints, using a rotating nozzle encapsulation apparatus.

Formulation 5: A hydro-alcoholic solution containing 35% w / w of water, 5% w / w of propylene glycol and 60% alcohol was encapsulated in a two-layer capsule having the coating composition described in Table 1 We obtained soft gelatin capsules with good joints. Formulation 6: An oil-in-water emulsion cream containing 68% w / w water, 6% w / w cetearyl alcohol, 6% cetyl ester wax, 2.5% w / w sorbitan monostearate, 2.5% w / w of polysorbate 60, 13% w / w of octyl dodecanol, and 2% w / w of benzyl alcohol was encapsulated in a two-layer capsule having the coating composition described in Table 1. Soft gelatin capsules with good joints. Formulation 7: a water-in-oil emulsion, containing 56.3% w / w water, 10% w / w POE glycerol sorbitan isostearate, 3% beeswax, 3% w / w lanolin, % w / w of caprylic / capric triglyceride, 11% w / w of squalene, 3% w / w of sunflower oil, 2% w / w of glycerin, and 0.7% w / w of magnesium sulfate were encapsulated in a Two layer capsule having the coating composition described in Table 1. Soft gelatine capsules with good joints were obtained. Formulation 8: A clear emollient gel, containing 58% w / w of ethanol, 1% w / w of hydroxypropyl cellulose, and 41% w / w of ethoxy-diglycol encapsulated in a two-layer capsule having the coating composition described in Table 1. Soft gelatine capsules with good joints were obtained. EXAMPLE 2 Composite two-layer and gelatin-barrier strips were prepared, comprising a barrier layer containing a 70:30 mixture of ethylene-acrylic acid copolymer and microcrystalline wax, wherein the gelatin and barrier layers had thicknesses of 0.483 mm and 0.838 mm (0.019 and 0.033 inches), respectively. For comparison purposes, a 0.813 mm (0.032 mm) thick gelatin layer was prepared using conventional gelatin strip molding methods. The steam permeation rates for each strip are shown in Tables II and III below. TABLE 2 Steam Permeation of Water through the Two Layer Strip at 23% Relative Humidity and 25 ° C Time (Hours) Water Loss (% w / w / cm2) 41 0.291 48 0.311 120 0.394 216 0.423 360 0.476 456 0.493 1488 0.502 TABLE III Permeation of Water Vapor through the Gelatine Strip at 23% Relative Humidity and 25 ° C Time (Hours) Water Loss (% p / p / cm2) 43 14 96 33 168 87 336 100 Many other modalities that are not specifically described or discussed above may nevertheless fall within the spirit and scope of the present invention and claims.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Having described the invention as above, property is claimed as contained in the following:

Claims (29)

1. CLAIMS 1. A soft gelatin capsule made by the rotating nozzle process, the capsule is characterized in that it comprises: (a) a cover having at least one outer layer and [a] at least one barrier layer; and (b) a pumpable filler material, disposed within the cover, the barrier layer is disposed between the outer layer and the filler material; the filler comprises a hydrophilic component, a hydrophobic component, an amphiphilic component, or mixtures thereof; the outer layer comprises gelatin, and the barrier layer is resistant to migration of the hydrophilic, amphiphilic, and hydrophobic components of the filler material to the outer layer.
2. 2. A gelatin capsule according to claim 1, characterized in that the barrier layer is adhered to the outer layer.
3. 3. A gelatin capsule according to claim 1, characterized in that the hydrophilic component is water, or alcohols of 1 to 3 carbon atoms, polyethylene glycol, glycerol, or propylene glycol.
4. 4. A gelatin capsule according to claim 1, characterized in that the hydrophobic component is an oil.
5. 5. A gelatin capsule according to claim 1, characterized in that the barrier layer comprises: a paraffin wax, a polyethylene homopolymer, a polyethylene copolymer, a polymer derived from the polymerization of a monomer selected from the group consisting of of acrylamide, acrylic acid, acrylonitrile, caprolactones, ethylene, furan, maleic anhydride, methacrylate, methacrylic acid, methacrylate, methylpropylene, styrene, vinyl acetate, vinyl alcohol, vinyl chloride, ethyl vinyl ether, vinylpropyl ether, vinyl pyrrolidone, salts or mixtures thereof, a hydrocarbon, a polyethylene wax, a microcrystalline wax, a synthetic ester, a natural ester, a natural large chain alcohol, a synthetic large chain alcohol, a natural large chain fatty acid, a fatty acid synthetic large chain, an ether, or mixtures thereof.
6. 6. A gelatin capsule according to claim 1, characterized in that the outer layer comprises gelatin modified with an agent that provides adhesion.
7. 7. A gelatin capsule according to claim 1, characterized in that the barrier layer comprises an agent that provides adhesion.
8. 8. A gelatin capsule according to claim 6, characterized in that the outer layer further comprises a viscosity modifier.
9. 9. A gelatin capsule according to claim 7, characterized in that the barrier layer additionally comprises a viscosity modifier.
10. 10. A gelatin capsule according to claim 1, characterized in that the barrier layer comprises ethylene-acrylic acid copolymer and microcrystalline wax.
11. 11. A gelatin capsule according to claim 1, characterized in that the filling material comprises a solvent system comprising up to about 100% water.
12. 12. A method for manufacturing a gelatin capsule capable of containing a filler material comprising up to about 100% water, the method is characterized in that it comprises: (a) forming a gelatin strip, the gelatin strip has a layer exterior comprising gelatin, and a barrier layer resistant to migration of hydrophilic or hydrophobic materials; (b) preparing a filler material to comprise a solvent system comprising up to about 100% water by weight of the solvent system; and (c) encapsulating the filling material within the gelatin strip, using a rotating nozzle encapsulation apparatus.
13. 13. A method according to claim 12, characterized in that the formation of a gelatin strip simultaneously comprises coextruding the barrier layer and the outer layer onto a molding cylinder.
14. 14. A method according to claim 13, characterized in that the barrier layer and the outer layer are co-extruded onto the molding cylinder using a multi-outlet multi-nozzle intercalation nozzle.
15. 15. A method according to claim 12, characterized in that the outer layer comprises gelatin and an agent that provides adhesion.
16. 16. A method according to claim 12, characterized in that the barrier layer comprises a paraffin wax, a polyethylene homopolymer, a polyethylene copolymer, a polymer derived from the polymerization of a monomer selected from the group consisting of acrylamide, acrylic acid, acrylonitrile, caprolactones, ethylene, furan, maleic anhydride, methacrylate, methacrylic acid, methacrylate, methylpropylene, styrene, vinyl acetate, vinyl alcohol, vinyl chloride, ethyl vinyl ether, vinylpropyl ether, vinyl pyrrolidone, salts or mixtures thereof same, a hydrocarbon, a polyethylene wax, a microcrystalline wax, a synthetic ester, a natural ester, a natural large chain alcohol, a synthetic large chain alcohol, a large chain natural fatty acid, a synthetic chain fatty acid large, an ether, or mixtures thereof.
17. 17. A soft gelatin capsule, made by the rotating nozzle process, the capsule is characterized in that it comprises: (a) a cover comprising an outer layer and a water retention means; and (b) a pumpable packing material, encapsulated within the shell, the filling material comprises up to about 100% water by weight of the filling material, the water holding means is disposed between the outer layer and the filling material.
18. 18. A gelatin capsule according to claim 17, characterized in that the water retention means comprises a barrier layer disposed within an outer layer of gelatin.
19. 19. A soft gelatin capsule, made by the rotating nozzle process, the capsule is characterized in that it comprises: (a) a cover comprising a water retention means; and (b) a pumpable filler material, encapsulated by the shell, the filler material comprises a solvent system comprising up to about 100% water by weight of the solvent system.
20. 20. A method for preventing the migration of materials from a filling material disposed within a gelatin capsule to the gelatin layer of the gelatin capsule, the method is characterized in that it comprises making a capsule shell comprising a layer of gelatin. isolated from the filling material by a barrier layer.
21. 21. A composite film, characterized in that it comprises a gelatin layer and a barrier layer resistant to the permeation of hydrophobic and hydrophilic materials.
22. 22. A composite film according to claim 21, characterized in that the barrier layer is resistant to water permeation.
23. 23. A soft gelatin capsule, made by the rotating nozzle process, the capsule is characterized in that it comprises: (a) a multi-layer cover, having an outer layer and a plurality of inner layers, wherein at least one layer interior is a barrier layer; and (b) a pumpable filler material disposed within the shell, the filler comprises a hydrophilic component, a hydrophobic component, an amphiphilic component, or mixtures thereof; the barrier layer is disposed between the outer layer and the filling material; the outer layer comprises gelatin, and the barrier layer is resistant to migration of the hydrophilic, amphiphilic, and hydrophobic components of the filler material to the outer layer.
24. 24. A soft gelatin capsule, made by the rotating nozzle process, the capsule is characterized in that it comprises: (a) a two-layer cover, having an outer layer and a barrier layer; and (b) a pumpable filler material disposed within the shell, the filler comprises a hydrophilic component, a hydrophobic component, an amphiphilic component, or mixtures thereof; the barrier layer is disposed between the outer layer and the filling material; the outer layer comprises gelatin, and the barrier layer is resistant to migration of the hydrophilic, amphiphilic, and hydrophobic components of the filler material to the outer layer.
25. 25. A soft gelatin capsule, made by the rotating nozzle process, the capsule is characterized in that it comprises: (a) a three-layer cover, having an outer layer and two inner layers, wherein at least one inner layer is a barrier layer; and (b) a pumpable filler material disposed within the shell, the filler comprises a hydrophilic component, a hydrophobic component, an amphiphilic component, or mixtures thereof; the outer layer comprises gelatin, and the barrier layer is resistant to migration of the hydrophilic, amphiphilic, and hydrophobic components of the filler material to the outer layer.
26. 26. A soft gelatin capsule, made by the rotating nozzle process, the capsule is characterized in that it comprises: (a) a cover having at least one outer layer and at least one barrier layer; and (b) a pumpable filler material disposed within the shell, the filler comprises a hydrophilic component, a hydrophobic component, an amphiphilic component, or mixtures thereof; the barrier layer is disposed between the outer layer and the filling material; the outer layer comprises gelatin, and the barrier layer is resistant to the migration of the shell components of the outer layer to the filling material.
27. 27. A soft gelatin capsule, made by the rotating nozzle process, the capsule is characterized in that it comprises: (a) a cover consisting of an outer layer, an inner layer, and a barrier layer disposed between the outer layer and the interior, where the outer and inner layers are layers of gelatin; and (b) a pumpable filler material disposed within the shell, the filler comprises a hydrophilic component, a hydrophobic component, an amphiphilic component, or mixtures thereof; the barrier layer is resistant to migration of the hydrophilic, amphiphilic, and hydrophobic components of the filler material to the outer layer.
28. 28. A soft gelatin capsule, the capsule is characterized in that it comprises: (a) a cover having a seal and at least one outer layer and at least one barrier layer; and (b) a pumpable filler material disposed within the shell, the filler comprises a hydrophilic component, a hydrophobic component, an amphiphilic component, or mixtures thereof; the barrier layer is disposed between the outer layer and the filling material; the outer layer comprises gelatin, and the barrier layer is resistant to the migration of the shell components of the outer layer to the filling material.
29. 29. A soft gelatin capsule, made by the rotating nozzle process, the capsule is characterized in that it comprises: (a) a cover having a seal and consisting of an outer layer, an inner layer, and a barrier layer arranged between the outer and the inner layer, where the outer and inner layers are layers of gelatin; and (b) a pumpable filler material disposed within the shell, the filler comprises a hydrophilic component, a hydrophobic component, an amphiphilic component, or mixtures thereof; the barrier layer is resistant to migration of the hydrophilic, amphiphilic, and hydrophobic components of the filler material to the outer layer.