AU2001255429A1

AU2001255429A1 - Compositions and films for capsule manufacture

Info

Publication number: AU2001255429A1
Application number: AU2001255429A
Authority: AU
Inventors: Haiyong Haung; Robert Schmitt
Original assignee: Union Carbide Chemicals and Plastics Technology LLC
Current assignee: Union Carbide Chemicals and Plastics Technology LLC
Priority date: 2000-07-21
Filing date: 2001-04-17
Publication date: 2002-02-05
Also published as: KR20030023709A; BR0112599A; EP1305011A1; JP2004504445A; CA2416257A1; MXPA03000624A; WO2002007711A1

Description

COMPOSITIONS AND FILMS FOR CAPSULE MANUFACTURE

Field of the Invention

The present invention relates to alkylene oxide polymer containing compositions which can be formed into flexible films having properties suitable for replacement of gelatin containing films in the manufacture of soft or hard shell capsules. The present invention further relates to processes for forming such alkylene oxide containing polymer films and the use of such films in the manufacture of soft shell capsules on conventional encapsulation equipment such as a rotary die machine.

Background of the Invention

Films made from gelatin containing compositions are commonly used in the manufacture of capsules, particularly soft capsules for the delivery of a variety of liquid or solid ingredients in pharmaceutical, agricultural and other applications. Such films are generally strong and tough and have processing properties which make them suitable for use in the manufacture of capsules. However, gelatin is a protein material produced by hydrolysis of collagen from animal bones and connective tissues. Since gelatin is derived from animal sources, there are often inconsistencies in product quality from batch to batch. The physical and chemical properties of gelatin are a function of the source of the collagen, the method of rendering and refining the crude feed stock, and the chemical nature of impurities and additives which may be present. Trace aldehyde impurities and/or aldehyde breakdown products from capsule filling material can react with and cross-link gelatin causing capsule failure. Additionally, the use of animal derived materials, such as gelatin, has come under regulatory review due to concerns regarding the potential transmission of animal based illness and there is growing resistance among the general population to acceptance of gelatin based capsules which are to be taken internally.

Accordingly, there is a need for new film forming compositions derived from nonanimal sources which can be used as a replacement for gelatin based films in the manufacture of capsules, in particular capsules for use in pharmaceutical and other applications where the capsules are to be ingested by humans.

The prior art discloses many efforts to replace gelatin compositions in the manufacture of capsules. For example, starch and cellulose compositions are disclosed in US Patent Nos. 4,738,724 and 5,756,036 and in PCT Publication Number WO 98/27151. U.S. Patent No. 3,164,560 discloses replacing a portion of the gelatin in film forming compositions with poly(alkylene oxide) resin to improve extensibility and flexibility. US Patent Nos. 4,774,092 and 5,965,150 disclose efforts to make capsules from poly(alkylene oxide) compositions. PCT Publication No. 97/35537 discloses manufacturing capsules from a variety of nongelatin materials including poly(ethylene oxide), polyvinyl alcohol, cellulose and starch among others. PCT Publication No. WO 99/40156 discloses manufacturing capsules from compositions containing a mixture of different molecular weight poly(alkylene oxide) polymers in which water is used to compatibilize the mixture of polymers. None of these prior art efforts have resulted in films having all of the physical and mechanical properties required to successfully replace gelatin films in the commercial manufacture of capsules. Summary of the Invention

In accordance with the present invention, there are provided thin flexible films made from compositions containing poly(alkylene oxide) polymers which can replace gelatin films in the manufacture of capsules. The poly(alkylene oxide) polymer containing films of the present invention are prepared by blending a poly(alkylene oxide) polymer component with an appropriate amount of water and optionally a plasticizer and/or other ingredients and extruding or otherwise forming a thin flexible film which is particularly suitable for the formation of capsule shells. The compositions of the present invention typically yield a film with mechanical properties in desired ranges, e.g., having a stress of less than 250 psi at a strain of 100% as determined by a mechanical tensile test in accordance with ASTM D882-97 and an Indentation Index of less than 8 as determined by the HH Indentation Test described hereinafter. The poly(alkylene oxide) polymer containing films of the present invention can be used in known processes and apparatus for the manufacture of capsules for pharmaceutical, agricultural and other applications.

Detailed Description of the Invention

The compositions of the present invention suitable for forming films useful in the manufacture of capsules comprise;

(a) from about 49 to about 85% by weight, based on the total weight of the composition, of a polymer component which contains at least about 30% by weight, based on the weight of said polymer component of a poly(alkylene oxide),

(b) from about 14% to about 50% by weight of water, and

(c) from 1 to about 30% by weight of a plasticizer component. These compositions may be formed into the films of the present invention by known means such as extrusion. The thin, easily extensible, films of the present invention which are suitable for the preparation of capsules comprise;

(a) from about 49 to about 85% by weight, based on the total weight of the film of a polymer component containing at least about 30% by weight, based on the weight of said polymer component of a poly(alkylene oxide),

(b) from about 14% to about 50% by weight of water, and

(c) from 1 to about 30% by weight of a plasticizer component, and have a stress of less than 250 psi at a strain of 100% as determined by a mechanical tensile test in accordance with ASTM D882-97 and an Indentation Index of less than 8 as determined by the HH Indentation Test described herein.

The poly(alkylene oxide) polymers used to obtain the films of the present invention are prepared from alkylene oxide monomers containing from about 2 to 5 carbon atoms per molecule, e.g., ethylene oxide or propylene oxide, as well as copolymers and derivatives thereof. Polymers of a desired molecular weight may be obtained directly from the polymerization of the alkylene oxide monomers or by blending poly(alkylene oxide) polymers of different molecular weights. As used herein, the term "molecular weight" means number average molecular weight. Methods for determining number average molecular weight such as gel permeation chromatography, light scattering techniques and rheological measuring techniques are known to those skilled in the art. The molecular weights used in this specification were determined by rheological measurements. These alkylene oxide polymers useful in the present invention are water soluble and have a molecular weight of from about 100,000 to 8,000,000 g/mol.

Preferably, the poly(alkylene oxide) polymers used to obtain the films of the present invention comprise ethylene oxide polymers. The ethylene oxide polymers include, for example, homopolymers of ethylene oxide and copolymers of ethylene oxide with one or more polymerizable comonomers. The particular comonomer is not critical to the present invention and may contain hydrocarbon substituents, such as, for example, alkyl, cycloalkyl, aromatic, alkene (also referred to as alkylene) or branched alkyl or alkene groups; provided, however, that the water solubility or water-dispersibility is maintained. Methods of preparing ethylene oxide polymers useful in the present invention are well known in the art. See for example, U.S. Patent Nos. 2,969,403 issued to Helmut et al., 3,037,943 issued to Bailey et al., 3,167,519 issued to Bailey et al., 4,193,892, issued to Goeke et al. and 4,267,309 issued to Goeke et al. Poly(alkylene oxide) polymers useful in the present are commercially available, for example, from Union Carbide Corporation, a subsidiary of Dow Chemical Company, under the tradename POLYOX^® Water Soluble Resins. These homopolymers of ethylene oxide have a molecular weight of from about 100,000 to 8,000,000 g/mol.

A single molecular weight grade of poly(alkylene oxide) polymer or a blend of two or more grades of such polymers in appropriate proportions can be used. The molecular weight of the poly(alkylene oxide) chosen for use in preparing a film of the present invention will largely be determined by the type of capsule to be manufactured and its intended use. In general, the molecular weight of the polymer is chosen on the basis of the time required for the capsules made therefrom to dissolve in the fluid environment present in the intended use. For example, to obtain films having rapid dissolution properties in a gastrointestinal environment similar to soft gelatin capsules, the poly(alkylene oxide) polymer component will normally have a molecular weight in the range of 200,000 to 400,000 g/mol., whereas higher molecular weight polymers are suitable for slower dissolving capsules. The poly(alkylene oxide) containing polymer component of the compositions from which the films of the present invention are formed may comprise additional polymers in order to achieve desired properties. Such other polymers include, for example, naturally occurring and synthetic neutral, cationic, and anionic polymers, e.g., polysaccharides and derivatives thereof, hyaluronic acid, other cross- linked polyalkylene oxides, polyvinyl pyrrolidones, polycaprolactones, polyvinyl acetates and polycarboxylic acids, polyacrylic acid and polyvinyl acetate. The polysaccharides include naturally occurring, biosynthesized and derivatized carbohydrate polymers and mixtures thereof. Such materials encompass high molecular weight polymers composed of monosaccharide units joined by glycosidic bonds. These materials may include, for example, the entire starch and cellulose families; pectin; chitosan; chitin; the seaweed products such as agar and carrageenan; alginate; the natural gums such as guar, arabic and tragacanth; bio-derived gums such as xanthan; and the like. Common polysaccharides include cellulosics conventionally employed for the preparation of cellulose ethers, such as, for example, chemical cotton, cotton linters, wood pulp, alkali cellulose and the like. Such materials are commercially available. The molecular weight of the polysaccharides typically ranges from about 10,000 to 2,000,000 grams per mole. Preferably, the polysaccharides are etherified by reacting the polysaccharide with an alkylene oxide, e.g., ethylene oxide, propylene oxide or butylene oxide or otherwise derivatized by techniques known to those skilled in the art.

When such other polymers are used in the film forming compositions of the present invention, they are typically present in amounts of less than about 70% by weight, and more typically from about 10 to 40% by weight, based on the total weight of the polymer component. Particularly good results have been obtained when the polymer component contains at least about 50% by weight poly (ethylene oxide).

Unless otherwise indicated, the weight percentages of the various components of the film forming compositions of the present invention are based on the total weight of the composition, including the polymer component, water, plasticizers and other components as hereinafter described.

The poly(alkylene oxide) polymer containing compositions used to form the films of the present invention contain water in an amount of from about 14 to about 50% by weight, more preferably from about 20 to about 35% by weight, based on the total weight of the film forming composition. In general, higher molecular weight poly(alkylene oxide) polymers require larger amounts of water to achieve the same flexibility compared to low molecular weight poly(alkylene oxide) polymers. The water should present in an amount sufficient to be effective as an internal plasticizer when the compositions are used to form the films of the present invention, e.g. by extrusion. Care must be taken to maintain the water content of the finished films of the present invention above about 14 % by weight when used in the manufacture of capsules to obtain the physical and mechanical properties necessary to make them suitable to replace gelatin based films.

Compounds customarily used as plasticizers may also advantageously be included in the compositions from which the films of the present invention are formed. Such plasticizers modify the films' properties making them softer and more ductile and also help maintain the water content in the films, which is believed to enhance the flexibility and sealability of the films during the encapsulation step. Compounds which are particularly useful as plasticizers in the present invention are capable of forming hydrogen bonds with poly(alkylene oxide). Examples of such compounds include pol hydric alcohols such as glycerin, propylene glycol, sorbitol and the like, carboxylic acids and their derivatives including adipic acid, triethyl citrate and the like, and sugars such as glucose, fructose, xylose and the like. All of the plasticizers may be used alone or in mixture thereof. Plasticizer compounds may be present in the film forming compositions of the present invention in an amount of from 1 to about 40% by weight, preferably from about 5 to about 30 % by weight.

Other well recognized components may be present in the film forming compositions of the present invention. Such other components include, for example, stabilizers, preservatives, antioxidants, colorants, flavorants, opacifing agents, processing aids, fillers and the like. The choice of one or more such other component and the amount used for any particular application is well within the skill of those familiar with the art.

The films of the present invention may be prepared with conventional apparatus by conventional film forming processes, preferably extrusion. Typically, prior to forming the films, the polymer component containing the poly(alkylene oxide) having the selected molecular weight is first uniformly blended with water and optionally a plasticizer and any other components in a conventional mixer such as a Henchel mixer, V blender or Hobart mixer. Preferably, the various components are added separately to an extruder with solid components being added by way of a metered feeder and liquid components being added by way of a metered pump, and formed into a homogeneous mixture inside the extruder. The water content of the blended composition should be sufficient to avoid excessive extrusion torque but not so great as to produce films which lack sufficient tensile strength to maintain their shape. Caution should be taken to avoid excess loss of water during film production and transportation. For example, during extrusion, the extruder and die temperatures are kept below the boiling point of water to prevent excess water evaporation. The techniques and conditions to be employed in extruding the films of the present invention will be readily apparent to the skilled artesian and are described, for example, in U.S. Patent 3,941,865 which is incorporated herein by reference.

The films of the present invention are easily extensible and for most applications will have a thickness of from about 5 to about 50 mils. The films of the present invention are preferably self sealing, that is, the films should be able to seal onto themselves with the help of elevated temperature, pressure, or both, and without the necessity of being solvated.

A preferred use for the poly(alkylene oxide) containing films of the present invention is in the manufacture of soft capsules. Quite advantageously, the films of the present invention can replace gelatin based films in the manufacture of soft shell capsules. In general, the soft shell capsules can be prepared by a rotary die process in which they are formed, filled, and sealed in a single operation. An example of such a process is described in PCT International Publication No. WO 97/35537. Since the poly(alkylene oxide) containing films of the present invention expel water quickly even at room temperature, capsules prepared from such films may be dried rapidly thus saving energy and reducing production times. Capsule shells made from the films of the present invention have a very low water content, typically from 0 to about 5%, depending on film composition and resist moisture uptake even in relatively humid conditions while providing excellent mechanical strength. Thus, the films of the present invention are ideal for encapsulating moisture sensitive materials and meet other standard requirements for capsules including maintenance of capsule shape under external pressure, good solubilit in gastro-intestinal fluid and stability for long term storage.

The films of the present invention may be used to encapsulate a wide range of substances in the form of solids or liquids. Those skilled in the art will recognize that capsules prepared from the films of the present invention will have a variety of industrial and personal care uses. For instance, the capsules can be used for the oral delivery of pharmaceutically active agents to humans and animals. For such applications, the liquid filing material comprises a physiologically acceptable carrier such as those used in gelatin capsules including, for example, poly(ethylene glycol), vegetable oil, lecithin, mineral oil, etc. In addition, the capsules can be used in personal care applications, e.g., hair care and skin care formulations, to deliver oils, vitamins, proteins, polymers and other personal care ingredients. The capsules can also be used, for example, to provide bath oil beads, fragrances and time released ingredients. Further, the capsules can be used in the manufacture of paint balls and other recreational products. Moreover, the capsules can be employed in a variety of industrial uses, such as, for example, in the delivery of inks, catalysts, initiators, enzymes, and the like. The size and shape of the capsules and details concerning the selection and amounts of the appropriate filling materials and active ingredients can be determined by those skilled in the art and are not a critical part of the present invention.

The processability of the film to form soft shell capsules can be determined by the tensile test and by the "HH Indentation Test". In the tensile test, "stress" is a measure, in pounds per square inch (psi), of the force per unit area required to achieve a certain strain and is determined in accordance with the procedures of ASTM D882-97. "Strain" is determined by subtracting the length of a piece of film to be tested at rest from the length of the piece of film after it has been stretched and dividing that number by the length of the piece of film at rest. Thus, a strain of 100% is achieved when a piece of film is stretched to a length double its length at rest.The "HH Indentation Test" described and used herein, measures the ability of a film to be deformed into a half capsule shape. The test is performed using a TA- XT2 Texture Analyzer (Stable Micro Systems, Haslemere, UK). A piece of film to be tested is placed between two plates which are bolted together. Each plate has a hole in its center exposing a circular section of the film sample approximately 0.6 inches in diameter. A probe comprising a cylindrical rod having a diameter of 0.5 inches and a rounded tip having a radius of 6.4mm is positioned to push against the exposed section of film. The Indentation Index represents the amount of force, in pounds, required to move the probe a certain distance when the probe is moving at a certain speed. The distance the probe travels represents the depth of the indentation the probe makes in the film. For purposes of defining the films of the present invention, the Indentation Index is determined using a film sample formed to a thickness of 25 mils with the probe moving at a speed of 1 mm/second and traveling a distance of 6.4 mm. To meet the requirements of the present invention, a film sample that is suitable to use on a typical soft-shell capsule encapsulation machine must have an Indentation Index value of less than 8.

The following Examples are provided for illustrative purposes and are not intended to limit the scope of the following claims. The molecular weight of the poly(alkylene oxide) polymers used in the examples is determined by rheolgical measurements. Tensile and elongation tests were conducted at room temperature using procedures conforming with ASTM Method No. D882-97 unless otherwise indicated. The concentrations of ingredients are provided in weight percent unless otherwise indicated. EXAMPLE 1

To a Henschel Mixer was added 2500 g of poly(ethylene oxide) having a molecular weight of 300,000 (POLYOX WSR N-750 manufactured by Union Carbide Corporation). Glycerin (830 g) was then added slowly while the mixture was blended until fine granules were obtained. Water (1427 g) was sprayed onto the mixture and the blending was continued for an additional 10 min. The above mixture was then extruded through a 2-inch wide slot die using a single screw extruder (Brabender PL2000) at a screw speed of 10 to 15 rpm. The temperature of all zones in the extruder and the die were maintained at about 90 °C. The extruded film was pulled from the slot die through a pair of nip rollers and then was collected on a wind-up roll.

The freshly extruded film was placed in an incubator with circulating air under controlled condition of 50% relative humidity at 25 °C. Samples were taken at different time intervals to determine the water content in the films. The results, which are shown in Table 1, indicate that the poly(ethylene oxide) based films lose water readily.

Table 1

Time 0 min 15 min 30 min 60 min 120 min

Water 25 2^~dδ ϊδlβ 6^~!θ8 14

Content

(wt%)

The mechanical properties of the extruded film were measured at various amounts of water remaining in the film. The water content and mechanical properties are presented in Table 2 for the machine direction and Table 3 for the transverse direction. Table 2

Water Yield Yield Tensile ElongaStress at in the Strength ElongStrength tion at 100% of film (psi) ation (psi) break strain (psi)

(wt. %) (%) (%)

20 130 12 214 1400 128

15 215 24 350 >2200 200

12 250 20 370 >2200 242

0 710 16 450 1700 514

Table 3

Water in Yield Yield Tensile ElongaStress at the film Strength ElongaStrength tion at 100% of (wt. %) (psi) tion (%) (psi) break strain (psi)

20 120 16 224 1400 123

15 207 20 303 >2200 230

13 231 16 310 >2200 246

0 638 12 450 1300 514

EXAMPLE 2

A mixture of POLYOX WSR N-750, glycerin and water was extruded on a Brabender^® Conical Twin Screw Extruder (Model CTSE- V) operated at low temperatures (feed 25-45 °C, barrel 50-90 °C, die 80-110 °C). The extruded film was collected in the same manner as described in Example 1. The screw speed was 20 to 50 rpm, and the torque was -2000 mg. The solid POLYOX WSR N-750 powder was meter-fed into the extruder with a K-Tron Volumetric Feeder Model K2MV-720, and the liquid containing water and glycerin was metered into the extruder with a MasterFlex Peristaltic Pump Model PM- 77914. Both the solid and liquid addition rates were controlled, so that the composition contains POLYOX WSR N-750/glycerin in a ratio of 4:1, and the water content in the finished extruded film was about 30 wt% .

The mechanical properties of the extruded film at various levels of water content are presented in Table 4 (machine direction) and Table 5 (transverse direction).

Table 4

Water Yield Yield Tensile Elonga* Stress at in the Strength ElongaStrength tion at 100% of film (psi) tion (%) (psi) break strain (psi) (wt%)

31 50 10 80 800 50

25 125 6 188 1300 125

20 208 14 300 1450 185

13 320 14 373 1400 240

0 710 20 568 1000 605

Table 5

Water Yield Yield Tensile ElongaStress at in the Strength ElongaStrength tion at 100% of film (psi) tion (%) (psi) break strain (psi) (wt.%)

30 73 10 109 500 100

23 152 6 286 1200 163

15 259 10 337 1400 227

0 635 10 635 400 510

Indentation tests were also performed to evaluate the processability of the extruded film in making soft shell capsule. This test was performed on a TA-XT2 Texture Analyzer (Stable Micro Systems, Haslemere, UK) in accordance with procedures described previously herein to measure the extension and elasticity of the film.

EXAMPLE 3

To a Henschel Mixer was added 1150 g of POLYOX N-750 and 165 g of hydroxypropyl cellulose (JF grade, Hercules). Glycerin (265 g) was added slowly while the mixture was blended until fine granules were obtained. Water (675 g) was sprayed onto the mixture and the blending was continued for an additional 10 min. The above mixture was extruded on a single screw extruder (Brabender PL2000) and the film was collected as described in Example 1. The mechanical properties of the extruded film at various levels of water content are presented in Table 6 (machine direction) and Table 7 (transverse direction).

Table 6

Water in Yield Yield Tensile ElongaStress at the film Strength ElongaStrength tion at 100% of (wt.%) (psi) tion (%) (psi) break strain (psi)

24 46 20 50 400 46

15 112 16 128 2000 120

12.5 314 26 557 >2200 257

7.5 413 26 560 >2200 345

4.1 543 30 657 >2200 485

0 700 20 675 2000 600

Table 7

Water Yield Yield Tensile ElongaStress at in the Strength ElongaStrength tion at 100% of film (psi) tion (%) (psi) break strain (psi)

(wt.%)

25 46 20 50 400 46

15 112 16 180 1800 140

13 320 20 467 2000 240

8.5 427 30 480 >2200 346

4.1 480 30 587 >2200 440

0 680 16 680 1850 600

EXAMPLE 4

POLYOX WSR N-750 and xylose in a ratio of 10:1 were first mixed for 2 minutes with a mortar and pestle. Water was then added slowly to the mixture in an amount sufficient to provide a total of 35 wt.% and the mixing was continued for an additional 10 minutes. The doughy mixture (-20 g) was transferred to a Brabender head mixer (D- 51, No 507) operated at 80 °C and 10 RPM. After mixing for 5 minutes, an aliquot of hot mixture was taken out and placed between two aluminum plates and was pressed on a hydraulic press at 2000 PSI and 90 °C. After pressing for 2 minutes, the film was released from the mold and sealed in a plastic bag. The mechanical properties of the compressed film at various levels of water content are presented in Table 8. Table 8

(wt.%) (%)

35 41 10 97 1650 60

29 117 10 205 2000 116

24 175 30 350 1800 175

18 213 10 475 >2200 225

14 444 20 667 >2200 388

9 486 18 760 >2200 485

0 1766 20 2255 2000 2000

EXAMPLE 5 Poly(ethylene oxide) having a molecular weight of 200,000 g/gmol (POLYOX WSR N-80) and glycerin in a weight to weight ratio of 5:1 were first mixed for 2 minutes with a mortar and pestle. Water was then added slowly to the mixture in an amount sufficient to provide a total of 20 wt.% and the mixing was continued for an additional 10 minutes. The doughy mixture (-20 g) was transferred to a Brabender head mixer (D-51, No 507) operated at 80 °C and 10 RPM. After mixing for 5 minutes, an aliquot of hot mixture was taken out, placed between two aluminum plates and pressed on a hydraulic press at 2000 PSI and 90 °C. After pressing for 2 minutes, the film was released from the mold and sealed in a plastic bag. The mechanical properties of the compressed film are presented in Table 9. Table 9

(wt.%) (%)

19 169 20 215 200 184

14 304 20 304 200 300

10 533 20 483 300 516

5 764 30 618 200 654

0 1174 20 795 200 946

EXAMPLE 6

POLYOX WSR N-80 and xylose in a w/w ratio of 10:1 were first mixed for 2 minutes with a mortar and pestle. Water was then added slowly to the mixture in an amount sufficient to provide a total water content of 35% and the mixing was continued for an additional 10 minutes. The doughy mixture (-20 g) was transferred to a Brabender head mixer (D-51, No 507) operated at 80 °C and 10 RPM. After mixing for 5 minutes, an aliquot of hot mixture was taken out and placed between two aluminum plates and was pressed on a hydraulic press at 2000 PSI and 90 °C. After pressing for 2 minutes, the film was released from the mold and sealed in a plastic bag. The mechanical properties of the compressed film are presented in Table 10. Table 10

Water Yield Yield Tensile ElongaStress at in the Strength ElongaStrengt tion at 100% of film (psi) tion (%) h (psi) break strain (psi)

(Wt.%) (%)

35 31 20 36 700 57

28 139 20 292 800 166

16 240 10 240 200 240

10 585 14 523 250 450

5 769 20 615 250 707

0 1738 30 1738 100 1070

EXAMPLE 7

Ellipsoidal shaped capsules were prepared from films of the previous examples on a small mold that simulates the action of an encapsulation rotary die. The film was heated gently just prior to sealing when water content was below 20% and required no heating when water content was about 30%. The resulting capsules had strong seals. The finished (dry) capsules appeared opaque and had a smooth surface and a strong seam. They retained their shapes well under external force. The capsules were filled with vegetable oil or poly(ethylene glycol). These capsules ruptured within 30 minutes in a dissolution test defined by U.S. Pharmacopeia, 24 rev.;.U.S. Pharmacopeial Convention: Rockville, MD, 2000; pp. 1941-1942 by stirring (50 rpm) at 37 °C in 0.1 N HC1 (1000 mL). In general, the capsules dissolve faster with higher plasticizer contents and thinner shells. Results of the disintegration test are presented in Table 11.

Table 11

Claims

What is claimed is:

1. A composition suitable for forming films useful in the manufacture of capsules comprising;

(a) from about 49 to about 85% by weight, based on the total weight of the composition of a polymer component containing at least aboμt 30% by weight, based on the weight of said polymer component of a poly(alkylene oxide),

(b) from about 14% to about 50% by weight of water, and

(c) from 1 to about 40% by weight of a plasticizer component.

2. The composition of claim 1, wherein said poly(alkylene oxide) is one or more poly(ethylene oxides) having a molecular weight of aboutl00,000 to about 8,000,000 g/gmol.

3. The composition of claim 1 wherein said polymer component contains at least about 50 % by weight, based on the total weight of said polymer component, of poly(ethylene oxide).

4. The composition of claim 3 wherein said poly(ethylene oxide) has a molecular weight of from about 200,000 to about 400,000 g/gmol.

5. The composition of claim 4 wherein said water is present in an amount of from about 14 to about 35% by weight and said plasticizer is present in an amount of from about 1 to about 30% by weight.

6. The composition of claim 5 wherein the plasticizer is a polyhydric alcohol, a carboxylic acid or a derivative thereof, a sugar or mixtures thereof.

7. A thin, easily extensible film suitable for the preparation of capsules comprising;

(b) from about 14% to about 50% by weight water, and

(c) from 1 to about 40 % by weight of a plasticizer component, said film having a stress of less than 250 psi at a strain of 100% as determined in accordance with ASTM D882-97 and an Indentation Index of less than 8 as determined by the HH Indentation Test described herein.

8. The film of claim 7 wherein said poly(alkylene oxide) is one or more poly(ethylene oxides) having a molecular weight of aboutl00,000 to about 8,000,000 g/gmol.

9. The film of claim 7 wherein said polymer component contains at least about 50% by weight, based on the total weight of said polymer component, of poly (ethylene oxide).

10. The film of claim 9 wherein said poly(ethylene oxide) has a molecular weight of from about 200,000 to about 400,000 g/gmol.

11. The film of claim 10 wherein said water is present in an amount of from about 14 to about 30% by weight and said plasticizer is present in an amount of from about 1 to about 30% by weight.

12. The film of claim 11 wherein the plasticizer is a polyhydric alcohol, a carboxylic acid or derivative thereof, a sugar or mixtures thereof.

13. The film of claim 7 which is self sealing upon heat and/or pressure.

14. The film of claim 7 which has a thickness of from about 5 to about 50 mils.

15. A method of forming a film suitable for use in the manufacture of capsules which comprises;

(a) forming a blend of

(i) from about 49 to about 85% by weight, based on the total weight of the composition of a polymer component containing at least about 30% by weight, based on the weight of said polymer component of a poly(alkylene oxide), (ii) from about 14% to about 50% by weight water, (iii) from 0 to about 50% by weight of a plasticizer component, and

(b) forming a film having a thickness of from about 5 to about 50 mils while retaining sufficient water whereby said film has a stress of less than 250 psi at a strain of 100% as determined in accordance with ASTM D882-97 and an Indentation Index of less than 8 as determined by the HH Indentation Test described herein.

16. A capsule prepared from the film of claim 7.