WO2003011257A1 - Composition and process the manufacture of soluble containers with improved gel-strength - Google Patents
Composition and process the manufacture of soluble containers with improved gel-strength Download PDFInfo
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- WO2003011257A1 WO2003011257A1 PCT/IN2002/000162 IN0200162W WO03011257A1 WO 2003011257 A1 WO2003011257 A1 WO 2003011257A1 IN 0200162 W IN0200162 W IN 0200162W WO 03011257 A1 WO03011257 A1 WO 03011257A1
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- cellulose ether
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- viscosity
- process according
- cellulose
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
- C08L1/08—Cellulose derivatives
- C08L1/26—Cellulose ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
- C08L1/08—Cellulose derivatives
- C08L1/26—Cellulose ethers
- C08L1/28—Alkyl ethers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
- C08L1/08—Cellulose derivatives
- C08L1/26—Cellulose ethers
- C08L1/28—Alkyl ethers
- C08L1/284—Alkyl ethers with hydroxylated hydrocarbon radicals
Definitions
- This invention relates to composition and process for molding polymer gels particularly cellulose derivative gels with enhanced gel strength resulting in soluble containers including capsules with flexible workability, consistent quality and low cost.
- Soluble containers find a variety of applications in several industries such as pharmaceutical, agrochemical, food, cosmoceuticals, nutraceuticals, agricultural etc.
- compositions of the aqueous solution of a capsule base for the production of non-gelatin capsules comprise of water-soluble cellulose derivative as base material, a gelatinizing agent and optionally an auxiliary for gelation.
- the process of production of capsules involves the immersion of a capsule molding pin in the aqueous solution of capsule base, drawing out the molding pin from the aqueous solution of this capsule base, and allowing the adhered solution to gel on the molding pin surface to form a film followed by drying and detaching the film from the molding pin and cutting the thus formed film to the required size.
- the film characteristics vary with changes in composition, gelling and drying conditions.
- US Patent Nos. 5,264,223 and 5,431 ,917 describe compositions and processes for the production of capsule using water-soluble cellulose derivatives such as hydroxypropylmethylcellulose (“HPMC”), hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methyl cellulose, and the like.
- HPMC hydroxypropylmethylcellulose
- HPMC has been indicated as the most preferred material in terms of film molding and mechanical strength at a condition of lower water content.
- the gelatinizing agent is carrageenan and the auxiliary for gelation is a water-soluble compound containing potassium ion, ammonium ion or calcium ion.
- HPMC is 5 to 25 parts by weight
- the gelatinizing agent is 0.1 % to 0.5% by weight
- the auxiliary for gelation is 0.01 % to 0.5% by weight.
- HPMCs themselves exhibit a wide range of physical characteristics especially rheology and thermogelling properties and that these properties determine the course of the gel properties and interact differently with the gelatinizing agents and the auxiliaries.
- the gelatinizing agents are selected from the group consisting of carrageenan, polysaccharide of tamarind seed, pectin, curdlan, gelatin, furcelleran and agar. These prior arts are directed to provide a hard capsule having no fragility under the condition of lower humidity due to the lower water content in equilibrium in the capsule film thereby preventing the cracking of the capsule film.
- US Patent No.5,756,123 and European Patent Document EP714656B1 disclose claims a capsule shell comprising of 79.6% - 98.7% by weight of a hydroxypropylmethyl cellulose, 0.03% - 0.5% by weight of carrageenan, and 0.14% - 3.19% by weight of potassium ion and/or a calcium ion obtained by drying a solution comprising 18%-28% by weight of HPMC whose 2% solution has a viscosity of 2.4 - 5.4 centistokes at 20 degrees centigrade as the base, 0.01 %-0.09% by weight of carrageenan as a gelling agent and 0.05%-0.6% by weight of potassium ion and /or calcium ion as co-gelling agent.
- the optimum viscosity range of the 2% aqueous solution of the HPMC to be 3.0 to 4.6 centistokes obtained from commercial HPMC or blends of commercially available HPMC in combination with the other components of the compositions described in this patent and in US Patents 5264223 and 5431917.
- the capsule shell exhibits disintegration ability equivalent to gelatin shells without degrading that ability even under special conditions containing much calcium ions.
- European patent document EP0946637B1 also discloses polymer compositions for film forming particularly hard and soft capsules, comprising water-soluble ethers, hydrocolloids and sequestering agents.
- the viscosity of the cellulose ether or blend is 3 to 15 cps in 2% aqueous solution at 20 degrees centigrade preferred 5 to 10 cps, especially preferred 6 cps.
- the composition as disclosed is 90% to 99.98% by weight of a cellulose ether or mixture of cellulose ethers with water contents of 2% to 10%; 0.01 % to 5% by weight of a hydrocolloid or mixtures of hydrocolloids and 0.01 % to 8% by weight of a sequestering agent or mixtures of sequestering agents.
- the hydrocolloids include synthetic gums such as gellan gum which may be combined with several other naturally occurring gums such as seaweeds, gaur gum etc.
- US Patent No. 4,001 ,21 1 describes improved thermogelling HPMC compositions in a hot pin dipping process for use in preparing pharmaceutical capsules by the pin dip coating process by utilizing a proper blending of the properties of water soluble methyl and C2-C3 hydroxyalkyl cellulose ethers to achieve an essentially Newtonian dip coating solution and a high thermal gel yield strength.
- the patent also discloses that the cellulose ether should have a relatively narrow molecular weight distribution. Blends of low viscosity methylcellulose and hydroxypropylmethyl cellulose provide particularly suitable dip solution properties, gel yield strength and capsule dissolution rates.
- German Patent document DE19926714 discloses another composition for producing hard capsules with a low moisture content, which comprises water 76.15% - 81 .04%, HPMC 18% - 20% (viscosity of 4-8 cps of its 2% solution at 20 degrees centigrade), gellan gum 0.8% - 1.2%, tri-sodium citrate 0.05% - 0.1 % , glycerol 0.01 % - 0.1 %, fatty acid ester 0.1 % - 0.5%.
- the capsules produced by composition of this patent do not break even though the moisture content is less than 10%, retain higher stability as compared to gelatin capsules but their degree of dissolution is approximately 5 minutes slower than gelatin capsules.
- compositions involving HPMC in the inventions disclosed in prior art continue to have weakness in the production process as the window of temperature, relative humidity (“RH") and air velocity for the drying process becomes very small and is of critical significance as small deviations in the drying conditions lead to star ends, wrinkles, gel rupture, verruca, striations etc.
- the set mass on the pin does not withstand the stress of drying resulting in defects leading to production of capsules of inconsistent quality.
- in the production line when such capsules with defects reach the joiner block they cause jamming and machine tripping adversely affecting the throughput of the manufacturing line.
- the residual stresses in the capsules can cause the capsule to become oval, loose shape, deform and often become unfit for the end user application.
- HPMC to be used must necessarily fall within the viscosity range specified and that above or below the ranges indicated cause problems in the immersion solution and produce films with undesirable characteristics.
- large size capsules even if made using the prior art compositions are not rigid for the wall thicknesses these are designed. The capsules collapse, deform and lose shape during subsequent storage resulting in high rejections.
- An object of the present invention is to provide improved compositions for use in processes for manufacture of capsules involving alkyl and /or hydroxyalkyl substituted cellulose of specific characteristics, gelling agents selected from a group of hydrocolloids and polysaccharides either singularly or as a mixture, solubilising agents, sequestering agents and other additives to manufacture capsules out of a base solution that results in a higher gel strength allowing the capsules to withstand stresses during drying and ensuring production of capsules of consistent quality with high throughput.
- capsules manufactured using such a composition provides protection against exposure to heat during transportation and storage compared to prior art compositions.
- Another embodiment of the present invention is to optionally use non-ionic surfactants such as sodium lauryl sulfate, Tween 80 and their like in the composition, for better wettability and uniform pickup on the molded pin, in the process for production of capsules.
- non-ionic surfactants such as sodium lauryl sulfate, Tween 80 and their like in the composition, for better wettability and uniform pickup on the molded pin, in the process for production of capsules.
- Yet another object of the present invention is to provide small and large size capsules of consistent quality for diverse applications.
- an improved polymer film composition for capsules such composition comprising:
- Fig. 1 represents the graph illustrating the increase in shear stress of the HPMC blend solution as it is cooled from 65°C to 20°C according to the present invention
- Fig. 2 shows the comparative thermal stability curves for the cap of the capsule according to the present invention and the prior art
- Fig. 3 Shows the comparative thermal stability curves for the body of the capsule according to the present invention and the prior art.
- the above disclosed improved polymer film composition for capsules comprises-
- said gelling agents in amounts from about 0.01% to about 12% of the weight of the blend of the two or more cellulose ethers(depending on the type of gelling agent which is a hydrocolloid or a mixture of hydrocolloids) ;
- said sequestering agents and / or co-gelling agent in amounts from about 25% to about 85% by weight of the gelling agent; with or without said solubilizing agent in amounts from about 2% to about 30% by weight of the blend of the ethers.
- the solubilizing agent used can be any additive to cause a solubilizing effect, such as PEG(Polyethylene Glycol) of different molecular weights viz, PEG 400 to PEG 4000 or 1 ,2 - propane di-ol (propylene glycol).
- PEG(Polyethylene Glycol) of different molecular weights viz, PEG 400 to PEG 4000 or 1 ,2 - propane di-ol (propylene glycol).
- the cellulose ethers are selected from a group consisting of Hydroxy propyl methyl cellulose, Hydroxy Propyl ethyl cellulose, Hydroxy ethyl methyl cellulose and the like.
- the above disclosed selective inventive polymer film composition of the invention is directed to avoid the prior art limitations of using only a low viscosity HPMC and help in providing additional strength to the gelled mass on the pin which gives the benefit of reduction in rejects like - wrinkles, striations, gel rupture, verruca etc. by reducing the criticality in controlling the drying conditions.
- the solubilizing agent helps in better hydration imparting better clarity and faster dissolution of cellulose ether in water during solution preparation.
- the present invention provides an improved process for manufacture of capsules wherein such process comprising the steps of:
- first cellulose ether a blend of first cellulose ether and a second cellulose ether, the first cellulose ether having a higher molecular weight than the second cellulose ether, with gelling agents selected from the group of hydrocolloids and polysaccharides along with sequestering agents / co-gelling agents and solubilizing agents as may be required in dip bath and feed tanks of capsule production system ; and
- such process of manufacture of capsules comprise:
- said gelling agents in amounts from about 0.01% to about 12% of the weight of the blend of the two or more cellulose ethers (depending on the type of gelling agent which is a hydrocolloid or a mixture of hydrocolloids) ;
- solubilizing agent in amounts from about 2% to about 30% by wt. of the blend of the ethers; dipping the dipping pins in said solution at a temperature from about 55°C to about 75°C in dip bath;
- cellulose ether would mean Hydroxy Propyl
- HPMC Methyl Cellulose
- HPMC Blend would mean Hydroxy Propyl Methyl Cellulose of any of the two or a blend of the two substitution types 2910 and 2906 of either high molecular weight or low molecular weight or both.
- HPMC herein after called as "HPMC Blend”
- HPMC Blend has any one or both substitution types.
- HPMC Blend would also mean, a blend of different molecular weight HPMCs, where at least one HPMC has a higher molecular weight than the other.
- a high molecular weight HPMC for the purpose of this invention would mean, a HPMC with a viscosity above about 16 cps of 2% aqueous solution at 20°C to about 4000 cps of a 2% aqueous solution at 20°C.
- a low molecular weight HPMC for the purpose of this invention would mean, a HPMC with a viscosity below about 15 cps of a 2% aqueous solution at 20°C to about 3 cps of a 2% aqueous solution at
- HPMC Blend for the purpose of this invention would also mean blend of two or more HPMCs having film strength from about 400 kg/cm 2 to about 600 kg/cm 2 ("low film strength HPMC") and another HPMC having a film strength from about 700 kg/cm 2 to about 1500 kg/cm 2 (“high film strength HPMC”).
- the HPMC Blend would consist of such HPMCs with different film strengths, where atleast one HPMC would be a high film strength HPMC.
- Film strength is defined here as the tensile strength of a 100 micron thickness HPMC film from 3% moisture content.
- the film strength is measured on a Shimadzu autograph tensile test device as per the prescribed standard procedures at a temperature from 20°C to about 25°C at an RH of 65%. (Ref: Metolose Brochure of Shin-Etsu Chemicals, Japan)
- the amount of the mixture of the HPMC Blend is preferably about 80% to 99.98% by capsule weight.
- the viscosity of the high molecular weight HPMC ranges from about 16 cps to about 4000 cps in 2% aqueous solution at 20°C and that of the low molecular weight HPMC from about 3
- the preferred viscosity of the high molecular weight HPMC is from about 20 cps to about 1000 cps & especially preferred is about 35 cps to 200 cps.
- the preferred viscosity of the low molecular weight HPMC is from about 3 cps to about 12 cps and the most preferred is about 3 cps to about 7 cps in 2% aqueous solution at 20°C.
- the resultant viscosity of the blend of the two or more HPMCs, wherein at least one is a high molecular weight HPMC, is from about 6 cps to about 50 cps, preferably about 15 cps to about 42 cps and most preferably from about 23 cps to about 34 cps in 2% aqueous solution at 20°C.
- One or more hydrocolloids used in the composition of the present invention include such items as synthetic gum or mixture of more than one synthetic gum, which are capable of gelling with or without the addition of alkaline or alkaline earth metal ions.
- Mixtures of gums may include natural seaweeds, natural seed gums, natural plant exudates, natural fruit extracts, bio-synthetic gums, bio-synthetic processed starch or cellulosic materials. These include Ispaghula husk derived from the Plantago seed of Plantago ovata Forsk.
- Fibrolax Fibrolax
- Fybrogel Isogel
- Regulan Psyllium hydrophilic mucilloid
- Psyllium hydrocolloid Psyllium seed gum
- Effer-Syllium Fiberall
- Metamucil Perdiem Fiber
- Serutan which are obtained from the epidermis of the Plantago ovata seeds.
- Such mixtures may also include alginates, agar gum, guar gum, locust bean gum (carob), carrageenan, tara gum, gum arabic, ghatti gum, Khaya grandifolia gum, tragacanth gum, karaya gum, pectin, arabian (araban), xanthan, gellan, starch, Konjac mannan, galactomannan, funoran, and other exocellular polysaccharides of which are preferred the exocellular polysaccharides, such as xanthan, acetan, gellan, welan, rhamsan, furcelleran, succinoglycan, scleroglycan, schizophyllan, tamarind gum, curdlan, pullulan, dextran.
- alginates agar gum, guar gum, locust bean gum (carob), carrageenan, tara gum, gum arabic, ghatti gum, Khaya grandifolia gum, trag
- gums that can be used are kappa-carrageenan or gellan gum, which may be used singularly or as mixtures.
- a mixture consisting of Xanthan gum, Locust Bean gum (carob), agar & kappa-carrageenan can be used as a gelling agent to produce gelling properties without the need to use a co-gelling agent in the composition.
- Such gums are also commercially available for example, TIC PRETESTED® Agaroid RS-507 manufactured by TIC Gums, Inc.,
- the ratios of each of the gums in the TIC PRETESTED® Agaroid RS-507 are - Xanthan gum is about 25% to 35%, Locust Bean gum (carob) is about 30% to 40%, agar is about 30% to 50% and carrageenan is about 15% to 25% standardized with dextrin about 1.5% to 3%.
- the amount of gum present in the composition is preferably about
- One or more sequestering agents may be used, the preferred ones being ethylenediaminetetraacetic acid, acetic acid, boric acid, citric acid, gluconic acid, lactic acid, phosphoric acid, tartaric acid, or salts thereof, metaphosphates, dihydroxyethylglycine, lecithin or beta cyclodextrin and combinations thereof. Especially preferred is ethylenediaminetetraacetic acid or salts thereof or citric acid or salts thereof.
- the sequestering mechanism can be adjusted by addition of either monovalent or divalent cations, such a Ca++, Mg++, K+, Na+, Li+, NH 4 + or the like.
- potassium chloride can be used as a co- gelling agent.
- the amount for both the sequestering agent or the co- gelling agent is preferably from about 25% to about 85%, by weight relative to the gelling agent, more preferably from about 40% to about 75%.
- silicon di-oxide may be added to improve the flow of capsules, the quantity of which from about 0.01 % to about 2% of the total weight of the HPMC Blend, more preferably from about 0.2% to about 0.8%.
- Additives ordinarily used in hard capsules such as dyes and pigments may be added from 0% to about 10% of the weight of blended HPMC.
- a co-gelling agent or a sequestering agent is added to hot water at a temperature of at least 85°C followed by the addition of a gelling agent under high shear mixing.
- HPMC Blend high & low viscosity
- the temperature is maintained from 65°C
- the solution is then transferred to dipbaths and feed tanks, which are attached to the conventional gelatin capsule production system.
- the solution temperature for dipping is maintained about 55°C to 75°C. After dipping, the capsules are kept under cold air at
- the dipping pins were then transferred for drying at about 20°C to 35°C and kept under air flow under a velocity from 500 FPM to 2000 FPM. Under this air velocity the capsules do not form star ends or wrinkles. After half an hour the capsules are transferred to another zone for drying at a temperature of 27°C to 35°C under air velocity from 1000 FPM to 3000 FPM to achieve stripping moisture from 4% to 10%.
- a dry blend of all the dry ingredients such as HPMC Blend, gum, gelling aids or sequestering agents is prepared in a blender and then added to the Mixer by vacuum suction or manually for solution preparation.
- Table - 1 illustrates the different blending ratios used -
- Concentration of the dipping solution described in each trial was kept from 13% (w/w) to 20% (w/w).
- Citric acid (216 gm) was dispersed in DM water (51 kg) at a temperature of
- Capsules were produced by inserting the dipping molds into the solution, then drawing out, exposing it at 23°C air for gelling and subsequently drying, stripping, cutting & joining.
- the drying temperatures ranged from 25°C to 35°C and the velocities of drying air ranged from 1000 FPM to 3000 FPM.
- Potassium Chloride 150 gm was dispersed in about 85°C DM water (51 kg), followed by addition of /cappa-Carrageenan (300gms). HPMC Blend (10 kg) was then added followed by addition of propylene glycol (300 gm). The mixture was kept under stirring at about 65°C for about 8 hours.
- Capsules were produced by inserting the dipping moulds into the solution, then drawing out, exposing under 25°C air for gelling and subsequently
- a mixture of Agar, Xanthan gum, Locust bean gum and Carrageenan (150 gm) available as a ready mix under the name of TIC PRETESTED® Agaroid RS-507 manufactured by TIC Gums, Inc., Maryland USA was dispersed in about 85°C DM water (25kg).
- HPMC Blend (5 kg) was then added followed by addition of propylene glycol (150 gm). The mixture was kept under stirring for 9 hours at a temperature around 75°C.
- Capsules were produced by inserting the dipping molds into the solution, then drawing out, exposing under about 25°C air for gelling and subsequently drying, stripping, cutting & joining.
- the drying temperatures ranged from about 25°C to a maximum of 35°C and the velocities ranged from about 1000 FPM to about 3000 FPM.
- Citric Acid (0.72 gm) was dispersed in DM water (990gms) at a temperature around 85°C, followed by addition of gellan gum (1 gm). A 1 :1 blend of Xanthan gum & LBG (carob) (1 gm) was added. HPMC Blend (200 gms) was then added. The mixture was kept under stirring for 8
- Capsules were produced by inserting the dipping molds into the solution, then drawing out, exposing under 25°C air for gelling and subsequently drying, stripping, cutting & joining.
- the drying temperatures range from 25°C to 35°C and the velocities of airflow ranging from about 1000 FPM to about 3000 FPM.
- Potassium Chloride (1 gm) was dispersed in 85°C DM water (1001 gms), followed by addition of /cappa-Carrageenan (2 gms), followed by addition of LBG (carob) (2 gms). HPMC Blend (200 gms) was then added. The mixture was kept under stirring for about 7 hours about 65°C.
- Capsules were produced by inserting the dipping molds into the solution, then drawing out, exposing under 25°C air for gelling and subsequently drying, stripping, cutting & joining.
- the drying temperatures range from 25°C to 35°C and the velocities ranged from about 1000 FPM to about
- Citric Acid 11 .25 gms was dispersed in 85°C DM water (24.8kg), followed by gellan gum (25 gms). Potassium Chloride (1 1 .25 gm) was then added, followed by addition of /cappa-Carrageenan (25gms). HPMC Blend (5 kg) was then added. The mixture was kept under stirring for 5 hours about 62°C
- Capsules were produced by inserting the dipping molds into the solution, then drawing out, exposing under 25°C air for gelling and subsequently drying, stripping, cutting & joining.
- the drying temperatures ranged from
- Potassium Chloride (44.4 gms) was dispersed in 85°C DM water (48.82 kgs), followed by addition of /cappa-Carragenan (98.4 gms). HPMC Blend (9.86 kgs) was then added. The mixture was kept under stirring for 6 hours at 55°C.
- Capsules were produced by inserting the dipping molds into the solution, then drawing out, exposing under 25°C air for gelling and subsequently drying, stripping, cutting & joining.
- the drying temperatures ranged from 25°C to 35°C and the velocities ranged from about 1000 FPM to about 3000 FPM.
- DM Water at 88°C (73.6 kgs) was taken in a tank. Added a blend of EDTA-sodium salt (91 gms) and potassium acetate (150 gms) to the DM water under stirring at 178 rpm. After 20 mins, gellan gum (142 gms) was added. Under stirring then added HPMC blend (17 kgs). Continue stirring for 7 hours. Solution temperature to be maintained at 58°C.
- Capsules were produced by inserting the dipping molds into the solution, then drawing out, exposing under 25°C air for gelling and subsequently drying, stripping, cutting & joining.
- the drying temperatures ranged from 25°C to 35°C and the velocities ranged from about 1000 FPM to about 3000 FPM.
- Table 2 shows a sample set of capsule sizes produced:
- HPMC Blend solutions of different compositions were prepared.
- a sample was taken in a Brookfield standard small sample adaptor SC4 (16ml).
- the spindle used was S-29.
- the small sample adaptor was placed in the Brookfield standard water-jacketed chamber (13R).
- the starting temperature of the sample was maintained at 65°C.
- the program for viscosity checking was started.
- the spindle (S-29) speed was 15 rpm, the corresponding shear rate was 3.75 sec "1 and the spindle was rotated continuously. Cooling of the solution was then started.
- the sample was cooled to 20°C at a constant rate. A data point was captured every five seconds.
- the graph clearly indicates the increase in gel strength for the HPMC Blend composition.
- Fig-1 Represents the shear stress of the HPMC solution as it is cooled from 65°C to 20°C. The figure clearly indicates the rise in shear stress in Newton per square meter.
- TFR Time of First Release
- TTR Time of Total Release
- TEST-2 Dissolution (%) of capsules after exposure to formaldehyde (HCHO) for one hour & storage in sealed bags for 72 hours.
- Test-1 & Test-2 show that the inventive product does not exhibit any cross-linking with formaldehyde that hinders disintegration and dissolution.
- the moisture of the capsules was progressively reduced by exposure to lithium chloride.
- the capsules were then tested for brittleness using the rod method. Precentage of capsules brittle was recorded for each moisture content.
- the first indication of heat damage is a reduction in diameter.
- the initial diameter of the samples was measured. These were then exposed to 44°C in an oven. The diameters of cap & body were then measured every 10 minutes. The readings were then tabulated and a graph plotted of drop in diameter (in microns) against the time of exposure. The graphical representation is shown as Figure-2 & Figure-3.
- Comparative product 1 is size 0 cellulose capsule as disclosed in the European patent document EP0946637B1.
- Comparative product 2 is sizeO cellulose capsule as disclosed in the European patent document EP714656B1.
- Capsules or soluble containers prepared as per this invention find applications in drugs and pharmaceuticals, agrochemical industry, packaging in food industry, cosmoceuticals, and nutraceuticals.
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Abstract
Description
Claims
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Cited By (9)
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EP1693056A1 (en) | 2005-02-21 | 2006-08-23 | Suheung Capsule Co Ltd. | Cellulose hard capsule shell with enhanced mechanical film strength containing iota-carrageenan and agar |
WO2007086586A1 (en) * | 2006-01-24 | 2007-08-02 | Qualicaps Co., Ltd. | Low-moisture-content hard capsule and production method therefor |
WO2009061821A3 (en) * | 2007-11-09 | 2010-01-28 | Union Carbide Chemicals & Plastics Technology Llc | Cellulose ether coating compositions and method |
US20100168410A1 (en) * | 2006-10-27 | 2010-07-01 | Pfizer Products Inc. | Hydroxypropyl Methyl Cellulose Hard Capsules and Process of Manufacture |
JP2013231185A (en) * | 2013-06-12 | 2013-11-14 | Pfizer Products Inc | Hard hydroxypropylmethyl cellulose capsule and manufacturing method |
WO2019020134A3 (en) * | 2017-07-24 | 2019-03-28 | Novamed S.A | Hard, acid-resistant capsules having a low gelling adjuvant content |
US20190224128A1 (en) * | 2018-01-19 | 2019-07-25 | Suheung Co., Ltd. | Process for preparing hypromellose hard capsule using thermogelation |
WO2021045151A1 (en) * | 2019-09-04 | 2021-03-11 | 信越化学工業株式会社 | Film molding composition and film |
CN113388162A (en) * | 2020-03-13 | 2021-09-14 | 信越化学工业株式会社 | Film-forming composition and film |
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EP0714656A1 (en) * | 1994-12-01 | 1996-06-05 | Japan Elanco Company Limited | Capsule shell compositions and their use |
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