CA2263703A1 - A process for producing enteric coated pancreatin granules - Google Patents

A process for producing enteric coated pancreatin granules Download PDF

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Publication number
CA2263703A1
CA2263703A1 CA002263703A CA2263703A CA2263703A1 CA 2263703 A1 CA2263703 A1 CA 2263703A1 CA 002263703 A CA002263703 A CA 002263703A CA 2263703 A CA2263703 A CA 2263703A CA 2263703 A1 CA2263703 A1 CA 2263703A1
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Prior art keywords
pancreatin
granules
process according
coated
coating solution
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Abandoned
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CA002263703A
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French (fr)
Inventor
Kyung Hee Yi
Dong Woo Park
Hong Ryeol Jeon
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Il Yang Pharmaceutical Co Ltd
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Kyung Hee Yi
Il Yang Pharm Co., Ltd.
Dong Woo Park
Hong Ryeol Jeon
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Publication of CA2263703A1 publication Critical patent/CA2263703A1/en
Abandoned legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5052—Proteins, e.g. albumin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes

Abstract

A process for producing enteric coated pancreatin granules which comprises spraying the pancreatin powder with a coating solution at a high speed while floating the pancreatin powder at a low temperature to obtain the coated pancreatin granules is disclosed. The granules obtained thus are very stable at acidic pHs and for their tabletting

Description

A PROCESS FOR PRODUCING
ENTERIC COATED PANCREATIN GRANULES
FIEND OF THE INVENTION
The present invention relates to a process for producing enteric-coated pancreatin granules which are stable at acidic pHs and for their tabletting.
BACKGROUND OF THE INVENTION
Pancreatin is a digestive enzyme isolated from the pancreases of mammals, such as cows and pigs, having amylase, protease and lipase activities. It is known that pancreatin can treat cystic fibrosis, pancreatitis, pancreoprivic syndrome and similar conditions. The pancreatic enzymes, produced from the pancreas, are released into the duodenum, the pH of which is close to neutral or slightly alkaline. Under these pH
conditions, the released pancreatic enzymes are active and digestion of the food by the enzymes proceeds normally in the upper segment of the small intestine.
However, when pancreatin is administered exogenously to the patient in need of the treatment for pancreatin malfunction, the gastric conditions in the stomach, namely the presence of acid and pepsin, will irreversibly render the enzymes inactive. Under the acidic conditions the enzymes exhibit 10% to 40% of their normal activity. The acidic pH
especially influences lipase activity. Therefore, orally administered enzymes must be protected against inactivation due to gastric acid so that they remain intact during their transit through the stomach into the duodenum.
The best way to protect the enzymes is through application of an enteric coating.
Two techniques can be used to apply an enteric coating. The first technique, which is well known, involves mixing the pancreatin with an appropriate adjuvant, tabletting the resulting mixture, and applying an enteric coating to the tablets thus obtained. The pancreatin is often used in combination with other digestive enzymes, rather than as a single ingredient. As such, even those among the additional digestive enzymes working in the stomach may be coated and thereby they do not exhibit their benefits sufficiently in the stomach. The other technique is disclosed in U.S. Pat. Nos. 5,260,074 and 5,302,400. It consists of blending pancreatin with the appropriate adjuvant, binder, and organic solvent, granulating the blend, compacting the granulates into spherical particles, drying the spherical particles, and applying an enteric coating to the dried particles.
Specifically, the pancreatin is mixed with the appropriate binder, stabilizer, disintegrant, and organic solvents disclosed in U. S. Pat. No. 4,079,125, followed by granulation of the resulting mixture. The granules thus obtained are molded into beads by Marumerizer compaction and the resulting beads are coated. Alternatively, the pancreatin powder is mixed with a lubricant, and the resulting mixture is compacted into spherical plates using roller compaction, concave compaction or convex compaction. The plates thus obtained are ground, sieved, and coated without organic solvents. This technique is not advantageous as the activity of the enzyme is decreased by the solvent used during granulation and by the heat generated during compaction. The technique is also inefficient because it includes many steps. When the enteric coated granules are tableted, they must be stable against tabletting pressure and must be minute. As such, because the tableting pressure dissipates, the enteric coated granules can be molded without becoming brittle. However, the prior techniques cannot produce minute and uniform granules, and consequently do not result in enteric coated granules stable under acidic conditions and for tabletting.
Therefore, although pancreatin is advantageous when it is used as a complex preparation, i.e., tablet wherein gastric enteric compartments are formed by naked tabletting or gastric coating, there is still a need to develop enteric coated granules stable against tabletting pressure when used singly. We have achieved an improved enteric coating technique ensuring intact activity of the pancreatin in the gastric environment, rapid dissolution of the enteric coated granule in the intestine and stability of the coated granule against tabletting pressure.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides a process for producing enteric coated pancreatin granules which comprises spraying the pancreatin powder with a coating solution at a high speed while floating the pancreatin powder at low temperature to obtain fine coated pancreatin granules, if necessary, again spraying the resulting fine granules with another coating solution, identical to or different from the first coating solution, at a high speed while floating the fine granules at low temperature to produce the coated pancreatin granules.
In another aspect, the present invention provides a process for producing pancreatin tablets that comprises spraying the pancreatin powder with a coating solution at a high speed while floating the pancreatin powder at low temperature to obtain fine coated pancreatin granules, if necessary, again spraying the resulting fine granules with another coating solution, identical to or different from the first coating solution, at a high speed to produce the coated pancreatin granules, mixing, based on the total weight of the tablets, from 5% to 80% of the resulting coated granules with a pharmaceutically acceptable adjuvant, and tabletting the resulting mixture.
DETAILED DESCRIPTION OF THE INVENTION
The coating base for this invention includes corn protein extract, sodium alginate, alginic acid, methacrylic acid-ethyl methacrylate copolymer, shellac, carbopol (carbomer~, carboxyvinyl-polymer), hydroxypropylmethylcellulosephthalate, hydroxy-propylmethylcellulose acetate succinate, hydroxypropylmethyl acetate succinate, carboxymethylcellulose, cellulose acetate phthalate, hydroxypropylcellulose, ethyl-cellulose, methylcellulose, polyvinyl acetate phthalate, soybean protein, wheat protein, chitin, chitinic acid, agar, carrageenan, pectin, guar gum, locust bean gum, xanthan gum, gellan gum, arabic gum, and medium chain fatty acid of 6 to 12 carbons. These can be used singly or as a mixture of two or more. The coating base can be used in amounts of from 1 % to 250% based on the total weight of the pancreatin used, preferably from 50%
to 180% by weight.
The plasticizer used for the coating of the present invention includes polyethylene glycol, glycerin fatty acid ester, sorbitan fatty acid ester, propylene glycol, glycerin, triethyl citrate, triacetin, cetyl alcohol, and stearyl alcohol. These can be used as singly or as a mixture of two or more. The plasticizer can be used in amounts of from 1 % to 50% based on the total weight of the pancreatin used, preferably from 5% to 30% by weight.
If the coating base and plasticizer are used in ratios other than those given above, disintegration of the coated granule is delayed or the coating becomes unstable in the gastric fluid. Consequently, the pancreatin either does not act rapidly or its activity decreases.
The solvent for the coating solution of the present invention includes water, alcohol, acetone, acetonitrile,methylene chloride, ether, hexane, chloroform,1,4-dioxane, tetrahydrofuran, dimethyl sulfoxide, ethyl acetate, methyl acetate, or a mixture thereof.
Many fluid beds or similar devices can be used for coating. The fluid bed SFC-MINI (Freund Co., Japan) was used for this invention. The temperature of influx air ranges from 35°C to 70°C. The temperature of the granules must be at least 25°C during the whole procedure in order to prevent aggregation and crumbling of the granules. It is preferable to adjust the temperature of the granules within a range of 25 °C to 60°C during the procedure because the enzyme titer can reduce at temperatures in excess of 60°C.
The following examples illustrate the composition and process forthe preparation of enteric coated pancreatin granules in accordance with the present invention, without limiting the scope thereof.
EXAMPLES
Example 1 The First Coating Seed Pancreatin powder 300 g Coating Solution HPMC 2208 15 g Water I 300 ml Polyethyleneglycol 6000 ~ 2 g The Second Coatine Seed The first fine coated granule 300 g Coating Solution ~ Eudragit~ L 30D ( 1,320 ml (water dispersive) (400 g as solid powder) Water ~ 500 ml I I Propyleneglycol I 40 g (A) Preparation of the first fine coated granules While the pancreatin powder was floated in the fluid bed (SFC-MINI), it was sprayed with the above first coating solution. The product in the fluid bed was adjusted to a temperature of from 25°C to 60°C.
(B) Preparation of the second coated granules While the first fine coated granules were floated in the fluid bed, they were sprayed with the above second coating solution comprising Euragit~ L 30D and a plasticizer. The granules in the fluid bed did not depart from a temperature range of 25 °C
to 60°C. As the second coating base, Kollicoat MAE 30 DP can be used instead.
Example 2 The First Coating Seed Pancreatin powder 300 g Coating Solution Sodium alginate 3 g Water 300 ml Glycerin 3 g The Second Coating Seed The first fine coated granule 300 g Coating Solution Zein-DP~ (corn protein extract) 150 g Shellac 30 g 80% ethanol 1,200 ml Propylene glycol 6 g Glycerin 12 g The first and second coated granules were prepared in the same manner as described in Example 1, but using the above ingredients.
Example 3 The First Coating Seed Pancreatin powder 300 g Coating Solution HPMC 2910 10 g Water 200 ml Glycerin 2 g The Second Coating Seed The first fine coated granule 300 g Coating Solution HPMCP 400 g 80% ethanol 4,000 ml Glycerin fatty acid ester 30 g The first and second coated granules were prepared in the same manner as described in Example 1, but using the above ingredients. HPC can be used instead as the first coating base.
Example 4 The First Coating Seed Pancreatin powder 300 g Coating Solution HPC 10 g Water 200 ml Glycerin 4 g The Second Coating Seed The first fine coated granule 300 g Coating Solution Polyvinylacetatephthalate 450 g Water 4,000 ml Propylene glycol 10 g The first and second coated granules were prepared in the same manner as described in Example 1, but using the above ingredients.
Example 5 Seed Pancreatin powder 300 g Coating Solution HPMCP 400 g 80% ethanol 4,000 ml Glycerine fatty acid ester 30 g The pancreatin was mono-layer coated in the same manner as described in Example 1, but using the above ingredients.
Example 6 Seed Pancreatin powder 300 g Coating Solution Eudragit~ L 30D 1,485 ml (450 g as solid powder) Water 300 ml Triethyl citrate 30 g The pancreatin was mono-layer coated in the same manner as described in Example 1, but using the above ingredients. If desired, Kollicoat 30 DP can be used instead of the above coating base. The preparation of the mono-layer coated granule by increasing the spray rate can prevent reduction of the enzyme titer by the coating solution.
Experimental Example 1 The particle size distribution of the coated granules prepared by Examples 1 through 8 was determined. The results are indicated in Table 1 below.

Table 1. The Particle Size Distribution (%) of the Coated Pancreatin Granule Mesh Size (mm) 20 (0.84) 30 (0.59) 40 (0.42) 50 (0.297) Example 1 7.4 50.5 38.6 3.5 Example 2 9.5 47.6 34.4 8.5 Example 3 9.3 45.8 37.3 7.6 Example 4 11.7 44.1 40.0 4.2 Example 5 4.8 52.2 38.6 4.4 Example 6 9.0 54.7 30.5 5.8 It can be seen from Table 1 that particles of 30 to 40 meshes account for at least 80% of the coated granules. The results indicate that the coated granules prepared by the present invention are uniform.
Experimental Example 2 The coated pancreatin granules prepared by the above Examples 1 to 6 were measured on the activities of lipase, amylase and protease by the pancreatin assay described in the European Pharmacopoeia. The activities were compared to those of the raw pancreatin as control. The results are indicated in Table 2 below.
Table 2 The amount Enzyme activity of (U/mg) pancreatin in the coated Lipase Amylase Protease granule(%) Raw material 73.1 80.5 6.1 Example 38.4 28.3 31.5 2.4 Example 59.1 43.3 47.0 3.6 Example 39.5 28.9 32.0 2.4 Example 37.7 27.4 30.9 2.3 Example 41.1 30.3 33.8 2.6 Example 38.5 28.2 31.3 2.3 _g_ It can be seen from Table 2 that the enzyme titer of the coated pancreatin prepared by the above Examples 1 to 6 is almost consistent with that of the raw pancreatin as control in which the coating base and plasticizer were excluded. The results indicate that the enzyme titer of the pancreatin does not decrease during coating.
Experimental Example 3 From the coated granules prepared by Examples 1 to 6, two were selected depending on mesh size and compressed to obtain tablets. The dissolution test on the obtained tablets was carried out to determine the effect of the tableting pressure on various mesh size coated granules. Microcrystalline cellulose was used as an adjuvant and the amount of the coated granules was 50% by weight of the tablet. Each 800 ml of artificially prepared gastric fluids of pH 2.0 and pH 3.0 was stirred at 100 rpm in Dissolution Test Instrument 1 for 60 minutes. This was transferred to artificially prepared enteric fluid (phosphate buffer, pH 6.0) and was stirred at 100 rpm in Dissolution Test Instrument 2 for 30 minutes. The specimens taken in the proper quantity was tested on lipase activity. The results are indicated in Table below 3.
Table 3 Artificially Artificially produced produced gastric gastric fluid fluid of pH of pH
2.0 3.0 Lipase ToleranceLipase Tolerance activity (%) activity (%) (U/mg) (U/mg) 20-30 mesh23.8 84.1 26.1 92.2 E
l xamp e 30-40 mesh24.7 87.3 27.4 96.8 20-30 mesh15.0 34.6 18.5 42.7 E
l xamp e 30-40 mesh18.0 41.6 19.1 44.1 20-30 mesh24.1 83.4 26.5 91.7 E
l xamp e 30-40 mesh25.0 86.5 27.5 95.2 20-30 mesh23.2 84.7 24.5 89.4 E
l xamp 30-40 mesh24.5 89.4 26.2 95.6 e 20-30 mesh24.9 82.2 27.2 89.8 E
l 5 xamp 30-40 mesh26.5 87.5 28.7 94.7 e 20-30 mesh22.8 80.9 25.1 89.0 E
l xamp 30-40 mesh24.8 87.9 26.8 95.0 e The results of Table 3 indicate that the enteric coated pancreatin granule sufficiently serves as a protective barrier under acidic conditions depending on the mesh size of the granule.
The coating layer of the enteric coated pancreatin granule of the present invention was not broken by the tableting pressure. The acid tolerance test revealed that the larger the coated granule, the more the enzyme titer is reduced. This means that as the smaller coated granule is more able to dissipate or adsorb the tableting pressure, its coating layer is not broken.
Experimental Example 4 The coated pancreatin granules were compressed using the microcrystalline cellulose as an adjuvant. The dissolution test on the resulting tablet was carried out to decide the effect of the adjuvant on the tablet. The coated pancreatin granules of 30 to 40 mesh were used in amounts of 25%, 50%, 75% and 90% by weight based on the tablet.
The absolute amounts of the coated pancreatin granules in the tablets were same. The results are indicated in Table 4 below.

Table 4 Artificiallyproduced Artificiallyproduced gastric d of pH gastric of pH 3.0 flui 2.0 fluid The amount Lipase ToleranceLipase Tolerance of the coatedactivity (%) activity (%) pancreatin (U/mg) (U/mg) granule (%) 25 26.1 92.2 27.9 98.6 50 24.7 87.3 27.4 96.8 l Examp 75 21.2 74.9 24.4 86.2 e 90 18.3 64.7 21.0 74.2 25 20.4 47.1 21.3 49.2 50 18.0 41.6 19.1 44.1 l Examp 75 14.2 32.8 16.7 38.6 e 90 10.5 24.2 13.5 31.2 25 26.8 92.7 28.2 97.6 50 25.0 86.5 27.5 95.2 l Examp 75 22.7 78.5 25.1 86.9 e 90 19.4 67.1 21.0 72.7 25 26.0 94.9 27.0 98.5 50 24.5 89.4 26.2 95.6 l Examp 75 21.7 79.2 23.9 87.2 e 90 19.2 70.1 20.7 75.5 25 28.6 94.4 29.3 96.7 50 26.5 87.5 28.7 94.7 l E

xamp 75 23.2 76.6 26.4 87.1 e 90 20.0 66.0 23.1 76.2 25 26.9 95.4 27.9 98.9 SO 24.8 87.9 26.8 95.0 E
l xamp 75 21.5 76.2 24.0 85.1 e 90 18.7 66.3 21.2 75.2 The results of Table 4 indicate that when the adjuvant in the tablet is used in too small amounts, it cannot serve as a buffer against the tabletting pressure and the coating layer can be easily broken.

Claims (11)

1. A process for producing enteric coated pancreatin granules which comprises spraying the pancreatin powder with a coating solution at a high speed while floating the pancreatin powder at a low temperature to obtain the coated pancreatin granules.
2. The process according to claim 1 wherein the resulting coated pancreatin granules are again sprayed with another coating solution, identical to or different from the first coating solution, at a high speed while floating the granules at a low temperature.
3. The process according to claims 1 or 2 wherein the coating base is selected from a group consisting of corn protein extract, sodium alginate, alginic acid, methacrylic acid-ethyl methacrylate copolymer, shellac, carbopol, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, hydroxypropylmethyl acetate succinate, carboxymethylcellulose, cellulose acetate phthalate, hydroxypropylcellulose, ethylcellulose, methylcellulose, polyvinyl acetate phthalate, soybean protein, wheat protein, chitin, chitinic acid, agar, carrageenan, pectin, guar gum, locust bean gum, xanthan gum, gellan gum, arabic gum, and medium chain fatty acid of 6 to 12 carbons.
4. The process according to claims 1 or 2 wherein the plasticizer is selected from a group consisting of polyethylene glycol, glycerin fatty acid ester, sorvitan fatty acid ester, propylene glycol, glycerin, triethyl citrate, triacetin, cetyl alcohol, stearyl alcohol, and mixture thereof.
5. The process according to claims 1 or 2 wherein the plasticizer is used in amounts ranging from 1 % to 50% based on the total weight of the pancreatin used.
6. The process according to claims 1 or 2 wherein the pancreatin is used in amounts ranging from 1% to 95% based on the total weight of the granule.
7. The process according to claims 1 or 2 wherein the coating base is used in amounts ranging from 1% to 250% based on the total weight of the pancreatin used.
8. The process according to claims 1 or 2 wherein the solvent is selected from a group consisting of water, alcohol, acetone, acetonitrile, methylene chloride, ether, hexane, chloroform, 1,4-dioxane, tetrahydrofuran, dimethyl sulfoxide, ethyl acetate, methyl acetate and mixtures thereof.
9. The process according to claims 1 or 2 wherein the whole procedure is conducted at temperatures of 20°C to 70°C.
10. The process according to claims 1 or 2 wherein a fluid bed coater or CF-Granulator are used.
11. A process for producing a pancreatin tablet which comprises mixing, based on the total weight of the tablet, from 5% to 80% of enteric coated granules of claims 1 or 2 with a pharmaceutically acceptable adjuvant and tabletting the resulting mixture.
CA002263703A 1998-02-26 1999-02-26 A process for producing enteric coated pancreatin granules Abandoned CA2263703A1 (en)

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KR1998-6064 1998-02-26

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DE (1) DE19907764A1 (en)

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WO2012169997A1 (en) 2010-01-15 2012-12-13 Kemin Industries, Inc. Protected alpha-amylase
EP2616048A1 (en) * 2010-11-19 2013-07-24 Curemark, Llc Preparation and use of combination enzyme and gastrointestinal modulator delivery systems
US8778335B2 (en) 2000-08-14 2014-07-15 Curemark, Llc Methods of treating and diagnosing Parkinson's disease and related dysautonomic disorders
US8802087B2 (en) 2004-03-22 2014-08-12 Abbott Products Gmbh Pharmaceutical compositions of lipase-containing products, in particular of pancreation
US8815233B2 (en) 1999-12-17 2014-08-26 Curemark Llc Method for treating pervasive development disorders
US8921054B2 (en) 2000-11-16 2014-12-30 Curemark, Llc Methods for diagnosing pervasive development disorders, dysautonomia and other neurological conditions
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