CN114931560B - Preparation method of hydroxypropyl methylcellulose hollow capsule - Google Patents
Preparation method of hydroxypropyl methylcellulose hollow capsule Download PDFInfo
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- CN114931560B CN114931560B CN202210369809.6A CN202210369809A CN114931560B CN 114931560 B CN114931560 B CN 114931560B CN 202210369809 A CN202210369809 A CN 202210369809A CN 114931560 B CN114931560 B CN 114931560B
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- capsule
- hollow capsule
- gel
- suspending agent
- glue
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- 239000002775 capsule Substances 0.000 title claims abstract description 114
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 title claims abstract description 72
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 title claims abstract description 72
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 title claims abstract description 17
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000003292 glue Substances 0.000 claims abstract description 56
- 239000000375 suspending agent Substances 0.000 claims abstract description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 28
- 238000000034 method Methods 0.000 claims abstract description 23
- 238000001035 drying Methods 0.000 claims abstract description 15
- 238000001816 cooling Methods 0.000 claims abstract description 10
- 238000005520 cutting process Methods 0.000 claims abstract description 8
- 239000000843 powder Substances 0.000 claims abstract description 7
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 5
- 230000002496 gastric effect Effects 0.000 claims abstract description 5
- 239000007788 liquid Substances 0.000 claims description 19
- 238000007598 dipping method Methods 0.000 claims description 16
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 14
- 235000010413 sodium alginate Nutrition 0.000 claims description 14
- 239000000661 sodium alginate Substances 0.000 claims description 14
- 229940005550 sodium alginate Drugs 0.000 claims description 14
- 210000004051 gastric juice Anatomy 0.000 claims description 13
- 235000011389 fruit/vegetable juice Nutrition 0.000 claims description 12
- 230000000968 intestinal effect Effects 0.000 claims description 12
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 9
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 9
- 239000002002 slurry Substances 0.000 claims description 9
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 9
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 9
- 239000002313 adhesive film Substances 0.000 claims description 8
- 238000002844 melting Methods 0.000 claims description 8
- 230000008018 melting Effects 0.000 claims description 8
- 238000012805 post-processing Methods 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 claims description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 6
- 229920002472 Starch Polymers 0.000 claims description 6
- 238000007689 inspection Methods 0.000 claims description 6
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 6
- 229940068984 polyvinyl alcohol Drugs 0.000 claims description 6
- 239000008107 starch Substances 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- 229920001285 xanthan gum Polymers 0.000 claims description 6
- 235000010493 xanthan gum Nutrition 0.000 claims description 6
- 239000000230 xanthan gum Substances 0.000 claims description 6
- 229940082509 xanthan gum Drugs 0.000 claims description 6
- 210000001072 colon Anatomy 0.000 claims description 4
- 239000004925 Acrylic resin Substances 0.000 claims description 3
- 229920000178 Acrylic resin Polymers 0.000 claims description 3
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims description 3
- 239000004375 Dextrin Substances 0.000 claims description 3
- 229920001353 Dextrin Polymers 0.000 claims description 3
- 229920002907 Guar gum Polymers 0.000 claims description 3
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 3
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 3
- 229920002752 Konjac Polymers 0.000 claims description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 3
- 229920001100 Polydextrose Polymers 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 229920001800 Shellac Polymers 0.000 claims description 3
- 235000010407 ammonium alginate Nutrition 0.000 claims description 3
- 239000000728 ammonium alginate Substances 0.000 claims description 3
- KPGABFJTMYCRHJ-YZOKENDUSA-N ammonium alginate Chemical compound [NH4+].[NH4+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O KPGABFJTMYCRHJ-YZOKENDUSA-N 0.000 claims description 3
- 229920002301 cellulose acetate Polymers 0.000 claims description 3
- 229940081734 cellulose acetate phthalate Drugs 0.000 claims description 3
- 235000019425 dextrin Nutrition 0.000 claims description 3
- 235000010417 guar gum Nutrition 0.000 claims description 3
- 239000000665 guar gum Substances 0.000 claims description 3
- 229960002154 guar gum Drugs 0.000 claims description 3
- 239000001341 hydroxy propyl starch Substances 0.000 claims description 3
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 3
- 235000013828 hydroxypropyl starch Nutrition 0.000 claims description 3
- 239000000252 konjac Substances 0.000 claims description 3
- 235000019823 konjac gum Nutrition 0.000 claims description 3
- 230000000873 masking effect Effects 0.000 claims description 3
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 claims description 3
- 239000000049 pigment Substances 0.000 claims description 3
- 239000004014 plasticizer Substances 0.000 claims description 3
- 235000013856 polydextrose Nutrition 0.000 claims description 3
- 239000001259 polydextrose Substances 0.000 claims description 3
- 229940035035 polydextrose Drugs 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 235000010408 potassium alginate Nutrition 0.000 claims description 3
- 239000000737 potassium alginate Substances 0.000 claims description 3
- MZYRDLHIWXQJCQ-YZOKENDUSA-L potassium alginate Chemical compound [K+].[K+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O MZYRDLHIWXQJCQ-YZOKENDUSA-L 0.000 claims description 3
- 239000003755 preservative agent Substances 0.000 claims description 3
- 230000002335 preservative effect Effects 0.000 claims description 3
- 239000004208 shellac Substances 0.000 claims description 3
- 235000013874 shellac Nutrition 0.000 claims description 3
- 229940113147 shellac Drugs 0.000 claims description 3
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 claims description 3
- 125000005591 trimellitate group Chemical group 0.000 claims description 3
- 239000004615 ingredient Substances 0.000 claims 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 claims 1
- 240000007472 Leucaena leucocephala Species 0.000 claims 1
- 239000000499 gel Substances 0.000 abstract description 22
- 108010010803 Gelatin Proteins 0.000 abstract description 19
- 239000008273 gelatin Substances 0.000 abstract description 19
- 229920000159 gelatin Polymers 0.000 abstract description 19
- 235000019322 gelatine Nutrition 0.000 abstract description 19
- 235000011852 gelatine desserts Nutrition 0.000 abstract description 19
- 239000010410 layer Substances 0.000 abstract description 16
- 238000004090 dissolution Methods 0.000 abstract description 12
- 238000004519 manufacturing process Methods 0.000 abstract description 9
- 239000007888 film coating Substances 0.000 abstract description 5
- 238000009501 film coating Methods 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 4
- 235000011837 pasties Nutrition 0.000 abstract description 3
- 230000000112 colonic effect Effects 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 29
- 239000000463 material Substances 0.000 description 18
- 108010025899 gelatin film Proteins 0.000 description 8
- 238000001514 detection method Methods 0.000 description 6
- 239000007863 gel particle Substances 0.000 description 5
- 239000008213 purified water Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001879 gelation Methods 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 229920002148 Gellan gum Polymers 0.000 description 3
- 210000004211 gastric acid Anatomy 0.000 description 3
- 235000010492 gellan gum Nutrition 0.000 description 3
- 239000000216 gellan gum Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 238000010008 shearing Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000001248 thermal gelation Methods 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- ZNOZWUKQPJXOIG-XSBHQQIPSA-L [(2r,3s,4r,5r,6s)-6-[[(1r,3s,4r,5r,8s)-3,4-dihydroxy-2,6-dioxabicyclo[3.2.1]octan-8-yl]oxy]-4-[[(1r,3r,4r,5r,8s)-8-[(2s,3r,4r,5r,6r)-3,4-dihydroxy-6-(hydroxymethyl)-5-sulfonatooxyoxan-2-yl]oxy-4-hydroxy-2,6-dioxabicyclo[3.2.1]octan-3-yl]oxy]-5-hydroxy-2-( Chemical compound O[C@@H]1[C@@H](O)[C@@H](OS([O-])(=O)=O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H]2OC[C@H]1O[C@H](O[C@H]1[C@H]([C@@H](CO)O[C@@H](O[C@@H]3[C@@H]4OC[C@H]3O[C@H](O)[C@@H]4O)[C@@H]1O)OS([O-])(=O)=O)[C@@H]2O ZNOZWUKQPJXOIG-XSBHQQIPSA-L 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- -1 hydroxypropyl groups Chemical group 0.000 description 2
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 2
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- YIXJRHPUWRPCBB-UHFFFAOYSA-N magnesium nitrate Chemical compound [Mg+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O YIXJRHPUWRPCBB-UHFFFAOYSA-N 0.000 description 2
- 239000002861 polymer material Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000008719 thickening Effects 0.000 description 2
- SGHZXLIDFTYFHQ-UHFFFAOYSA-L Brilliant Blue Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 SGHZXLIDFTYFHQ-UHFFFAOYSA-L 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012790 adhesive layer Substances 0.000 description 1
- 241001148470 aerobic bacillus Species 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
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- 239000011248 coating agent Substances 0.000 description 1
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- 210000005224 forefinger Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 150000002340 glycosyl compounds Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000010030 laminating Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
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- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000012372 quality testing Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000003813 thumb Anatomy 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4816—Wall or shell material
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Abstract
The invention discloses a preparation method of hydroxypropyl methylcellulose hollow capsules, which comprises the following steps: dispersing suspending agent and HPMC powder in hot water according to certain mass parts to prepare pasty glue solution; and then inserting the capsule mould into the glue solution, taking out, turning over, cooling, drying, pulling out the shell, cutting, sleeving and inspecting quality to obtain the hollow capsule finished product. The method uses the same equipment and process flow as the traditional gelatin hollow capsule, does not use a gel agent, achieves the aim of cooling and forming on the surface of a mould by utilizing the thermal gel property of hydroxypropyl methyl cellulose, and utilizes the solubility of a suspending agent in an acid-base environment and repeatedly dip-in glue to form a film coating layer, so that the prepared hollow capsule realizes multiple functions of gastric dissolution, enteric dissolution and colonic dissolution, has stable disintegration performance, low production cost, and strong practicability and wide usability.
Description
Technical Field
The invention relates to a hollow capsule, in particular to a preparation method of a hydroxypropyl methylcellulose hollow capsule, and belongs to the technical field of medicines.
Background
In the century history of capsules, gelatin has been widely used in the fields of foods, medicines and health products because of its wide sources, stable physicochemical properties and excellent processability while maintaining the position of the main stream capsule material. The unique structural characteristics of gelatin molecules have, however, made them somewhat disadvantageous and inadequate for their use. For example, gelatin has a high water content and loss of water when stored in a low humidity environment can cause the capsules to become brittle and even rupture; the gelatin capsule is easy to crosslink with drugs containing aldehyde, reducing glycosyl compounds and the like to delay disintegration, so that the water solubility of the gelatin capsule shell is poor, and the disintegration of the hollow capsule and the dissolution of the capsule content are delayed; moreover, the "toxic capsule event" is rather a continuous question of the prospect of traditional gelatin empty capsules.
Therefore, replacing gelatin with vegetable gelatin is becoming a major material of hollow capsules, and more paid attention to by developers and related manufacturers, among a plurality of vegetable gelatin materials capable of replacing gelatin, hydroxypropyl methylcellulose (hereinafter abbreviated as HPMC) is one of the most promising materials due to its excellent film forming property, low water content, high toughness and high chemical stability.
HPMC has good film forming, dispersing, thickening, adhesion, water retention, protective colloid and other properties, is a safe edible raw material, is widely applied to the fields of medicines and foods, and has been accepted by pharmacopoeia of various countries as a common pharmaceutical auxiliary material. The HPMC is characterized in that methyl and hydroxypropyl groups are introduced into cellulose, so that the HPMC has unique hydration-dehydration characteristics, an aqueous solution of the HPMC has thermal gelation, namely, the heated solution is gelled, the solution is cooled and then is recovered to a solution state, and the temperature at the time of gel formation is the gelation temperature, so that the HPMC also has the characteristic of being insoluble in hot water above the gelation temperature, and the HPMC begins to be dissolved after the hot water is cooled. Commercial HPMC gelation temperatures are generally around 60 ℃, and are specifically related to the number of HPMC substituents, the solution ion environment, and the like.
At present, the existing preparation methods of empty capsules using HPMC as a main component are mainly divided into two types:
The first method is to use the same technological process and equipment as the traditional gelatin hollow capsule, namely, the HPMC and other components such as the gel are melted at high temperature, the gel is dipped in a mold and then taken out, under the action of the gel, the gel on the mold is turned over and cooled, then condensed and formed, and finally the final hollow capsule product is formed through the procedures of drying, shell pulling, sleeving and the like;
The second method is to use a mold different from the conventional gelatin hollow capsule production line, such as a mold capable of continuously rotating, a mold with a heating function, or a mold cap with a special design, so that the purpose of losing fluidity of the gelatin solution can be achieved without using a gelling agent after the mold is dipped.
For the first method, there is a disadvantage in that a gel such as gellan gum, carrageenan, etc. must be used, which increases the cost of the empty capsule; more importantly, the principle of gel is mainly that gel is formed by ionic initiation; therefore, if trace sodium ions, potassium ions, calcium ions and the like exist in the alimentary canal of the user of the empty capsule, the disintegration of the empty capsule is inevitably delayed;
For the second method, although the pure HPMC hollow capsule can be manufactured, most of drying and dehydration of the glue solution need to be completed on the surface of the mould to thoroughly lose fluidity and solidification forming, the process takes too long, the phenomenon of uneven glue solution on the surface of the mould is extremely easy to generate, and a production line special for producing the HPMC hollow capsule has to be newly built for the existing hollow capsule manufacturer.
Disclosure of Invention
In order to solve the defects in the prior art, the invention aims to provide the preparation method of the HPMC hollow capsule which effectively reduces the production cost, has stable disintegration performance and can realize multifunctional use.
In order to achieve the above object, the present invention adopts the following technical scheme:
the preparation method of the hydroxypropyl methylcellulose hollow capsule comprises the following steps:
s1, glue melting: dispersing suspending agent and HPMC powder in hot water according to certain mass portions, and stirring to prepare pasty glue solution;
s2, inserting the capsule mould into the glue solution, taking out, turning over, and cooling to obtain a gel-like shell;
S3, post-processing: sequentially drying, removing shell, cutting, sleeving, and quality testing to obtain hollow capsule.
The mass portion in the step S1 is as follows: 5-30 parts of HPMC, 0.5-10 parts of suspending agent and 60-90 parts of water; the temperature of the hot water is 70-90 ℃.
The preparation method further comprises auxiliary components, wherein the auxiliary components comprise pigment, masking agent, preservative and plasticizer, and the mass parts of the auxiliary components are not more than 10 parts.
The suspending agent is dissolved in gastric juice, and the prepared hollow capsule is a gastric-soluble capsule; the suspending agent comprises starch, water-soluble starch, hydroxypropyl starch, dextrin, polydextrose, xanthan gum, guar gum, konjac gum, acacia gum, hydroxyethyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, polyethylene oxide, polyethylene glycol and polyvinyl alcohol.
The suspending agent is dissolved in intestinal juice, is insoluble or slightly soluble in gastric juice, and the prepared hollow capsule is an enteric capsule; the suspending agent comprises sodium alginate, potassium alginate, ammonium alginate, shellac, sodium carboxymethyl cellulose, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, polyvinyl alcohol phthalate, cellulose acetate trimellitate and acrylic resin.
In the step S2, since HPMC has a thermal gelation property, i.e., HPMC is insoluble in hot water to form a slurry, when the slurry is cooled below the gel point temperature of HPMC, HPMC begins to dissolve to form a transparent solution, at this time, the viscosity of the solution increases sharply, and when the viscosity increases sufficiently to counteract the flow of the solution caused by gravity, the solution loses fluidity to form a gel-like shell, thereby achieving the purpose of molding the solution dipped on the surface of the mold.
According to the preparation method, the outer layer of the hollow capsule is also covered with the adhesive film layer, and the adhesive film layer is gastric soluble or enteric soluble.
Further, the preparation method of the adhesive film layer comprises the following steps:
And S22, drying the gel-like shell prepared in the step S2, placing the gel-like shell in a glue film liquid, dipping the gel, turning over, cooling, and performing post-treatment in the step S3.
Still further, the components of the adhesive film liquid comprise suspending agent and water.
Furthermore, when the empty capsule is an enteric-coated capsule, the components of the glue film liquid also comprise a gel, and the empty capsule prepared after film coating is suitable for the colon, namely the colon-type empty capsule.
The invention has the advantages that:
The preparation method of the hydroxypropyl methylcellulose hollow capsule provided by the invention does not need to use a gel, achieves the purpose of cooling and forming on the surface of a die by utilizing the thermal gel characteristic of the hydroxypropyl methylcellulose, is rapid and uniform in forming, and can realize the production of the HPMC hollow capsule with stable disintegration performance by using the existing production equipment and production procedures of the gelatin hollow capsule.
The invention further utilizes the solubility of the suspending agent in an acid-base environment, is mixed with HPMC, and is further combined with repeated glue dipping to form a film coating layer, so that the prepared hollow capsule can be divided into gastric-soluble type, enteric-soluble type and colonic-soluble type, various using functions of gastric-soluble type, enteric-soluble type and colonic-soluble type are realized, and the inner layer does not contain gel, so that the disintegrating performance of the product is stable: the HPMC hollow capsule does not contain an ion-initiated gel, and the main material of the hollow capsule has chemical inertness and does not react with the content or the main material of the hollow capsule to cause the change of the disintegration property. Taking the gastric-soluble HPMC hollow capsules as an example, both the suspending agent and HPMC can be rapidly dissolved in an aqueous (including acidic) environment and have sufficient chemical stability so that disintegration in the stomach does not occur with delay.
The invention does not use the gel with higher cost in the formula, and the cut leftover materials can be recycled after being crushed because the gel is not used, and the cost of raw materials of the hollow capsule is obviously reduced by selecting the suspending agent with low cost; in addition, the preparation method of the HPMC empty capsule provided by the invention is completely suitable for the existing traditional gelatin empty capsule production line, and the empty capsule production line special for HPMC does not need to be re-built.
Detailed Description
The present invention will be specifically described with reference to the following specific examples.
The preparation method of the hydroxypropyl methylcellulose hollow capsule comprises the following steps:
S1, glue melting: dispersing 0.5-10 parts of suspending agent and 5-30 parts of HPMC powder in hot water with the gelation temperature higher than HPMC, preferably 70-90 ℃, adding not more than 10 parts of auxiliary components including pigment, masking agent, preservative, plasticizer or other components capable of endowing the hollow capsule with special functions according to requirements, and stirring to prepare uniform and stable pasty glue solution;
s2, inserting the capsule mould below the glue solution, taking out, turning over one to three times, and cooling to obtain a gel-like shell;
because HPMC has the characteristic of thermal gelation, namely HPMC is insoluble in hot water to form slurry, when slurry glue solution is cooled to below the gel point temperature of HPMC, HPMC begins to dissolve to form transparent solution, the viscosity of the glue solution rises sharply at the moment, and when the viscosity rises enough to offset the glue solution flowing caused by gravity, the glue solution loses fluidity, so that the purpose of forming glue solution dipped on the surface of a die is achieved;
S22, film coating: drying the dried gel-like shell, placing the dried gel-like shell into a glue film liquid, dipping the glue, turning over and cooling;
s3, post-processing: the hollow capsule finished product is prepared by the process steps of drying, shell pulling, cutting, sleeving, quality inspection and the like which are completely consistent with those of the traditional gelatin hollow capsule.
The suspending agent is selected from starch, water-soluble starch, hydroxypropyl starch, dextrin, polydextrose, xanthan gum, guar gum, konjac gum, acacia gum, hydroxyethyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, polyethylene oxide, polyethylene glycol, polyvinyl alcohol, sodium alginate, potassium alginate, ammonium alginate, shellac, sodium carboxymethyl cellulose, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, polyvinyl alcohol phthalate, cellulose acetate trimellitate, and acrylic resin.
The suspending agent has the functions of thickening and stabilizing HPMC gel particles in hot water, assisting in film forming, reducing cost, adjusting disintegration speed and the like; the suspending agent is a hot water soluble or dispersible polymer material, and is dissolved or dispersed in hot water to form a viscous solution. Under the action of a certain shearing force, HPMC forms thermogel particles in hot water, and the larger the shearing force is, the longer the shearing force is applied, and the smaller the size of the thermogel particles of HPMC is, the more stable the thermogel particles of HPMC are. The suspending agent is coated on the outer layer of the HPMC thermal gel particles, and due to the coating effect and the viscosity effect of the suspending agent, the process of agglomerating and settling the HPMC thermal gel particles can be slowed down, the stability of the HPMC thermal gel particles is improved, and the viscosity of a viscous solution formed by the suspending agent is higher, so that the HPMC thermal gel particles are more stable. Meanwhile, the suspending agent is used as a hydrophilic polymer material, has film forming property, is blended with HPMC to form a wall material of the hollow capsule, and can play roles in assisting film forming and reducing the cost of the wall material. In addition, the dissolution speed of the suspending agent in water can also be adjusted, and the higher the dissolution speed of the suspending agent in water is, the higher the disintegration speed of the hollow capsule is.
According to the solubility of the suspending agent in gastric juice and intestinal juice with different pH values, different types of hollow capsules can be prepared by using different suspending agents: if the suspending agent is dissolved in gastric juice, the prepared hollow capsule is a gastric-soluble capsule; if the suspending agent is dissolved in intestinal juice and is insoluble or slightly soluble in gastric juice, the prepared hollow capsule is an enteric capsule.
The film layer is used as a film coating layer, and the solubility of the hollow capsule is regulated, so that the hollow capsule is suitable for gastric dissolution, enteric dissolution and further colonic dissolution.
Example 1
S1, glue melting: dispersing 0.1 g of xanthan gum and 30g of HPMC in 69.9 g of purified water at 70 ℃ and continuously stirring for 30 minutes at a low speed to form uniform and stable bubble-free slurry glue solution;
S2, dipping glue and overturning and forming a die: inserting the mold below the liquid level of the glue, dipping a certain amount of the glue, taking out, turning over once, and forming a transparent stable gel film on the surface of the mold by the glue;
S3, post-processing: drying, shell pulling, cutting, sleeving and quality inspection are carried out according to the procedures of the traditional gelatin hollow capsule, so as to obtain the transparent HPMC hollow capsule.
Because the xanthan gum is adopted as a suspending agent, and the xanthan gum can be dissolved in an acidic solution, the prepared empty capsule product is a gastric-soluble empty capsule.
Example 2
S1, glue melting: dispersing 3 g of sodium alginate, 5g of HPMC, 7 g of titanium dioxide and 1 g of brilliant blue in 84 g of purified water at 80 ℃, and continuously stirring for 30 minutes at a low speed to form uniform and stable bubble-free slurry glue solution;
S2, dipping glue and overturning and forming a die: inserting the mold below the liquid level of the glue, dipping a certain amount of the glue, taking out, turning over once, and forming a transparent stable gel film on the surface of the mold by the glue;
S3, post-processing: drying, shell pulling, cutting, sleeving and quality inspection are carried out according to the procedures of the traditional gelatin hollow capsule, so as to obtain the blue HPMC hollow capsule.
The enteric-coated sodium alginate is used as a suspending agent, so that the capsule wall material formed by the sodium alginate and the HPMC is not dissolved or disintegrated in gastric acid, but slowly dissolved in neutral intestinal juice, and the dissolution speed of the wall material in the intestinal juice can be accelerated by the HPMC, so that the obtained empty capsule is an enteric-coated empty capsule.
Example 3
S1, glue melting: dispersing 10g of low molecular weight sodium carboxymethyl cellulose and 8g of HPMC in 82 g of purified water at 90 ℃ and continuously stirring for 30 minutes at a low speed to form uniform, stable and bubble-free slurry glue solution;
s2, dipping glue and overturning and forming a die: inserting the mold below the liquid level of the glue, dipping a certain amount of the glue, taking out, turning over once, and forming a transparent stable gel film on the surface of the mold by the glue;
S22, laminating, which comprises the following substeps:
a1, drying: drying the gel film prepared in the step S2;
A2, glue melting again: 1g of sodium alginate is dissolved in 99 g of pure water at 60 ℃ to prepare a glue film liquid;
A3, repeatedly dipping in glue: inserting a mold with a dried gel film into the film liquid obtained in the step 4, dipping a small amount of film liquid, taking out, turning over for three times, and cooling;
Because the inner layer capsule wall material is a completely hydrophilic material, after repeated glue dipping, the moisture of the outer layer film liquid can diffuse into the inner layer dry gel film, the viscosity of the outer layer film liquid is lower, the film formed after glue dipping is thinner, the viscosity of the outer layer film liquid is gradually increased until the fluidity is lost while the outer layer film liquid is turned over and cooled, and therefore, the transparent stable gel film can be formed on the surface of a mold again without adding materials with gel effects such as HPMC (HPMC) and the like;
s3, post-processing: drying, shell pulling, cutting, sleeving and quality inspection are carried out according to the procedures of the traditional gelatin hollow capsule, so as to prepare the transparent hollow capsule.
Because the sodium carboxymethyl cellulose and the sodium alginate are enteric-coated materials, the formed hollow capsule cannot be dissolved or disintegrated in gastric acid, but in neutral intestinal juice, the sodium carboxymethyl cellulose and the sodium alginate begin to be slowly dissolved, and because the molecular weight of the sodium carboxymethyl cellulose is low and the outer sodium alginate adhesive layer is thinner, the formed hollow capsule can be disintegrated in neutral intestinal juice quickly, and therefore, the obtained hollow capsule is the enteric-coated hollow capsule.
Example 4
Step A2, glue is converted again: 3 g of sodium alginate, 0.1 g of gellan gum and 0.1 g of potassium chloride are dissolved in 96.8 g of purified water at 70 ℃ to prepare a glue film liquid;
the rest of the procedure was the same as in example 3, to prepare transparent hollow capsules.
Because sodium carboxymethyl cellulose and sodium alginate are enteric-coated materials, the formed hollow capsule can not be dissolved or disintegrated in gastric acid, but in neutral intestinal juice, sodium carboxymethyl cellulose and sodium alginate begin to be slowly dissolved, but because the viscosity of outer sodium alginate is higher, the formed adhesive film is thicker, and gellan gum is adopted as a gel agent, so that the dissolution of the formed hollow capsule in intestinal tracts is slower, the dissolution speed of the formed hollow capsule can be accelerated until the hollow capsule enters a weak alkaline environment of colon, the effect of colon positioning disintegration is achieved, and the obtained hollow capsule is ensured to be the colon-soluble hollow capsule from two aspects of disintegration time control and pH value dependence.
Example 5
S1, glue melting: the leftover material (hollow capsule) of the example 1 is crushed and dispersed in 69.9 g of purified water with the temperature of 70 ℃ for 30 minutes by continuous low-speed stirring to form uniform and stable bubble-free slurry glue solution;
S2, dipping glue and overturning and forming a die: inserting the mold below the liquid level of the glue, dipping a certain amount of the glue, taking out, turning over once, and forming a transparent stable gel film on the surface of the mold by the glue;
S3, post-processing: drying, shell pulling, cutting, sleeving and quality inspection are carried out according to the procedures of the traditional gelatin hollow capsule, so that the transparent HPMC hollow capsule is obtained and is a gastric soluble HPMC hollow capsule.
The present example demonstrates that the scrap of example 1 can be recycled without affecting the quality of the product.
According to the detection method of the gelatin hollow capsule and the enteric gelatin hollow capsule in the 2015 edition Chinese pharmacopoeia, partial indexes of the empty capsule samples prepared in the above embodiment are detected,
Detection standard:
appearance detection: the capsule body is smooth and clean, has uniform color, smooth cut, no deformation and no foreign odor, and is qualified.
And (5) tightness detection: taking 10 samples, lightly pinching two ends of the capsule by thumb and forefinger, rotating and pulling out the two ends, not having bonding, deformation or rupture, then filling talcum powder, sleeving and locking the cap and the body, and directly dropping the cap and the body on a template with the thickness of 2cm at the height of 1m one by one without powder leakage; if the powder leaks a little, the powder should not exceed 1 granule.
Friability detection: taking 50 samples, placing in a surface dish, placing in a dryer containing saturated solution of magnesium nitrate, keeping the temperature at 25+/-1 ℃ for 24 hours, taking out, immediately placing into glass tubes (24 mm in inner diameter and 200mm in length) standing on a wood plate (2 cm in thickness) one by one, freely dropping cylindrical weights (made of polytetrafluoroethylene, 22mm in diameter and 20+/-0.1 g in weight) from the mouth of the glass tube, and if the capsules are broken, not exceeding 5.
And (3) detecting disintegration time limit: taking 6 samples, filling talcum powder, and completely dissolving or disintegrating the gastric-soluble samples in artificial gastric juice within 10 minutes; the enteric-coated sample does not crack or disintegrate in the artificial gastric juice for 2 hours, and should disintegrate completely in the artificial gastric juice for 1 hour; the colon-soluble sample does not crack or disintegrate in artificial gastric juice for 2 hours or in artificial intestinal juice for 1 hour, and should disintegrate in artificial intestinal juice for 1 hour.
Microbial limit detection: the total number of aerobic bacteria in each 1g sample is not more than 1000cfu, the total number of mould and yeast is not more than 100cfu, and the escherichia coli cannot be detected; no salmonella could be detected per 10g of sample.
The test results are shown in table 1 below:
TABLE 1
The foregoing has shown and described the basic principles, principal features and advantages of the invention. It will be appreciated by persons skilled in the art that the above embodiments are not intended to limit the invention in any way, and that all technical solutions obtained by means of equivalent substitutions or equivalent transformations fall within the scope of the invention.
Claims (6)
1. The preparation method of the hydroxypropyl methylcellulose hollow capsule is characterized by comprising the following steps of:
S1, glue melting: dispersing 0.5-10 parts of suspending agent and 5-30 parts of HPMC powder in 60-90 parts of hot water with the temperature of 70-90 ℃ according to parts by weight, and stirring to prepare slurry glue solution;
s2, inserting the capsule mould into the glue solution, taking out, turning over, and cooling to obtain a gel-like shell;
s3, post-processing: sequentially drying, pulling out the shell, cutting, sleeving and quality inspection to obtain a hollow capsule finished product;
The suspending agent is dissolved in gastric juice, and the prepared hollow capsule is a gastric-soluble capsule;
The suspending agent is dissolved in intestinal juice, is insoluble or slightly soluble in gastric juice, and the prepared hollow capsule is an enteric capsule;
The suspending agent dissolved in gastric juice is one or more than two selected from starch, water-soluble starch, hydroxypropyl starch, dextrin, polydextrose, xanthan gum, guar gum, konjac gum, acacia, hydroxyethyl cellulose, polyvinylpyrrolidone, polyethylene oxide, polyethylene glycol and polyvinyl alcohol;
The suspending agent which is soluble in intestinal juice and is insoluble or slightly soluble in gastric juice is one or more than two selected from sodium alginate, potassium alginate, ammonium alginate, shellac, sodium carboxymethyl cellulose, cellulose acetate phthalate, polyvinyl alcohol phthalate, cellulose acetate trimellitate and acrylic resin.
2. The method for preparing the hydroxypropyl methylcellulose hollow capsule according to claim 1, further comprising an auxiliary ingredient, wherein the auxiliary ingredient is not more than 10 parts by mass, and comprises pigment, masking agent, preservative and plasticizer.
3. The method for preparing the hydroxypropyl methylcellulose hollow capsule according to any one of claims 1 to 2, wherein the outer layer of the hollow capsule is further covered with a film layer, and the film layer is gastric soluble or enteric soluble.
4. The method for preparing the hydroxypropyl methylcellulose hollow capsule according to claim 3, wherein the method for preparing the adhesive film layer is as follows:
And S22, drying the gel-like shell prepared in the step S2, placing the gel-like shell in a glue film liquid, dipping the gel, turning over, cooling, and performing post-treatment in the step S3.
5. The method for preparing hydroxypropyl methylcellulose hollow capsules according to claim 4, wherein the components of the adhesive film liquid comprise suspending agent and water.
6. The method according to claim 5, wherein when the hollow capsule is an enteric capsule, the components of the adhesive film liquid further comprise a gel, and the hollow capsule is suitable for colon.
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| JP2010202550A (en) * | 2009-03-02 | 2010-09-16 | Qualicaps Co Ltd | Enteric capsule |
| CN106924211A (en) * | 2017-01-18 | 2017-07-07 | 浙江万里学院 | A kind of enteric-coated hollow capsule and preparation method thereof |
| CN112546016A (en) * | 2020-12-15 | 2021-03-26 | 浙江万里学院 | Enteric hollow cellulose capsule and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2010202550A (en) * | 2009-03-02 | 2010-09-16 | Qualicaps Co Ltd | Enteric capsule |
| CN106924211A (en) * | 2017-01-18 | 2017-07-07 | 浙江万里学院 | A kind of enteric-coated hollow capsule and preparation method thereof |
| CN112546016A (en) * | 2020-12-15 | 2021-03-26 | 浙江万里学院 | Enteric hollow cellulose capsule and preparation method thereof |
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