CN115400097A - Aceclofenac enteric-coated microcapsule and preparation method thereof - Google Patents
Aceclofenac enteric-coated microcapsule and preparation method thereof Download PDFInfo
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- CN115400097A CN115400097A CN202110582930.2A CN202110582930A CN115400097A CN 115400097 A CN115400097 A CN 115400097A CN 202110582930 A CN202110582930 A CN 202110582930A CN 115400097 A CN115400097 A CN 115400097A
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- aceclofenac
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- coating
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- MNIPYSSQXLZQLJ-UHFFFAOYSA-N Biofenac Chemical compound OC(=O)COC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl MNIPYSSQXLZQLJ-UHFFFAOYSA-N 0.000 title claims abstract description 62
- 229960004420 aceclofenac Drugs 0.000 title claims abstract description 62
- 239000003094 microcapsule Substances 0.000 title claims abstract description 57
- 238000002360 preparation method Methods 0.000 title claims abstract description 34
- 239000011162 core material Substances 0.000 claims abstract description 53
- 239000000463 material Substances 0.000 claims abstract description 36
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 14
- 239000006187 pill Substances 0.000 claims abstract description 14
- 239000004014 plasticizer Substances 0.000 claims abstract description 14
- 239000011247 coating layer Substances 0.000 claims abstract description 12
- 239000000853 adhesive Substances 0.000 claims abstract description 11
- 230000001070 adhesive effect Effects 0.000 claims abstract description 11
- 239000002702 enteric coating Substances 0.000 claims abstract description 11
- 238000009505 enteric coating Methods 0.000 claims abstract description 11
- 239000011248 coating agent Substances 0.000 claims description 56
- 238000000576 coating method Methods 0.000 claims description 56
- 239000000243 solution Substances 0.000 claims description 50
- 238000005507 spraying Methods 0.000 claims description 41
- 239000007788 liquid Substances 0.000 claims description 37
- 239000002775 capsule Substances 0.000 claims description 30
- 238000003756 stirring Methods 0.000 claims description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 238000005086 pumping Methods 0.000 claims description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 14
- 230000032683 aging Effects 0.000 claims description 12
- 239000008188 pellet Substances 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical group CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 10
- 239000001856 Ethyl cellulose Substances 0.000 claims description 9
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 241000416162 Astragalus gummifer Species 0.000 claims description 8
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 8
- 229920001615 Tragacanth Polymers 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 8
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 8
- 229920001249 ethyl cellulose Polymers 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 8
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 8
- 229940069328 povidone Drugs 0.000 claims description 8
- 239000008213 purified water Substances 0.000 claims description 8
- 235000010487 tragacanth Nutrition 0.000 claims description 8
- 239000000196 tragacanth Substances 0.000 claims description 8
- 229940116362 tragacanth Drugs 0.000 claims description 8
- 239000006185 dispersion Substances 0.000 claims description 7
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 6
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 6
- 239000000377 silicon dioxide Substances 0.000 claims description 6
- 239000003826 tablet Substances 0.000 claims description 6
- 239000011230 binding agent Substances 0.000 claims description 5
- 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 claims description 5
- 235000013773 glyceryl triacetate Nutrition 0.000 claims description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 5
- 229960002622 triacetin Drugs 0.000 claims description 5
- 229920002472 Starch Polymers 0.000 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 4
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 235000012239 silicon dioxide Nutrition 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- 239000005720 sucrose Substances 0.000 claims description 4
- 239000000443 aerosol Substances 0.000 claims description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 3
- 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 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 3
- -1 patches Substances 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- 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 2
- 239000004925 Acrylic resin Substances 0.000 claims description 2
- 229920000178 Acrylic resin Polymers 0.000 claims description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 229940117841 methacrylic acid copolymer Drugs 0.000 claims description 2
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 229960004667 ethyl cellulose Drugs 0.000 claims 4
- 229940032147 starch Drugs 0.000 claims 2
- 229960004793 sucrose Drugs 0.000 claims 2
- 238000009472 formulation Methods 0.000 claims 1
- 239000001087 glyceryl triacetate Substances 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- 229960001855 mannitol Drugs 0.000 claims 1
- 229960002900 methylcellulose Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 21
- 229940079593 drug Drugs 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 8
- 210000000813 small intestine Anatomy 0.000 abstract description 3
- 238000013268 sustained release Methods 0.000 abstract description 3
- 230000005923 long-lasting effect Effects 0.000 abstract description 2
- 230000007774 longterm Effects 0.000 abstract description 2
- 210000000214 mouth Anatomy 0.000 abstract description 2
- 210000002784 stomach Anatomy 0.000 abstract description 2
- 239000012730 sustained-release form Substances 0.000 abstract description 2
- 239000010410 layer Substances 0.000 description 13
- 239000007771 core particle Substances 0.000 description 12
- 238000005469 granulation Methods 0.000 description 12
- 230000003179 granulation Effects 0.000 description 12
- 239000012085 test solution Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 6
- 210000004051 gastric juice Anatomy 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000007865 diluting Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 238000005303 weighing Methods 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 4
- 238000005538 encapsulation Methods 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 238000012795 verification Methods 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 229960001259 diclofenac Drugs 0.000 description 2
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 2
- 239000012738 dissolution medium Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000012055 enteric layer Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000012088 reference solution Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 201000002661 Spondylitis Diseases 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 235000010944 ethyl methyl cellulose Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 229920003087 methylethyl cellulose Polymers 0.000 description 1
- 239000002103 nanocoating Substances 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 235000010956 sodium stearoyl-2-lactylate Nutrition 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- KNYAZNABVSEZDS-UHFFFAOYSA-M sodium;2-octadecanoyloxypropanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC(C)C([O-])=O KNYAZNABVSEZDS-UHFFFAOYSA-M 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000007939 sustained release tablet Substances 0.000 description 1
Images
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
- A61K9/50—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
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Inorganic Chemistry (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides an aceclofenac enteric microcapsule and a preparation method thereof, the microcapsule comprises a core material and a coating layer, the core material comprises a pill core, aceclofenac and an adhesive; the coating layer comprises an enteric coating material, a plasticizer and an anti-sticking agent. The preparation method has the advantages that the types and proportions of the adhesive and the enteric-coated material are screened and optimized, the preparation process parameters are optimized and controlled, the stability and the long-term stability of the aceclofenac sustained-release microcapsule are effectively improved, the release of the drug in the oral cavity and the stomach is blocked, the drug is directionally delivered to the small intestine to be slowly released, and the release effect is long-lasting.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to an aceclofenac enteric-coated microcapsule and a preparation method thereof.
Background
Aceclofenac (Aceclofenac) is a new oral potent NSAID first marketed in 1992 by Prodesfara, spain. Aceclofenac as non-steroidal anti-inflammatory drug can exert various pharmacological actions on the focus part, is mainly used for treating various rheumatic arthritis, rheumatoid arthritis, osteoarthritis and spondylitis, and can also be used for treating pain and fever caused by various diseases.
Microencapsulation is actually an encapsulation technique whereby microcapsules with encapsulated or semi-permeable capsule films are produced by encapsulating a liquid or solid with a material having film-forming properties. The substances in the capsule are isolated from the external environment, so that the capsule can be prevented from being influenced by the external environment and is stable. Can achieve the controlled release effect by proper means, and has wide application prospect in the technical fields of biology, medicine, agriculture and the like.
The existing aceclofenac dosage forms include: aceclofenac tablets, sustained-release tablets, enteric-coated capsules and the like. Although these techniques are relatively mature, they still have a number of disadvantages. For example, the tablet is influenced by various factors such as pressure and powder flowability when being compressed, and a lot of difficulties are brought to the later investigation of the optimal process. Coated tablets have poor sustained/controlled release stability due to difficulty in accurately controlling the coating thickness. The direct loading of enteric capsules is influenced by materials, so that capsule shells from different manufacturers are difficult to achieve uniform effect, and the reproducibility is poor. The aceclofenac enteric microcapsule is prepared by preparing the aceclofenac into the enteric microcapsule, and then further tabletting or encapsulating can effectively avoid the problems.
Chinese patent CN103961336A discloses an aceclofenac enteric-coated pellet capsule and a preparation method thereof, the aceclofenac enteric-coated pellet is prepared by filling the aceclofenac enteric-coated pellet in a capsule shell, the aceclofenac enteric-coated pellet consists of a blank pellet core and a coating layer wrapped outside the blank pellet core, and the aceclofenac enteric-coated pellet comprises a main medicine layer, an isolating layer and an enteric layer from inside to outside in sequence. The isolation layer is wrapped between the main medicine layer and the enteric layer, so that the preparation process is complicated although the stability of the medicine is ensured, and the isolation layer is wrapped in a centrifugal mode, so that the coverage uniformity cannot be ensured, and the enteric coated tablet is not suitable for industrial production.
Disclosure of Invention
The invention provides an aceclofenac enteric-coated microcapsule, which overcomes the defects of the prior art, selects a formula and a preparation process, obtains the aceclofenac enteric-coated microcapsule which can be positioned in the small intestine to release medicine directionally, reduces the irritation of the gastrointestinal tract, increases the curative effect of the medicine, improves the compliance of patients and has high stability, and is easy for industrial production.
The first purpose of the invention is to provide an aceclofenac enteric microcapsule, which comprises a core material and a coating layer, wherein the core material comprises a pill core, aceclofenac and a binding agent; the coating layer comprises an enteric coating material, a plasticizer and an anti-sticking agent.
Further, the capsule core comprises the following components in parts by weight: 20-50 parts of pill core, 40-100 parts of aceclofenac and 12-36 parts of adhesive; the coating layer comprises the following components in parts by weight: 10-40 parts of enteric coating material, 2-15 parts of plasticizer and 2-15 parts of anti-sticking agent.
Specifically, the pellet core comprises one or more of sucrose, starch, microcrystalline cellulose, mannitol, hydroxypropyl methylcellulose and silicon dioxide, preferably microcrystalline cellulose and silicon dioxide, and the weight ratio is 2.
Specifically, the binder is selected from one or more of starch, sucrose, povidone, methyl cellulose, ethyl cellulose and tragacanth, preferably tragacanth and povidone, and the weight ratio is 1:1-3.
Specifically, the enteric coating material is selected from one or more of ethyl cellulose aqueous dispersion, acryl-EZE 93A, methacrylic acid copolymer and acrylic resin, preferably the ethyl cellulose aqueous dispersion and Acryl-EZE 93A, and the weight ratio is 1.
Specifically, the plasticizer is glycerol triacetate or diethyl phthalate; the anti-sticking agent is selected from one or more of talcum powder, superfine silica gel powder, magnesium stearate and sodium alginate.
Further, the capsule core comprises the following components in parts by weight:
20-50 parts of pill core
40-100 parts by weight of aceclofenac
12-36 parts of tragacanth and povidone
The coating layer comprises the following components in parts by weight:
ethyl cellulose water dispersion and Acryl-EZE 93A 10-40 weight parts
2-15 parts of glycerol triacetate
2-15 parts of talcum powder
Preferably, the first and second liquid crystal materials are,
30 parts by weight of microcrystalline cellulose-silicon dioxide pellet core
60 parts by weight of aceclofenac
Tragacanth and povidone 24 weight portions
The coating layer comprises the following components in parts by weight:
aqueous ethylcellulose dispersion and Acryl-EZE 93A 25 parts by weight
Glycerol triacetate 3 parts by weight
3 parts of talcum powder
The second object of the present invention is to provide the use of the aceclofenac enteric-coated microcapsules in the preparation of a preparation containing aceclofenac, which can be used as a preparation intermediate, and can be further processed into various preparations; the preparation forms comprise tablets, capsules, injections, patches, aerosols and suspensions.
A third object of the present invention is to provide a method for preparing aceclofenac enteric microcapsules, which is characterized by comprising the steps of:
(1) Preparing a capsule core material: dissolving aceclofenac in appropriate amount of solvent under stirring, adding binder under stirring to obtain solution, pumping into fluidized bed, and spraying onto the pellet core to obtain core material;
(2) Coating: adding a proper amount of purified water into the plasticizer and the anti-sticking agent, uniformly mixing, adding the enteric coating material, stirring to prepare a coating solution with the solid content of 18-22%, and pumping the coating solution into a fluidized bed for fluidized coating;
(3) Drying and aging to obtain the final product microcapsule.
Specifically, the solvent in the step (1) is selected from one or more of water, ethanol and propylene glycol; the air inlet temperature is 35-40 ℃, the material temperature is 30-36 ℃, the liquid spraying speed is 1.5-2.5ml/min, the liquid spraying pressure is 0.2-0.4MPa, the fan frequency is 15-18HZ, and the air inlet quantity is 28-32m 3 /h；
The stirring time of the step (2) is 20-40min, the air inlet temperature is 30-36 ℃, the material temperature is 28-33 ℃, the liquid spraying speed is 1.0-2.0ml/min, and the liquid spraying pressure is 0.15-0.35MPa, 14-17HZ of fan frequency and 28-32m of air inlet quantity 3 /h；
The aging temperature of the step (3) is 35-45 ℃, and the aging time is 5-9h.
The invention has the beneficial effects that:
1) Screening and optimizing the types and the proportion of the adhesive, selecting and using the tragacanth and the povidone according to the weight ratio of 1:1-3 times, the effect is optimal, and the stability and long-term stability of the aceclofenac sustained-release microcapsule can be effectively improved.
2) The type and the proportion of the enteric-coated materials are selected to block the release of the medicine in the oral cavity and the stomach, and the medicine is directionally delivered to the small intestine to be slowly released, so that the release effect is long-lasting.
3) The granular drug-containing particles in a spherical or nearly spherical shape are prepared by adopting a fluidized bed, and are further coated with enteric coating to prepare the aceclofenac enteric-coated microcapsule, the process parameters are controlled, and the uniformity and the drug loading rate of the enteric coating film of the microcapsule are improved.
Drawings
FIG. 1 is a graph showing the in vitro cumulative amount of drug released in examples 1 to 5
FIG. 2 is a graph showing the in vitro cumulative drug release of comparative examples 1 to 4
Detailed Description
In order to make the purpose and technical solution of the present invention more clear, the present invention is further described with reference to the following examples, but the scope of the present invention is not limited to these examples, and the examples are only used for explaining the present invention. It will be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the true scope of the invention. The present invention will be further described with reference to the following examples, but the present invention is not limited to these examples.
Example 1:
the prescription comprises the following components (unit: g):
the preparation method comprises the following steps:
(1) Microcapsule corePreparation of the compound (I): putting the pill core into Uster type (Wurster) fluidized bed granulation coating equipment as a core particle for granulation; stirring and dissolving aceclofenac and 80% ethanol, adding a formula amount of adhesive, stirring and dissolving, pumping the prepared solution into a fluidized bed, and spraying the solution onto core particles to prepare a capsule core material with smooth and round surface; the air inlet temperature is 38 ℃, the material temperature is 34 ℃, the liquid spraying speed is 2.0ml/min, the liquid spraying pressure is 0.3MPa, the fan frequency is 16HZ, and the air inlet volume is 30m 3 /h。
(2) Preparing an enteric-coated layer coating solution: adding plasticizer and antisticking agent into appropriate amount of purified water, mixing, adding enteric-coated polymer coating material, stirring for 30min to obtain coating solution with solid content of 20%.
(3) Coating: pumping the capsule core material into a fluidized bed in the step (1), and performing fluidized coating by using the coating solution prepared in the step (2), wherein the coating weight is increased by 5%; the air inlet temperature is 34 ℃, the material temperature is 30 ℃, the liquid spraying speed is 1.5ml/min, the liquid spraying pressure is 0.25MPa, the fan frequency is 16HZ, and the air inlet quantity is 30m 3 /h。
(4) And continuously aging the prepared microcapsule in a drying oven at 40 ℃ for 7h to obtain the finished microcapsule.
Example 2:
the prescription comprises the following components (unit: g):
the preparation method comprises the following steps:
(1) Preparation of microcapsule core: putting the pill core into Uster type (Wurster) fluidized bed granulation coating equipment as a core particle for granulation; stirring and dissolving aceclofenac and 80% ethanol, adding a formula amount of adhesive, stirring and dissolving, pumping the prepared solution into a fluidized bed, and spraying the solution onto core particles to prepare a capsule core material with smooth and round surface; the air inlet temperature is 35 ℃, the material temperature is 30 ℃, the liquid spraying speed is 1.5ml/min, the liquid spraying pressure is 0.2MPa, the fan frequency is 15HZ, and the air inlet quantity is 28m 3 /h。
(2) Preparing an enteric-coated layer coating solution: adding plasticizer and antisticking agent into appropriate amount of purified water, mixing, adding enteric-coated polymer coating material, stirring for 30min to obtain coating solution with solid content of 20%.
(3) Coating: pumping the capsule core material into a fluidized bed in the step (1), and carrying out fluidized coating on the coating solution prepared in the step (2), wherein the coating weight is increased by 5%; the air inlet temperature is 30 ℃, the material temperature is 28 ℃, the liquid spraying speed is 1.0ml/min, the liquid spraying pressure is 0.15MPa, the fan frequency is 14HZ, and the air inlet volume is 28m 3 /h。
(4) And continuously aging the prepared microcapsule in a drying oven at 35 ℃ for 9h to obtain the finished microcapsule.
Example 3:
the prescription comprises the following components (unit: g):
the preparation method comprises the following steps:
(1) Preparation of microcapsule core: putting the pill cores into a Wurster type (Wurster) fluidized bed granulation coating device to be used as core particles for granulation; stirring and dissolving aceclofenac and 80% ethanol, adding a formula amount of adhesive, stirring and dissolving, pumping the prepared solution into a fluidized bed, and spraying the solution onto core particles to prepare a capsule core material with smooth and round surface; the air inlet temperature is 40 ℃, the material temperature is 36 ℃, the liquid spraying speed is 2.5ml/min, the liquid spraying pressure is 0.4MPa, the fan frequency is 18HZ, and the air inlet quantity is 32m 3 /h。
(2) Preparing an enteric-coated layer coating solution: adding plasticizer and antisticking agent into appropriate amount of purified water, mixing, adding enteric-coated polymer coating material, stirring for 30min to obtain coating solution with solid content of 20%.
(3) Coating: pumping the capsule core material into a fluidized bed in the step (1), and carrying out fluidized coating on the coating solution prepared in the step (2), wherein the coating weight is increased by 5%; the air inlet temperature is 36 ℃, the material temperature is 33 ℃, the liquid spraying speed is 2.0ml/min, the liquid spraying pressure is 0.35MPa, the fan frequency is 17HZ, and the air inlet quantity is 32m 3 /h。
(4) And continuously aging the prepared microcapsule in a drying oven at 45 ℃ for 7h to obtain the finished microcapsule.
Example 4:
the formula comprises the following components (unit: g):
the preparation method comprises the following steps:
(1) Preparation of microcapsule core: putting the pill core into Uster type (Wurster) fluidized bed granulation coating equipment as a core particle for granulation; stirring and dissolving aceclofenac and 80% ethanol, adding a prescribed amount of adhesive, stirring and dissolving, pumping the prepared solution into a fluidized bed, and spraying the solution onto core particles to prepare a capsule core substance with smooth and round surface; the air inlet temperature is 38 ℃, the material temperature is 34 ℃, the liquid spraying speed is 2.0ml/min, the liquid spraying pressure is 0.3MPa, the fan frequency is 16HZ, and the air inlet quantity is 30m 3 /h。
(2) Preparing an enteric-coated layer coating solution: adding plasticizer and antisticking agent into appropriate amount of purified water, mixing, adding enteric-coated polymer coating material, stirring for 30min to obtain coating solution with solid content of 20%.
(3) Coating: pumping the capsule core material into a fluidized bed in the step (1), and carrying out fluidized coating on the coating solution prepared in the step (2), wherein the coating weight is increased by 5%; the air inlet temperature is 34 ℃, the material temperature is 30 ℃, the liquid spraying speed is 1.5ml/min, the liquid spraying pressure is 0.25MPa, the fan frequency is 16HZ, and the air inlet volume is 30m 3 /h。
(4) And continuously aging the prepared microcapsule in a drying oven at 40 ℃ for 7h to obtain the finished microcapsule.
Example 5:
the prescription comprises the following components (unit: g):
the preparation method comprises the following steps:
(1) Preparation of microcapsule core: putting the pill core into Uster type (Wurster) fluidized bed granulation coating equipment as a core particle for granulation; dissolving aceclofenac in 80% ethanol under stirring, adding adhesive, stirring, and spraying the obtained solution into fluidized bedPreparing capsule core material with smooth and round surface on the core particle; the air inlet temperature is 38 ℃, the material temperature is 34 ℃, the liquid spraying speed is 2.0ml/min, the liquid spraying pressure is 0.3MPa, the fan frequency is 16HZ, and the air inlet quantity is 30m 3 /h。
(2) Preparing enteric-coated layer coating liquid: adding plasticizer and antisticking agent into purified water, mixing, adding enteric-coated polymer coating material, stirring for 30min, and making into coating solution with solid content of 20%.
(3) Coating: pumping the capsule core material into a fluidized bed in the step (1), and carrying out fluidized coating on the coating solution prepared in the step (2), wherein the coating weight is increased by 5%; the air inlet temperature is 34 ℃, the material temperature is 30 ℃, the liquid spraying speed is 1.5ml/min, the liquid spraying pressure is 0.25MPa, the fan frequency is 16HZ, and the air inlet volume is 30m 3 /h。
(4) And continuously aging the prepared microcapsule in a drying oven at 40 ℃ for 7h to obtain the finished microcapsule.
Comparative example 1
The formula comprises the following components (unit: g):
the preparation method comprises the following steps:
the preparation method is the same as that of example 1.
Comparative example 2:
the formula comprises the following components (unit: g):
the preparation method comprises the following steps:
the preparation method is the same as that of example 1.
Comparative example 3:
the formula comprises the following components (unit: g):
the preparation method comprises the following steps:
the preparation method is the same as that of example 1.
Comparative example 4:
the formula comprises the following components (unit: g):
the preparation method comprises the following steps:
(1) Preparation of the core: putting the sucrose-starch-microcrystalline cellulose pill cores into Uster type (Wurster) fluidized bed granulation coating equipment to be used as core particles for granulation; stirring and dissolving aceclofenac and 80% ethanol, adding microcrystalline cellulose, propylhydroxy-beta-cyclodextrin and sodium stearoyl lactate according to the formula amount, stirring and dissolving, pumping the prepared solution into a fluidized bed, and spraying the solution onto core particles to prepare a capsule core substance with a smooth and round surface; the air inlet temperature is 38 ℃, the material temperature is 34 ℃, the liquid spraying speed is 2.0ml/min, the liquid spraying pressure is 0.3MPa, the fan frequency is 16HZ, and the air inlet volume is 30m 3 /h。
(2) Preparing an isolation layer: dissolving the superfine silica gel powder and the hydroxypropyl methylcellulose E5 in an ethanol solution, pumping into a fluidized bed, and spraying to the capsule core to form an isolation layer;
(3) Preparing enteric-coated layer coating liquid: adding L30D-55, lecithin, sodium hydroxide and magnesium stearate into a proper amount of purified water, uniformly mixing, adding an enteric-coated high-molecular coating material, and stirring for 30min to prepare a coating solution with the solid content of 20%.
(4) Coating: pumping the capsule core material into a fluidized bed in the step (1), and performing fluidized coating by using the coating solution prepared in the step (2), wherein the coating weight is increased by 5%; the air inlet temperature is 34 ℃, the material temperature is 30 ℃, the liquid spraying speed is 1.5ml/min, the liquid spraying pressure is 0.25MPa, the fan frequency is 16HZ, and the air inlet quantity is 30m 3 /h。
(5) And continuously aging the prepared microcapsule in a drying oven at 40 ℃ for 7h to obtain the finished microcapsule.
Verification of the embodiments
The inventor should explain that only some experimental data of the verification examples are listed here, and other experiments on the effects of the verification examples can also prove that the technical solutions provided by the present invention are excellent in effect, which are not listed here.
1. Drug loading and encapsulation efficiency measurements
An appropriate amount of the prepared aceclofenac enteric-coated microcapsules were taken, and the content of aceclofenac in the microcapsules was measured by a content measurement method, and the results are shown in table 1. Encapsulation efficiency = encapsulated drug content in the microcapsule/total amount of drug encapsulated and not encapsulated in the microcapsule.
TABLE 1 encapsulation efficiency measurement results of each example
2. In vitro cumulative Release assay
Accurately weighing appropriate amount of aceclofenac microcapsule, placing in 750ml of 0.1mol/L HCl (pH1.2) artificial gastric juice at 37 deg.C, with stirring paddle rotation speed of 50rpm, respectively sampling for 1h, 1.5h, 2h, and detecting release degree;
taking a proper amount of the dissolution liquid from the test solution, filtering, and precisely taking a proper amount of the subsequent filtrate.
The reference solution is prepared by accurately weighing about 10mg of aceclofenac reference, dissolving in 10ml of methanol in a 100ml measuring flask, diluting with dissolution medium to scale, shaking, accurately weighing 5ml, placing in a 20ml measuring flask, diluting with 0.1mol/L hydrochloric acid solution to scale, and shaking.
250ml of 0.2mol/L sodium phosphate solution preheated to 37 +/-0.5 ℃ is immediately added into the solution after 2 hours under the dissolution amount in the artificial gastric juice, and the mixture is uniformly mixed (2 mol/L sodium hydroxide solution or 2mol/L hydrochloric acid solution is used for adjusting the pH value to 6.8 when necessary), the rotating speed is 50rpm, and the operation is carried out according to the method. The sampling time intervals are respectively: 0.5h, 1.0h, 2.0h, 3.0h, 4.0h, 5h and 6h.
Taking out appropriate amount of dissolution liquid from the test solution, filtering, and taking out the subsequent filtrate.
The control solution is prepared by precisely measuring 5ml of control stock solution under the dissolution amount of the artificial gastric juice, placing the control stock solution into a 20ml measuring flask, uniformly mixing the control stock solution with dissolution media (0.1 mol/L hydrochloric acid solution and 0.2mol/L sodium phosphate solution according to the proportion of 3.
The results are shown in Table 2 and Table 3, and figure 1 and figure 2 (in the figure, 0-2h indicates that the microcapsule is in artificial gastric juice, and 2.5-8h indicates that the microcapsule is in artificial intestinal juice).
Table 2 in vitro release test results of aceclofenac enteric-coated microcapsules in each example
Table 3 in vitro release test results of aceclofenac enteric-coated microcapsules of each comparative example
3. Detection of substances related to aceclofenac enteric microcapsules
The related substances were measured by high performance liquid chromatography (general rule 0512). Solvent: mobile phase a-mobile phase B (30. Test solution: taking about 50mg of the product, accurately weighing, placing in a 25ml measuring flask, adding a solvent to dissolve and dilute to a scale, and shaking up. Control solution: taking a proper amount of diclofenac sodium reference substance, precisely weighing, adding a solvent for dissolving, and quantitatively diluting to prepare a solution containing about 0.4mg of diclofenac in each 1 ml. Control solution: precisely measuring 2ml of the test solution, placing the test solution in a 10ml measuring flask, diluting the test solution to the scale with a solvent, shaking up, precisely measuring 1ml of the test solution, placing the test solution in a 100ml measuring flask, precisely adding 1ml of the reference solution, diluting the test solution to the scale with the solvent, and shaking up. Chromatographic conditions are as follows: octadecylsilane chemically bonded silica is used as a filling agent; gradient elution was performed using 0.112% (W/V) phosphoric acid solution (pH adjusted to 7.0 with sodium hydroxide test solution) as mobile phase a and acetonitrile-water (90; the detection wavelength is 275nm; the injection volume is 10. Mu.l. Calculated by peak area according to external standard method, the peak area of diclofenac can not exceed 0.2%, the peak area of other single impurity can not be larger than the peak area of aceclofenac in the control solution (0.2%), and the sum of the peak areas of other impurity can not be larger than 2.5 times (0.5%) of the peak area of aceclofenac in the control solution. (accelerated stability conditions: temperature 40 ℃ C., relative humidity: 75%. + -. 5%) the results are shown in Table 4.
TABLE 4 detection results of aceclofenac enteric microcapsule-related substances
The aceclofenac enteric-coated microcapsules prepared in each embodiment of the invention meet the requirements, are insoluble in gastric juice (pH = 1.2) and soluble in small intestinal juice (pH = 6.8), and hardly release the drug in the gastric juice for 2h, so that the drug is released in the small intestinal juice, and the irritation to the gastrointestinal tract is eliminated. Meanwhile, the medicine is slowly released, and the action time is prolonged. Can also be used as a medicine carrying system to be further used for preparing various dosage forms such as tablets, capsules, injections, patches, aerosols, suspensions and the like, has simple and stable process and is suitable for industrial production.
Claims (10)
1. The aceclofenac enteric microcapsule is characterized by comprising a core material and a coating layer, wherein the core material comprises a pill core, aceclofenac and an adhesive; the coating layer comprises an enteric coating material, a plasticizer and an anti-sticking agent.
2. The aceclofenac enteric microcapsule according to claim 1, wherein said core comprises, in parts by weight: 20-50 parts of pill core, 40-100 parts of aceclofenac and 12-36 parts of adhesive; the coating layer comprises the following components in parts by weight: 10-40 parts of enteric coating material, 2-15 parts of plasticizer and 2-15 parts of anti-sticking agent.
3. Aceclofenac enteric microcapsule according to claim 1, characterized in that the ingredients of said pellet core are selected from one or more of sucrose, starch, microcrystalline cellulose, mannitol, hydroxypropylmethylcellulose, silicon dioxide, preferably microcrystalline cellulose and silicon dioxide, in a ratio of 2 parts by weight to 1 part by weight.
4. Aceclofenac enteric-coated microcapsule according to claim 1, characterized in that said binder is selected from one or more of starch, sucrose, povidone, methyl cellulose, ethyl cellulose, tragacanth, preferably tragacanth and povidone, in a weight ratio of 1:1-3.
5. Aceclofenac enteric microcapsule according to claim 1, characterized in that said enteric coating material is selected from one or more of ethyl cellulose aqueous dispersion, acryl-EZE 93A, methacrylic acid copolymer, acrylic resin, preferably ethyl cellulose aqueous dispersion and Acryl-EZE 93A, in a weight ratio of 1.
6. The aceclofenac enteric microcapsule according to claim 1, wherein said plasticizer is triacetin or diethyl phthalate; the antisticking agent is selected from one or more of talcum powder, superfine silica gel powder, magnesium stearate and sodium alginate.
7. The aceclofenac enteric microcapsule according to claim 2, characterized in that said core comprises, in parts by weight:
20-50 parts of pill core
40-100 parts by weight of aceclofenac
12 to 36 portions of tragacanth and povidone
The coating layer comprises the following components in parts by weight:
aqueous ethylcellulose dispersion and Acryl-EZE 93A 10-40 parts by weight
2-15 parts of glycerol triacetate
2-15 parts of talcum powder.
8. Use of the aceclofenac enteric microcapsules according to any one of claims 1 to 7 for the preparation of a formulation containing aceclofenac; the preparation forms comprise tablets, capsules, injections, patches, aerosols and suspensions.
9. A method for preparing aceclofenac enteric microcapsules according to claim 1, comprising the steps of:
(1) Preparing a capsule core material: dissolving aceclofenac in appropriate amount of solvent under stirring, adding binder under stirring to obtain solution, pumping into fluidized bed, and spraying onto the pill core to obtain capsule core;
(2) Coating: adding a proper amount of purified water into the plasticizer and the anti-sticking agent, uniformly mixing, adding the enteric coating material, stirring to prepare a coating solution with the solid content of 18-22%, and pumping the coating solution into a fluidized bed to perform fluidized coating on the capsule core;
(3) Drying and aging to obtain the final product microcapsule.
10. The preparation method according to claim 9, wherein the solvent in the step (1) is one or more selected from water, ethanol, propylene glycol; the air inlet temperature is 35-40 ℃, the material temperature is 30-36 ℃, the liquid spraying speed is 1.5-2.5ml/min, the liquid spraying pressure is 0.2-0.4MPa, the fan frequency is 15-18HZ, and the air inlet quantity is 28-32m < 3 >/h; the stirring time of the step (2) is 20-40min, the air inlet temperature is 30-36 ℃, the material temperature is 28-33 ℃, the liquid spraying speed is 1.0-2.0ml/min, the liquid spraying pressure is 0.15-0.35MPa, the fan frequency is 14-17HZ, and the air inlet amount is 28-32m < 3 >/h; the aging temperature of the step (3) is 35-45 ℃, and the aging time is 5-9h.
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