CN101658501A - Minocycline hydroehloride sustained- release tablets and preparation method thereof - Google Patents
Minocycline hydroehloride sustained- release tablets and preparation method thereof Download PDFInfo
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- CN101658501A CN101658501A CN200810118869A CN200810118869A CN101658501A CN 101658501 A CN101658501 A CN 101658501A CN 200810118869 A CN200810118869 A CN 200810118869A CN 200810118869 A CN200810118869 A CN 200810118869A CN 101658501 A CN101658501 A CN 101658501A
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- cellulose
- minocycline hydrochloride
- coating material
- slow releasing
- coating
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- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title claims description 18
- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 title abstract 4
- 229960004023 minocycline Drugs 0.000 title abstract 4
- 239000011248 coating agent Substances 0.000 claims abstract description 31
- 238000000576 coating method Methods 0.000 claims abstract description 31
- 239000000463 material Substances 0.000 claims abstract description 24
- 239000000314 lubricant Substances 0.000 claims abstract description 13
- 239000000945 filler Substances 0.000 claims abstract description 9
- WTJXVDPDEQKTCV-UHFFFAOYSA-N 4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydron;chloride Chemical compound Cl.C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2C1CC1C(N(C)C)C(=O)C(C(N)=O)=C(O)C1(O)C2=O WTJXVDPDEQKTCV-UHFFFAOYSA-N 0.000 claims description 32
- 229960002421 minocycline hydrochloride Drugs 0.000 claims description 32
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 24
- 239000003826 tablet Substances 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 18
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 16
- 239000008187 granular material Substances 0.000 claims description 16
- 235000019359 magnesium stearate Nutrition 0.000 claims description 12
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
- 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 10
- 239000008101 lactose Substances 0.000 claims description 10
- 239000000741 silica gel Substances 0.000 claims description 10
- 229910002027 silica gel Inorganic materials 0.000 claims description 10
- 239000000853 adhesive Substances 0.000 claims description 8
- 230000001070 adhesive effect Effects 0.000 claims description 8
- -1 Hydroxypropyl Chemical group 0.000 claims description 6
- 229920002472 Starch Polymers 0.000 claims description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 6
- 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 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 6
- 239000008107 starch Substances 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 4
- 229920001747 Cellulose diacetate Polymers 0.000 claims description 4
- 239000001856 Ethyl cellulose Substances 0.000 claims description 4
- 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 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- 229920002301 cellulose acetate Polymers 0.000 claims description 4
- 238000007908 dry granulation Methods 0.000 claims description 4
- 229920001249 ethyl cellulose Polymers 0.000 claims description 4
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 4
- 229920000609 methyl cellulose Polymers 0.000 claims description 4
- 239000001923 methylcellulose Substances 0.000 claims description 4
- 235000010981 methylcellulose Nutrition 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- BAZVSMNPJJMILC-UHFFFAOYSA-N triadimenol Chemical compound C1=NC=NN1C(C(O)C(C)(C)C)OC1=CC=C(Cl)C=C1 BAZVSMNPJJMILC-UHFFFAOYSA-N 0.000 claims description 4
- 238000005303 weighing Methods 0.000 claims description 4
- 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
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims description 2
- 229920001661 Chitosan 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
- 229920001353 Dextrin Polymers 0.000 claims description 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 229920003091 Methocel™ Polymers 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- 229920000881 Modified starch Polymers 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 235000010980 cellulose Nutrition 0.000 claims description 2
- 229940081734 cellulose acetate phthalate Drugs 0.000 claims description 2
- 238000004132 cross linking Methods 0.000 claims description 2
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims description 2
- 239000006185 dispersion Substances 0.000 claims description 2
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 2
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 2
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 229960001855 mannitol Drugs 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 229940068984 polyvinyl alcohol Drugs 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 239000002002 slurry 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
- 229940032147 starch Drugs 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 239000004408 titanium dioxide Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 14
- 230000000694 effects Effects 0.000 abstract description 9
- 230000002045 lasting effect Effects 0.000 abstract description 2
- 239000011230 binding agent Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 8
- 239000004098 Tetracycline Substances 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 235000019364 tetracycline Nutrition 0.000 description 3
- 150000003522 tetracyclines Chemical class 0.000 description 3
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 230000002924 anti-infective effect Effects 0.000 description 2
- 229960005475 antiinfective agent Drugs 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229940072172 tetracycline antibiotic Drugs 0.000 description 2
- 229940040944 tetracyclines Drugs 0.000 description 2
- 210000001685 thyroid gland Anatomy 0.000 description 2
- 241000304886 Bacilli Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000606153 Chlamydia trachomatis Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 206010070840 Gastrointestinal tract irritation Diseases 0.000 description 1
- 206010018498 Goitre Diseases 0.000 description 1
- 206010018612 Gonorrhoea Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 241000202921 Ureaplasma urealyticum Species 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229940038705 chlamydia trachomatis Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 201000003872 goiter Diseases 0.000 description 1
- 208000001786 gonorrhea Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
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- 230000005923 long-lasting effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
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- 229930101283 tetracycline Natural products 0.000 description 1
- 208000013076 thyroid tumor Diseases 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention aims to provide minocycline hydroehloride sustained-release tablets with higher stability of medicament release and administrative safety, which are characterized by consisting of minocycline hydroehloride, a slow release material, a filler, a binder, a lubricating agent and a coating material. The minocycline hydroehloride sustained-release tablets have the characteristics of havingconvenient administration, lasting effect and stable curative effect, reducing untoward effect, improving the compliance of patients and the like.
Description
Technical field
The present invention relates to a kind of minocycline hydrochloride sustained release tablet and preparation method thereof, belong to field of medicaments.
Technical background
Minocycline hydrochloride is semi-synthetic Tetracyclines broad ectrum antibiotic, and tool is efficient and long-lasting, and in tetracycline antibiotics, the antibacterial action of this product is the strongest.Antimicrobial spectrum and tetracycline are close.Gram positive bacteria is comprised the staphylococcus aureus, streptococcus etc. of anti-tetracycline and the anti-plucked instrument bacterium of gonorrhea in the gram-negative bacteria all have very strong effect; To the effect of gram negative bacilli generally a little less than; This product also has good inhibitory effect to chlamydia trachomatis and ureaplasma urealyticum.Owing to abuse tetracycline antibiotics, existing most of common Grain-positives and negative bacterium are all to this product drug resistance in recent years.
The mechanism of action of minocycline hydrochloride is to combine with the A position of ribosome 30S subunit, stops the prolongation of peptide chain, thereby suppresses the protein synthesis of antibacterial or other pathogenic microorganisms.Minocycline hydrochloride is a bacteriostatic, but when high concentration, also has bactericidal action.
Minocycline hydrochloride can cause the thyroid of laboratory animal (rat, Canis familiaris L. and monkey) to become black.Rat gives this product and carries out chronic treatment, and the result causes goiter, even thyroid tumor.Minocycline hydrochloride also can cause the thyroid hypertrophy of rat and Canis familiaris L..
In recent years, it is 40,000,000,000 dollars that the average annual growth rate in antibiotic market, the world is about 8%, 1998 year world's anti-infectives market sales revenue, and last year, anti-infectives market sales revenue in the world's was 56,000,000,000 dollars.Tetracyclines accounts for 5%, 2.8 hundred million dollars of sales volumes.The raw material of minocycline hydrochloride is sold and is accounted for 60%, and its preparation sales volume is more than 1,500,000,000 dollars.Because its clinical application range is wide, has a broad antifungal spectrum, effect is strong.Therefore, minocycline hydrochloride has the huge market share, and along with the production domesticization of raw material, cost will descend, the raising that profit margin will be bigger.Therefore developing this product will obtain huge economic benefit, and social benefit.
Minocycline hydrochloride sustained release tablet has following advantage:
1, compare with conventional formulation, the slow releasing preparation rate of releasing drug is steady, near the zero level rate process, can overcome " peak valley " phenomenon that is produced behind the ordinary preparation multiple dose administration.After conventional formulation was taken medicine, drug level rose to maximum rapidly, because metabolism is drained and Degradation, reduced rapidly again then, drug level was controlled between minimum effective drug concentration and the maximum safe concentration relatively more difficult;
2, can make in the body effective blood drug concentration length of holding time, and steadily, utilization ratio of drug can reach 80～90%, and the utilization rate of conventional medicine only is 40～60%;
3, can reduce medicine to the gastrointestinal side effect.Conventional formulation is made controlled release preparation and can be reduced side effect because the disintegrate stripping rapidly in intestinal of oral back is big to GI irritation;
4, the oral obvious fluctuation of having avoided blood drug level of minocycline hydrochloride sustained release tablet has improved bioavailability.Easy to use, adverse reaction reduction, improved patient's compliance.
Summary of the invention
The purpose of this invention is to provide a kind of stability of medicine release and the higher minocycline hydrochloride sustained release tablet of safety of medication, have that convenient drug administration, effect are lasting, stable curative effect, adverse reaction reduction, characteristics such as patient's compliance of having improved.
Minocycline hydrochloride sustained release tablet of the present invention is characterized in that being made up of minocycline hydrochloride, slow-release material, filler, adhesive, lubricant, coating material.
Slow releasing tablet of the present invention, the minocycline hydrochloride effective dose is 10mg～1000mg, is preferably 100mg～400mg.
Slow releasing tablet of the present invention is characterized in that described slow-release material can select for use in hydroxypropyl methylcellulose, Sulisi aqueous dispersion, ethyl cellulose, methylcellulose, cellulose acetate-phthalate, hydroxypropyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl-cellulose, cellulose acetate, cellulose diacetate, Triafol T, glyceryl monostearate, the hydroxy methocel one or more to make.Preferred hydroxypropyl methylcellulose.
Slow releasing tablet of the present invention, it is characterized in that described filler can be selected from one or more in microcrystalline Cellulose, mannitol, low-substituted hydroxypropyl cellulose, polyvinyl alcohol, poly-phthalic acid vinyl acetate, Polyethylene Glycol, sodium alginate, chitosan, sucrose, lactose, starch, dextrin, Icing Sugar, cross linked polyvinyl pyrrolidone, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch, the titanium dioxide, preferred lactose.
Slow releasing tablet of the present invention, it is characterized in that described adhesive can be selected from one or more in water, ethanol, dehydrated alcohol, starch slurry, polyvidone, copolyvidone, crospolyvinylpyrrolidone, hydroxypropyl methylcellulose and/or other cellulose families, preferred polyvidone, copolyvidone.
Slow releasing tablet of the present invention, it is characterized in that described lubricant can select magnesium stearate, micropowder silica gel, Pulvis Talci, hydrogenated vegetable oil, polyethylene glycols for use, month hang in the pure magnesium sulfate one or more, preferred magnesium stearate, micropowder silica gel, Pulvis Talci.
Slow releasing tablet of the present invention is characterized in that described coating material can be selected from ethyl cellulose, starch, methylcellulose, cellulose acetate, cellulose diacetate, Triafol T, acrylic resin, Opadry, Sulisi, preferred Opadry.
Slow releasing tablet of the present invention is characterized in that counting by weight percentage, and it consists of:
Minocycline hydrochloride 5～70%
Slow-release material 0～60%
Filler 0～50%
Adhesive 0～20%
Lubricant 0～6%
The percentage by weight that coating material accounts for slow releasing tablet is:
Coating material 0～40%
The preparation method of described slow releasing tablet of the present invention, it comprises following steps:
(1) plain sheet preparation
(1.1) the preparation of granules minocycline hydrochloride is crossed 80 mesh sieves, and is standby.Take by weighing slow-release material, minocycline hydrochloride, filler and the adhesive of recipe quantity successively; mix homogeneously; add the moderate lubrication agent again; dry granulation behind the mix homogeneously; be circulated to granule between 16 orders～80 orders more than 80%, with 80 now fine powder with moderate lubrication agent mix homogeneously, after mixing with remaining granule again; add the moderate lubrication agent, mix homogeneously.Measure intermediate content.
(1.2) tabletting granule that (1) is made is with shallow circular stamping.Hardness Control is at 7～11KG.
(2) coating adds coating material in the entry under the stirring of propeller blade, is mixed with coating solution, and tablet is put in the coating pan, carries out coating, promptly.
Specific embodiment
Embodiment 1
Prescription
Minocycline hydrochloride 90g
Hydroxypropyl emthylcellulose (K100LV) 80g
Lactose (Flowlac100) 70g
Copolyvidone 20g
Micropowder silica gel 1.3g
Pulvis Talci 3g
Magnesium stearate 3g
Make 1000 altogether
Coating material
Opadry (03B61194) 7.5g
Water 42.5g
Preparation process
(1) plain sheet preparation
(1.1) the preparation of granules minocycline hydrochloride is crossed 80 mesh sieves, and is standby.Take by weighing hydroxypropyl emthylcellulose (K100LV), minocycline hydrochloride, lactose (Flowlac100) and the copolyvidone of recipe quantity successively; mix homogeneously; add an amount of magnesium stearate again; dry granulation behind the mix homogeneously; be circulated to granule between 16 orders～80 orders more than 80%, with 80 now fine powder with recipe quantity micropowder silica gel mix homogeneously, after mixing with remaining granule again; add an amount of magnesium stearate and recipe quantity Pulvis Talci, mix homogeneously.Measure intermediate content.
(1.2) tabletting granule that (1) is made is with the shallow circular stamping of 9mm.Hardness Control is at 7～11KG.
(2) coating adds Opadry (03B61194) in the entry under the stirring of propeller blade, is mixed with coating solution, and tablet is put in the coating pan, carries out coating, promptly.
Embodiment 2
Prescription
Minocycline hydrochloride 45g
Hydroxypropyl emthylcellulose (K100LV) 80g
Lactose (Flowlac100) 70g
Copolyvidone 20g
Micropowder silica gel 1g
Pulvis Talci 2.5g
Magnesium stearate 2.5g
Make 1000 altogether
Coating material
Opadry (03B61194) 7.5g
Water 42.5g
Preparation process
(1) plain sheet preparation
(1.1) the preparation of granules minocycline hydrochloride is crossed 80 mesh sieves, and is standby.Take by weighing hydroxypropyl emthylcellulose (K100LV), minocycline hydrochloride, lactose (Flowlac100) and the copolyvidone of recipe quantity successively; mix homogeneously; add an amount of magnesium stearate again; dry granulation behind the mix homogeneously; be circulated to granule between 16 orders～80 orders more than 80%, with 80 now fine powder with recipe quantity micropowder silica gel mix homogeneously, after mixing with remaining granule again; add an amount of magnesium stearate and recipe quantity Pulvis Talci, mix homogeneously.Measure intermediate content.
(1.2) tabletting granule that (1) is made is with the shallow circular stamping of 8mm.Hardness Control is at 7～11KG.
(2) coating adds Opadry (03B61194) in the entry under the stirring of propeller blade, is mixed with coating solution, and tablet is put in the coating pan, carries out coating, promptly.
Claims (7)
1, a kind of minocycline hydrochloride sustained release tablet is characterized in that being made up of minocycline hydrochloride, slow-release material, filler, adhesive, lubricant, coating material.
2, claim 1 described slow releasing tablet, the minocycline hydrochloride effective dose is 10mg～1000mg, is preferably 100mg～400mg.
3, each described slow releasing tablet among the claim 1-2 is characterized in that:
Described slow-release material can select for use in hydroxypropyl methylcellulose, Sulisi aqueous dispersion, ethyl cellulose, methylcellulose, cellulose acetate-phthalate, hydroxypropyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl-cellulose, cellulose acetate, cellulose diacetate, Triafol T, glyceryl monostearate, the hydroxy methocel one or more to make.Preferred hydroxypropyl methylcellulose.
Described filler can be selected from one or more in microcrystalline Cellulose, mannitol, low-substituted hydroxypropyl cellulose, polyvinyl alcohol, poly-phthalic acid vinyl acetate, Polyethylene Glycol, sodium alginate, chitosan, sucrose, lactose, starch, dextrin, Icing Sugar, cross linked polyvinyl pyrrolidone, cross-linking sodium carboxymethyl cellulose, pregelatinized Starch, the titanium dioxide, preferred lactose.
Described adhesive can be selected from one or more in water, ethanol, dehydrated alcohol, starch slurry, polyvidone, copolyvidone, crospolyvinylpyrrolidone, hydroxypropyl methylcellulose and/or other cellulose families, preferred polyvidone, copolyvidone.
Described lubricant can be selected one or more in magnesium stearate, micropowder silica gel, Pulvis Talci, hydrogenated vegetable oil, polyethylene glycols, month pure magnesium sulfate of extension, preferred magnesium stearate, micropowder silica gel, Pulvis Talci for use.
Described coating material can be selected from ethyl cellulose, starch, methylcellulose, cellulose acetate, cellulose diacetate, Triafol T, acrylic resin, Opadry, Sulisi, preferred Opadry.
4, aforesaid right requires the slow releasing tablet described in the 1-3, it is characterized in that counting by weight percentage, and it consists of:
Minocycline hydrochloride 5～70%
Slow-release material 0～60%
Filler 0～50%
Adhesive 0～20%
Lubricant 0～6%
The percentage by weight that coating material accounts for slow releasing tablet is:
Coating material 0～40%
5, aforesaid right requires the slow releasing tablet described in the 1-4, it is characterized in that calculating by weight, and it consists of:
Minocycline hydrochloride 90g
Hydroxypropyl emthylcellulose (K100LV) 80g
Lactose (Flowlac100) 70g
Copolyvidone 20g
Micropowder silica gel 1.3g
Pulvis Talci 3g
Magnesium stearate 3g
Make 1000 altogether
Coating material
Opadry (03B61194) 7.5g
Water 42.5g
6, aforesaid right requires the slow releasing tablet described in the 1-4, it is characterized in that calculating by weight, and it consists of:
Minocycline hydrochloride 45g
Hydroxypropyl emthylcellulose (K100LV) 80g
Lactose (Flowlac100) 70g
Copolyvidone 20g
Micropowder silica gel 1g
Pulvis Talci 2.5g
Magnesium stearate 2.5g
Make 1000 altogether
Coating material
Opadry (03B61194) 7.5g
Water 42.5g
7, the preparation method of each described slow releasing tablet among the claim 1-6, it comprises following steps:
(1) plain sheet preparation
(1.1) the preparation of granules minocycline hydrochloride is crossed 80 mesh sieves, and is standby.Take by weighing slow-release material, minocycline hydrochloride, filler and the adhesive of recipe quantity successively; mix homogeneously; add the moderate lubrication agent again; mixing all has back dry granulation; be circulated to granule between 16 orders～80 orders more than 80%, with 80 now fine powder with moderate lubrication agent mix homogeneously, after mixing with remaining granule again; add the moderate lubrication agent, mix homogeneously.Measure intermediate content.
(1.2) tabletting granule that (1) is made is with shallow circular stamping.Hardness Control is at 7～11KG.
(2) coating adds coating material in the entry under the stirring of propeller blade, is mixed with coating solution, and tablet is put in the coating pan, carries out coating, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810118869A CN101658501A (en) | 2008-08-26 | 2008-08-26 | Minocycline hydroehloride sustained- release tablets and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810118869A CN101658501A (en) | 2008-08-26 | 2008-08-26 | Minocycline hydroehloride sustained- release tablets and preparation method thereof |
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| Application Number | Title | Priority Date | Filing Date |
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| CN200810118869A Pending CN101658501A (en) | 2008-08-26 | 2008-08-26 | Minocycline hydroehloride sustained- release tablets and preparation method thereof |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101822650A (en) * | 2010-04-28 | 2010-09-08 | 中国科学院上海生命科学研究院湖州营养与健康产业创新中心 | Minocycline hydrochloride sustained release tablet and preparation method thereof |
| CN101940560A (en) * | 2010-09-16 | 2011-01-12 | 孙卫东 | Minocycline hydrochloride sustained-release tablets and method for preparing same with different specifications |
| CN102119931A (en) * | 2011-02-21 | 2011-07-13 | 寿光富康制药有限公司 | Novel metformin hydrochloride slow-releasing tablet and preparation method thereof |
| CN102772384A (en) * | 2012-08-07 | 2012-11-14 | 四川百利药业有限责任公司 | Minocycline hydrochloride sustained release tablet and preparation method thereof |
| US8722650B1 (en) | 2005-06-24 | 2014-05-13 | Medicis Pharmaceutical Corporation | Extended-release minocycline dosage forms |
| CN104606171A (en) * | 2015-02-04 | 2015-05-13 | 上海华源安徽仁济制药有限公司 | Minocycline hydrochloride capsule and preparation method thereof |
| US9192615B2 (en) | 2008-08-06 | 2015-11-24 | Medicis Pharmaceutical Corporation | Method for the treatment of acne and certain dosage forms thereof |
| US9561241B1 (en) | 2011-06-28 | 2017-02-07 | Medicis Pharmaceutical Corporation | Gastroretentive dosage forms for minocycline |
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2008
- 2008-08-26 CN CN200810118869A patent/CN101658501A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8722650B1 (en) | 2005-06-24 | 2014-05-13 | Medicis Pharmaceutical Corporation | Extended-release minocycline dosage forms |
| US9192615B2 (en) | 2008-08-06 | 2015-11-24 | Medicis Pharmaceutical Corporation | Method for the treatment of acne and certain dosage forms thereof |
| CN101822650A (en) * | 2010-04-28 | 2010-09-08 | 中国科学院上海生命科学研究院湖州营养与健康产业创新中心 | Minocycline hydrochloride sustained release tablet and preparation method thereof |
| CN101822650B (en) * | 2010-04-28 | 2012-06-20 | 中国科学院上海生命科学研究院湖州营养与健康产业创新中心 | Minocycline hydrochloride sustained release tablet and preparation method thereof |
| CN101940560A (en) * | 2010-09-16 | 2011-01-12 | 孙卫东 | Minocycline hydrochloride sustained-release tablets and method for preparing same with different specifications |
| CN102119931A (en) * | 2011-02-21 | 2011-07-13 | 寿光富康制药有限公司 | Novel metformin hydrochloride slow-releasing tablet and preparation method thereof |
| CN102119931B (en) * | 2011-02-21 | 2013-02-13 | 寿光富康制药有限公司 | Novel metformin hydrochloride slow-releasing tablet and preparation method thereof |
| US9561241B1 (en) | 2011-06-28 | 2017-02-07 | Medicis Pharmaceutical Corporation | Gastroretentive dosage forms for minocycline |
| CN102772384A (en) * | 2012-08-07 | 2012-11-14 | 四川百利药业有限责任公司 | Minocycline hydrochloride sustained release tablet and preparation method thereof |
| CN104606171A (en) * | 2015-02-04 | 2015-05-13 | 上海华源安徽仁济制药有限公司 | Minocycline hydrochloride capsule and preparation method thereof |
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