CN1732944B - Entecavir dispersible tablet and its preparation process - Google Patents
Entecavir dispersible tablet and its preparation process Download PDFInfo
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- CN1732944B CN1732944B CN 200510097964 CN200510097964A CN1732944B CN 1732944 B CN1732944 B CN 1732944B CN 200510097964 CN200510097964 CN 200510097964 CN 200510097964 A CN200510097964 A CN 200510097964A CN 1732944 B CN1732944 B CN 1732944B
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- 229960000980 entecavir Drugs 0.000 title claims abstract description 46
- YXPVEXCTPGULBZ-WQYNNSOESA-N entecavir hydrate Chemical compound O.C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)C1=C YXPVEXCTPGULBZ-WQYNNSOESA-N 0.000 title claims abstract description 45
- 239000007919 dispersible tablet Substances 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title abstract description 17
- 239000003826 tablet Substances 0.000 abstract description 7
- 239000000463 material Substances 0.000 abstract description 6
- 208000002672 hepatitis B Diseases 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 2
- 238000007796 conventional method Methods 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 13
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 11
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- 239000003795 chemical substances by application Substances 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 229920002472 Starch Polymers 0.000 description 8
- 239000008187 granular material Substances 0.000 description 8
- 239000008107 starch Substances 0.000 description 8
- 235000019698 starch Nutrition 0.000 description 8
- 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 description 7
- 229930195725 Mannitol Natural products 0.000 description 7
- 239000000314 lubricant Substances 0.000 description 7
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- 235000010355 mannitol Nutrition 0.000 description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
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- 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 description 3
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- 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 description 3
- 239000000605 aspartame Substances 0.000 description 3
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- 229960003438 aspartame Drugs 0.000 description 3
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- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
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- 235000019202 steviosides Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000811 xylitol Substances 0.000 description 3
- 235000010447 xylitol Nutrition 0.000 description 3
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 3
- 229960002675 xylitol Drugs 0.000 description 3
- 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 description 2
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- 241000700721 Hepatitis B virus Species 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
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- 239000011230 binding agent Substances 0.000 description 2
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- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229960001855 mannitol Drugs 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 244000099147 Ananas comosus Species 0.000 description 1
- 235000007119 Ananas comosus Nutrition 0.000 description 1
- LBZFKNUMOLETLH-UHFFFAOYSA-N CCCCCCCCCCCCCCCCO[S-](=O)=O.OC(CCC(O)=O)=O.[Na+] Chemical compound CCCCCCCCCCCCCCCCO[S-](=O)=O.OC(CCC(O)=O)=O.[Na+] LBZFKNUMOLETLH-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
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- 102000004190 Enzymes Human genes 0.000 description 1
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- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical class C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- 240000008790 Musa x paradisiaca Species 0.000 description 1
- 235000018290 Musa x paradisiaca Nutrition 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 241000124033 Salix Species 0.000 description 1
- 241000555745 Sciuridae Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- -1 Stepanol MG Chemical compound 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 244000290333 Vanilla fragrans Species 0.000 description 1
- 235000009499 Vanilla fragrans Nutrition 0.000 description 1
- 235000012036 Vanilla tahitensis Nutrition 0.000 description 1
- 241001492404 Woodchuck hepatitis virus Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229940002637 baraclude Drugs 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
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- 238000006243 chemical reaction Methods 0.000 description 1
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- 229940021171 curative drug Drugs 0.000 description 1
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- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- YHAIUSTWZPMYGG-UHFFFAOYSA-L disodium;2,2-dioctyl-3-sulfobutanedioate Chemical compound [Na+].[Na+].CCCCCCCCC(C([O-])=O)(C(C([O-])=O)S(O)(=O)=O)CCCCCCCC YHAIUSTWZPMYGG-UHFFFAOYSA-L 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- QDGZDCVAUDNJFG-FXQIFTODSA-N entecavir (anhydrous) Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)C1=C QDGZDCVAUDNJFG-FXQIFTODSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
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- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
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- 238000009472 formulation Methods 0.000 description 1
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- 238000011031 large-scale manufacturing process Methods 0.000 description 1
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- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
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- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
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- 239000007787 solid Substances 0.000 description 1
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- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
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- 229960005486 vaccine Drugs 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention relates to an Entecavir dispersible tablet for treating hepatitis B and process for its preparation by using Entecavir as raw material, charging auxiliary materials of specific species and proportions, and preparing tablet through the conventional techniques in the pharmaceutical industry.
Description
Technical field
The present invention relates to a kind of new medicinal preparation, particularly relate to entecavir dispersible tablet that is used for the treatment of hepatitis B and preparation method thereof.
Background technology
(M ﹠ M that (HBV) causes in the whole world is the most serious a kind of in liver virus to hepatitis B virus.According to World Health Organization's statistics, global HBV carrier is 3.5 hundred million people approximately, cause dead approximately 100-200 ten thousand people every year.At present, be used for preventative two kinds of sensitized vaccine and the DNA recombiant vaccinies that have; And curative drug commonly used be the a-interferon, it is expensive tolerance and the effective percentage low (only having the patient of 25%-40% to play mitigation) of being difficult to not only.
Entecavir (entecavir) is cyclohexanedione hydroxyphenylpyruvate dioxygenase carbon deoxyguanosine, is a kind of IUDR analog that can effectively suppress hepatitis B virus duplication, has stronger anti-HBV effect.The chemical name of Entecavir is 2-amino-1,9-dihydro-9-[(1S, 3R, 4S)-4-hydroxyl-3-(methylol)-2-methylene cyclopentane]-6H-purine-6-one monohydrate. molecular formula is C12H15N5O3.H2O, and molecular weight 295.3. structural formula is as follows:
Multi-functional varial polymerases is the key enzyme in the liver virus replication, becomes the first-selected target of development viral inhibitors.Copy from the three phases of initial period, reverse transcription phase and DNA dependent DNA synthesis stage the inhibitory action of Entecavir to liver virus.By HBV commonly used being infected the research of marmot animal model, oral Entecavir 0.021-0.5mg/kg can effectively suppress woodchuck hepatitis virus willow HV in 13 months).After drug withdrawal, the viremia of liver can be gone up gradually to the front level for the treatment of.In addition, the result of study of the continued treatment effect of WHV is shown, in case virus replication is effectively suppressed, only can reach with suitable low dosage the purpose of keeping treatment.
Dispersible tablet was a kind of novel pharmaceutical formulation that development in recent years is got up, and British Pharmacopoeia has namely recorded this dosage form as far back as 1993.Chinese Pharmacopoeia is until 2000 just with it as a kind of new dosage form income wherein.Compare ordinary tablet, dispersible tablet requires tablet in the temperature of disintegrate medium during 20 ℃ of left and right, disintegration time is less than 3 minutes, and the granule after disintegrate should be able to whole mistake 710 μ m screen clothes, and said preparation has the advantages such as drug release rate is fast, bioavailability is high, untoward reaction is few.During clinical practice, both can resemble conventional tablet and take, and can put into again water and take after dispersion rapidly, in special case, can also chew or buccal, carry with easy to use, have simultaneously the advantage of solid preparation and liquid preparation concurrently, the patient who is specially adapted to old man, child and dysphagia uses.
On March 30th, 2005, U.S. FDA announces, approval is by tablet and the oral liquid of the medication Entecavir (entecavir, trade name Baraclude) of the treatment adult chronic viral hepatitis B of the research of Bristol-Myers Squibb company, exploitation.Also there is no the dosage form listing of Entecavir on domestic market, but the mechanisms such as a lot of pharmaceutical factory, government department, scientific research institutions are carrying out the research work of this medicine.The entecavir dispersible tablet that the present invention relates to provides a kind of new instructions of taking, facilitates clothes for patients to use.
Adopt the technology of the present invention that Entecavir is prepared into the dispersion sheet, not only expanded the dosage form range of application of Entecavir, particularly through the selection to the present invention's formula, obtained the sense of taste good, disintegrate rapidly, absorb fast, taking convenience, the bioavailability that can improve medicine and blood drug level, improve the novel formulation of antivirus action.
The invention provides a kind of entecavir dispersible tablet, its disintegrate is rapid, and is rapid-action, and bioavailability is high, improves the curative effect for the treatment of hepatitis B, taking convenience, and also preparation method is simple, is fit to large-scale production.
Summary of the invention
The Entecavir poorly water-soluble, the bioavailability of common peroral dosage form is lower, disintegration of tablet is slow, the purpose of this invention is to provide a kind of disintegrate fast, absorb rapidly, can effectively improve bioavailability and the blood drug level of medicine, improve simultaneously Entecavir peroral dosage form-entecavir dispersible tablet of taste, taking convenience, few side effects and preparation method thereof.
Entecavir dispersible tablet provided by the invention contains Entecavir active ingredient and the excipient substance that is fit to make dispersible tablet, and wherein the percentage by weight of Entecavir is 0.001-20%, and the percentage by weight of adjuvant is 80-99.999%.Every of described entecavir dispersible tablet preferably contains Entecavir 0.01-5mg.
The present invention is through selecting, found the excipient substance of suitable entecavir dispersible tablet, described adjuvant comprises disintegrating agent, filler, binding agent, lubricant, wherein the percentage by weight of the amount of filler in dispersible tablet is 20-92%, the percentage by weight of the amount of disintegrating agent in dispersible tablet is 5-30%, the percentage by weight of the amount of correctives in dispersible tablet is 1-30%, and the percentage by weight of the amount of lubricant in dispersible tablet is 0.1-5%.
During its formula forms, if necessary, can also add appropriate correctives, correctives is selected from one or more the mixture in flavoring orange essence, Mint Essence, grape essence, cherry essence, flavoring banana essence, flavoring pineapple essence, vanilla, Fructus Citri Limoniae essence, aspartame, saccharin sodium, steviol glycosides.Consumption is the 0.5-5% of the percentage by weight in dispersible tablet.
The kind of disintegrating agent and the selection of consumption are for can this preparation disintegrate be most important fully at the appointed time.Entecavir dispersible tablet provided by the invention is characterized in that described disintegrating agent is selected from one or more in carboxymethyl starch sodium, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, sodium carboxymethyl cellulose, cross-linking sodium carboxymethyl cellulose, carboxymethylcellulose calcium, carboxymethylcellulose calcium, microcrystalline Cellulose, sodium lauryl sulphate, cetyl sulfo-sodium succinate, sodium dioctyl sulfosuccinate, tween 80.
Filler is selected from one or more of lactose, sucrose, sorbitol, mannitol, xylitol, erythritol, pregelatinized Starch, starch.
Binding agent is selected from a kind of in ethanol, water, ethanol-water solution, syrup, starch slurry, carboxymethylcellulose sodium solution, povidone solution, Magnesiumaluminumsilicate, sodium alginate or several mixture wherein.
Lubricant is selected from one or more the mixture in micropowder silica gel, magnesium stearate, calcium stearate, stearic acid, Pulvis Talci, silicon dioxide, Stepanol MG, PEG4000, PEG6000.
The invention provides the dispersible tablet of Entecavir, it is characterized in that, can adopt the wet granule compression tablet legal system standby.Key step comprises: medicine and various adjuvant pulverized, and after crossing the 80-100 mesh sieve, mix homogeneously.With suitable amount of adhesive soft material processed, granulate with the 12-24 mesh sieve, 40-80 ℃ dry 4-5 hour, 18-24 mesh sieve granulate, add other adjuvant mix homogeneously after tabletting get final product.Wherein disintegrating agent can adopt add, method that Nei Jia or inside and outside mixing add.Above various operation is that those skilled in the art are in common knowledge and familiar.
The invention provides the dispersible tablet of Entecavir, it is characterized in that, can also adopt the direct powder compression preparation.Key step comprises: medicine and various adjuvant pulverized, and after crossing the 80-100 mesh sieve, mix homogeneously, tab weighs and pressure, direct compression.
The most preferred formula composition of the present invention is listed in embodiment.
The specific embodiment
By following instance, entecavir dispersible tablet of the present invention is done further illustrating, but be not limited in following instance.
Embodiment 1:
Prescription:
Entecavir 0.5g
Mannitol 25g
Microcrystalline Cellulose 137.5g
Crosslinked carboxymethyl fecula sodium 19g
Crospolyvinylpyrrolidone 8g
Starch slurry 7g (with amylometer)
Magnesium stearate 3g
Make altogether 1000
Preparation method:
First above-mentioned each material was pulverized respectively 100 mesh sieves, after Entecavir, mannitol, microcrystalline Cellulose, abundant mix homogeneously, add appropriate starch slurry to make soft material, 16 mesh sieves are granulated, 60 ℃ after dry 3-4 hour, 16 mesh sieve granulate add disintegrating agent crosslinked carboxymethyl fecula sodium, crospolyvinylpyrrolidone and magnesium stearate lubricant outward, after mixing, be pressed into entecavir dispersible tablet.
Embodiment 2:
Prescription:
Entecavir 0.25g
Mannitol 36g
Microcrystalline Cellulose 45g
Crosslinked carboxymethyl fecula sodium 6g
Aspartame 3.6g
Fructus Citri Limoniae essence 1.2g
Pulvis Talci 1.8g
Starch slurry 6g (with amylometer)
Make altogether 1000
Preparation method:
First above-mentioned each material was pulverized respectively 100 mesh sieves, after Entecavir, mannitol, microcrystalline Cellulose, abundant mix homogeneously, add appropriate starch slurry to make soft material, 16 mesh sieves are granulated, and 80 ℃ of dryings are after 3 hours, 16 mesh sieve granulate, add disintegrating agent crosslinked carboxymethyl fecula sodium outward, correctives aspartame, Fructus Citri Limoniae essence, lubricant Pulvis Talci, after mixing, be pressed into entecavir dispersible tablet.
Embodiment 3:
Prescription:
Entecavir 2g
Xylitol 40g
Microcrystalline Cellulose 42g
Crospolyvinylpyrrolidone 12g
L-HPC 6g
Polyvinylpyrrolidone 50% alcoholic solution 1.8g (in polyvinylpyrrolidone)
Steviol glycosides 2.5g
Cherry essence 2.5g
PEG6000 1.5g
Make altogether 1000
Preparation method:
First above-mentioned each material was pulverized respectively 100 mesh sieves, after Entecavir, xylitol, the abundant mix homogeneously of microcrystalline Cellulose, add appropriate polyvinylpyrrolidone 50% alcoholic solution to make soft material, 24 mesh sieves are granulated, and 60 ℃ after dry 2-3 hour, 20 mesh sieve granulate, add disintegrating agent crospolyvinylpyrrolidone, L-HPC outward, correctives steviol glycosides, cherry essence, lubricant PEG6000, after mixing, be pressed into entecavir dispersible tablet.
Embodiment 4:
Prescription:
Entecavir 2g
Microcrystalline Cellulose 100g
Crospolyvinylpyrrolidone 18g
Sucrose 32g
Mannitol 28g
70% alcoholic solution is appropriate
Grape essence 2.5g
Cherry essence 2.5g
Pulvis Talci 1.5g
Make altogether 1000
Preparation method:
First above-mentioned each material was pulverized respectively 100 mesh sieves, after Entecavir, mannitol, sucrose, the abundant mix homogeneously of microcrystalline Cellulose, add appropriate 70%7 alcoholic solutions to make soft material, 24 mesh sieves are granulated, and 60 ℃ after dry 1-2 hour, 20 mesh sieve granulate, add disintegrating agent crospolyvinylpyrrolidone, correctives grape essence, cherry essence outward, the lubricant Pulvis Talci after mixing, is pressed into entecavir dispersible tablet.
Embodiment 5
Prescription:
Entecavir 1g
Lactose 10.5g
Pregelatinized Starch 42g
Microcrystalline Cellulose 48g
Low-substituted hydroxypropyl cellulose 18g
Micropowder silica gel 1.5g
Make altogether 1000
Preparation method:
First above-mentioned each material is pulverized respectively 100 mesh sieves, after Entecavir, lactose, pregelatinized Starch, microcrystalline Cellulose, the abundant mix homogeneously of low-substituted hydroxypropyl cellulose, regulated pressure, be pressed into entecavir dispersible tablet.
Claims (1)
1. an entecavir dispersible tablet, is characterized in that, fills a prescription composed as follows:
Priority Applications (1)
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| CN 200510097964 CN1732944B (en) | 2005-09-02 | 2005-09-02 | Entecavir dispersible tablet and its preparation process |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200510097964 CN1732944B (en) | 2005-09-02 | 2005-09-02 | Entecavir dispersible tablet and its preparation process |
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| CN1732944A CN1732944A (en) | 2006-02-15 |
| CN1732944B true CN1732944B (en) | 2013-05-08 |
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Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101244044B (en) * | 2008-03-24 | 2013-01-23 | 上海国创医药有限公司 | Entecavir dispersible tablet and preparation thereof |
| CN101703489B (en) * | 2009-11-10 | 2011-05-11 | 金三九 | Entecavir soft capsule |
| CN102144983B (en) * | 2011-04-06 | 2012-11-14 | 福建广生堂药业股份有限公司 | Entecavir dispersible tablets and preparation method thereof |
| CN102552920B (en) * | 2012-02-20 | 2014-01-29 | 北京协和药厂 | Entecavir-containing medicinal composition and preparation method thereof |
| CN105287419A (en) * | 2015-12-01 | 2016-02-03 | 李正梅 | Anti-hepatitis B entecavir dispersible tablet |
| CN110420188A (en) * | 2019-08-06 | 2019-11-08 | 浙江爱诺生物药业股份有限公司 | A method of improving Entecavir tablet uniformity of dosage units |
| CN110354129A (en) * | 2019-08-19 | 2019-10-22 | 苏州扬厉医药科技有限公司 | A kind of new drug pharmaceutical composition that treating hepatitis B and preparation method |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1310999A (en) * | 2000-02-29 | 2001-09-05 | 布里斯托尔-迈尔斯斯奎布公司 | Low dose Etikavi Prepn. and the use thereof |
| CN1658844A (en) * | 2002-04-08 | 2005-08-24 | 布里斯托尔-迈尔斯斯奎布公司 | Low dose liquid entecavir formulations and use |
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2005
- 2005-09-02 CN CN 200510097964 patent/CN1732944B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1310999A (en) * | 2000-02-29 | 2001-09-05 | 布里斯托尔-迈尔斯斯奎布公司 | Low dose Etikavi Prepn. and the use thereof |
| CN1658844A (en) * | 2002-04-08 | 2005-08-24 | 布里斯托尔-迈尔斯斯奎布公司 | Low dose liquid entecavir formulations and use |
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| 毕殿洲.药剂学（国家执业药师资格考试应试指南.中国医药科技出版社,2000,139，141-145. * |
| 沈岚等.分散片的研究进展.中成药26 2.2004,26(2),145-148. |
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