CN102198110A - Tenofovir disoproxil fumarate dispersible tablets and preparation method thereof - Google Patents
Tenofovir disoproxil fumarate dispersible tablets and preparation method thereof Download PDFInfo
- Publication number
- CN102198110A CN102198110A CN 201110141124 CN201110141124A CN102198110A CN 102198110 A CN102198110 A CN 102198110A CN 201110141124 CN201110141124 CN 201110141124 CN 201110141124 A CN201110141124 A CN 201110141124A CN 102198110 A CN102198110 A CN 102198110A
- Authority
- CN
- China
- Prior art keywords
- fumaric acid
- pyrrole furan
- acid tenofovir
- filler
- surfactant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 title claims abstract description 74
- 239000007919 dispersible tablet Substances 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- 229960004693 tenofovir disoproxil fumarate Drugs 0.000 title abstract description 7
- 239000000945 filler Substances 0.000 claims abstract description 35
- 239000000314 lubricant Substances 0.000 claims abstract description 33
- 239000004094 surface-active agent Substances 0.000 claims abstract description 33
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 126
- 229960004556 tenofovir Drugs 0.000 claims description 67
- 239000001530 fumaric acid Substances 0.000 claims description 63
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 63
- 239000003795 chemical substances by application Substances 0.000 claims description 40
- LTVDTKRMOQDRCH-UHFFFAOYSA-N furan;1h-pyrrole Chemical class C=1C=CNC=1.C=1C=COC=1 LTVDTKRMOQDRCH-UHFFFAOYSA-N 0.000 claims description 40
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 40
- -1 pyrrole furan ester Chemical class 0.000 claims description 38
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 28
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 28
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 28
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 24
- 108010011485 Aspartame Proteins 0.000 claims description 20
- 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 20
- 229930195725 Mannitol Natural products 0.000 claims description 20
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 20
- 239000000605 aspartame Substances 0.000 claims description 20
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 20
- 235000010357 aspartame Nutrition 0.000 claims description 20
- 229960003438 aspartame Drugs 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 20
- 235000019359 magnesium stearate Nutrition 0.000 claims description 20
- 239000000594 mannitol Substances 0.000 claims description 20
- 235000010355 mannitol Nutrition 0.000 claims description 20
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 20
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 19
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 18
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 18
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims description 18
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 18
- 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 17
- 239000007864 aqueous solution Substances 0.000 claims description 17
- 239000011230 binding agent Substances 0.000 claims description 17
- 239000008101 lactose Substances 0.000 claims description 17
- 239000008187 granular material Substances 0.000 claims description 16
- 238000002156 mixing Methods 0.000 claims description 14
- 229920000881 Modified starch Polymers 0.000 claims description 13
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 13
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 13
- 206010013786 Dry skin Diseases 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 11
- 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 10
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 10
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 10
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- 230000001476 alcoholic effect Effects 0.000 claims description 8
- 239000000741 silica gel Substances 0.000 claims description 8
- 229910002027 silica gel Inorganic materials 0.000 claims description 8
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 6
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 6
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- 239000002994 raw material Substances 0.000 claims description 3
- 238000005550 wet granulation Methods 0.000 claims description 3
- 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 claims description 2
- 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 2
- 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 claims description 2
- 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 claims description 2
- 239000004378 Glycyrrhizin Substances 0.000 claims description 2
- 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 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 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
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 claims description 2
- 238000004132 cross linking Methods 0.000 claims description 2
- 229940109275 cyclamate Drugs 0.000 claims description 2
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 claims description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 claims description 2
- 229960004949 glycyrrhizic acid Drugs 0.000 claims description 2
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 claims description 2
- 235000019410 glycyrrhizin Nutrition 0.000 claims description 2
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 229920000053 polysorbate 80 Polymers 0.000 claims description 2
- 229940085605 saccharin sodium Drugs 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 235000015424 sodium Nutrition 0.000 claims description 2
- KBZCQLGWSYSOHN-UHFFFAOYSA-N sodium butanedioic acid 1-sulfinatooxydodecane Chemical compound CCCCCCCCCCCCO[S-](=O)=O.OC(CCC(O)=O)=O.[Na+] KBZCQLGWSYSOHN-UHFFFAOYSA-N 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 235000010356 sorbitol Nutrition 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 229940013618 stevioside Drugs 0.000 claims description 2
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 claims description 2
- 235000019202 steviosides Nutrition 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- 239000003826 tablet Substances 0.000 abstract description 9
- 238000004090 dissolution Methods 0.000 abstract description 5
- 239000004615 ingredient Substances 0.000 abstract 3
- 239000007884 disintegrant Substances 0.000 abstract 1
- 239000006185 dispersion Substances 0.000 abstract 1
- 239000000796 flavoring agent Substances 0.000 abstract 1
- 235000013355 food flavoring agent Nutrition 0.000 abstract 1
- 238000000034 method Methods 0.000 description 7
- 229960001375 lactose Drugs 0.000 description 5
- 241000700721 Hepatitis B virus Species 0.000 description 4
- 241000725303 Human immunodeficiency virus Species 0.000 description 4
- 229960001855 mannitol Drugs 0.000 description 4
- 239000003651 drinking water Substances 0.000 description 3
- 235000020188 drinking water Nutrition 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 208000019505 Deglutition disease Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 108020005202 Viral DNA Proteins 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 238000009702 powder compression Methods 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- SOPCSZVJRDRWIT-MCDZGGTQSA-N OP(O)(=O)OP(O)(=O)OP(O)(O)=O.O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O.O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 SOPCSZVJRDRWIT-MCDZGGTQSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- XQRLCLUYWUNEEH-UHFFFAOYSA-N diphosphonic acid Chemical compound OP(=O)OP(O)=O XQRLCLUYWUNEEH-UHFFFAOYSA-N 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses tenofovir disoproxil fumarate dispersible tablets and a preparation method thereof. The tenofovir disoproxil fumarate dispersible tablets are prepared from tenofovir disoproxil fumarate as an effective pharmaceutical ingredient and pharmaceutically acceptable auxiliary ingredients, wherein the pharmaceutically acceptable auxiliary ingredients comprise a filler, a disintegrant, a lubricant, a surfactant and a flavoring agent. The tenofovir disoproxil fumarate dispersible tablets prepared by the invention have appropriate hardness, small weight difference, bright and clean tablet surfaces and good taste, fully meet the requirements on the disintegration time and dispersion uniformity of dispersible tablets, and notably improve the pharmaceutical bioavailability, and in addition, the tenofovir disoproxil fumarate dispersible tablets have quick dissolution rate, the dissolution percentage of the product is about 80-90% in 2 minutes, and the product is almost completely dissolved in 5 minutes.
Description
(1) technical field
The present invention relates to the dispersible tablet formulation and preparation method thereof of the medicine fumaric acid tenofovir two pyrrole furan esters of a kind of anti AIDS virus (HIV), hepatitis B virus (HBV).
(2) background technology
Fumaric acid tenofovir two pyrrole furan esters (English name: be the esters prodrug of tenofovir Tenofovir disoproxil fumarate), belong to novel nucleoside acids reverse transcriptase inhibitors, can suppress duplicating of HIV, HBV virus.Its main mechanism is that oral posthydrolysis is a tenofovir, tenofovir is by the cell kinase phosphorylation, generation has the metabolite tenofovir diphosphonic acid of pharmacologically active, the latter and 5 '-deoxyadenosine triphosphate acid competition, participate in the synthetic of viral DNA, enter viral DNA after owing to lack 3 '-the 0H group, thereby cause DNA to prolong being obstructed, and then the duplicating of blocking virus.Show that from present clinical practice it has significant anti-HIV, HBV virus curative effect, and its toxicity to human body is very little, is expected to become a line medication.
Fumaric acid tenofovir two pyrrole furan ester conventional tablets in the U.S., European Union, Turkey, Australia, New Zealand, add take, listing such as China, be used for the treatment of HIV or HBV.This medicine is at existing report with in using, what really only relate to is the medicine of its conventional tablet dosage form, one all need help swallow or directly swallow the conventional tablet medicine by drinking-water when taking, this just to some as old people, child with there is patient's compliance of dysphagia poor, also have in the use of going out or lack under the specific condition such as drinking water also can be subjected to very big restriction.In addition, conventional tablet one onset is slow comparatively speaking, to reach the peak slow, and dispersible tablet disintegrate result of extraction is good, can significantly improve bioavailability.
(3) summary of the invention
The technical problem to be solved in the present invention provides a kind of fumaric acid tenofovir two pyrrole furan ester dispersible tablet drug preparations, and this dispersible tablet is than existing conventional tablet, and disintegration time is short, the medicine stripping is rapid, rapid-action, bioavailability is high, and taking convenience.
For solving the problems of the technologies described above, the present invention adopts following technical scheme:
A kind of fumaric acid tenofovir two pyrrole furan ester dispersible tablets, be to be the active drug composition with fumaric acid tenofovir two pyrrole furan esters, make jointly with the acceptable auxiliary element of pharmacy, the acceptable auxiliary element of described pharmacy comprises filler, disintegrating agent, lubricant, surfactant and correctives; With 100%, the percentage by weight of each raw material components is expressed as follows in the gross weight of fumaric acid tenofovir two pyrrole furan esters, filler, disintegrating agent, lubricant, surfactant and correctives:
Described filler is selected from following a kind of or several combination arbitrarily: microcrystalline Cellulose, lactose, sucrose, pregelatinized Starch, starch, sorbitol, mannitol, xylitol;
Described disintegrating agent is selected from following a kind of or several combination arbitrarily: low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, sodium carboxymethyl cellulose, carboxymethylcellulose calcium;
Described lubricant is selected from following a kind of or several combination arbitrarily: magnesium stearate, calcium stearate, stearic acid, Pulvis Talci, micropowder silica gel, Polyethylene Glycol;
Surfactant is selected from following a kind of or several combination arbitrarily: sodium lauryl sulphate, Stepanol MG, dodecyl sulfo-sodium succinate, Tween 80;
Described correctives is selected from following a kind of or several combination arbitrarily: aspartame, cyclamate, glycyrrhizin, stevioside, saccharin sodium.
Further, the percentage by weight of the preferred described fumaric acid tenofovir two pyrrole furan esters of the present invention, filler, disintegrating agent, lubricant, surfactant and correctives is expressed as follows:
Further, the percentage by weight of the preferred described fumaric acid tenofovir two pyrrole furan esters of the present invention, filler, disintegrating agent, lubricant, surfactant and correctives is expressed as follows:
Further, described filler is preferred one of following: the combination of microcrystalline Cellulose 10～35%, lactose 10～40% and mannitol 0～30%, the combination of microcrystalline Cellulose 10～35%, pregelatinized Starch 10～40% and mannitol 0～30%.Above-mentioned percentage ratio also is that gross weight in fumaric acid tenofovir two pyrrole furan esters, filler, disintegrating agent, lubricant, surfactant and correctives is with 100%.
Further, described filler is preferred one of following: the combination of microcrystalline Cellulose 10～25%, lactose 10～25% and mannitol 0～20%, the combination of microcrystalline Cellulose 10～25%, pregelatinized Starch 15～25% and mannitol 0～20%.
Further, preferred following one or both the combination of described disintegrating agent: low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone.
Further, preferred following one or both the combination of described lubricant: magnesium stearate, micropowder silica gel.
Further, described surfactant preferably sodium dodecyl sulfate.
Further, the preferred aspartame of described correctives.
Fumaric acid tenofovir two pyrrole furan ester dispersible tablets of the present invention, with fumaric acid tenofovir two pyrrole furan esters is the active drug composition, make jointly with the acceptable auxiliary element of pharmacy, the acceptable auxiliary element of described pharmacy can also comprise binding agent, described binding agent can be selected from following a kind of: water, ethanol, ethanol water, amidin, the polyvidone aqueous solution, the polyvidone alcoholic solution, polyvidone ethanol water, hydroxypropyl emthylcellulose aqueous solution, the hydroxypropyl emthylcellulose alcoholic solution, the hydroxypropyl emthylcellulose ethanol water, sodium carboxymethyl cellulose solution, sodium carboxymethyl cellulose alcoholic solution, the sodium carboxymethyl cellulose ethanol water, hydroxypropyl cellulose aqueous solution, hydroxypropyl cellulose alcoholic solution, hydroxypropyl cellulose ethanol water.
Further, described binding agent is preferred one of following: mass fraction is that 2～10% amidin, mass fraction are that 2～10% polyvidone aqueous solution, mass fraction are 2～10% hydroxypropyl emthylcellulose aqueous solution.
Among the present invention, the addition of described binding agent is recommended as 0.1～0.9ml/g in the gross weight of fumaric acid tenofovir two pyrrole furan esters, filler, disintegrating agent, lubricant, surfactant and correctives, is preferably 0.25～0.8ml/g.
Preferred version of the present invention is:
A kind of fumaric acid tenofovir two pyrrole furan ester dispersible tablets, be to be the active drug composition with fumaric acid tenofovir two pyrrole furan esters, make jointly with the acceptable auxiliary element of pharmacy, the acceptable auxiliary element of described pharmacy is made up of filler, disintegrating agent, lubricant, surfactant and correctives; With 100%, the percentage by weight of each raw material components is expressed as follows in the gross weight of fumaric acid tenofovir two pyrrole furan esters, filler, disintegrating agent, lubricant, surfactant and correctives:
It is one of following that described filler is selected from: the combination of microcrystalline Cellulose 10～25%, lactose 10～25% and mannitol 0～20%, the combination of microcrystalline Cellulose 10～25%, pregelatinized Starch 15～25% and mannitol 0～20%;
Described disintegrating agent is selected from following one or both combination: low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone;
Described lubricant is selected from following one or both combination: magnesium stearate, micropowder silica gel;
Described surfactant is selected from sodium lauryl sulphate;
Described correctives is selected from aspartame.
Another preferred version of the present invention is:
A kind of fumaric acid tenofovir two pyrrole furan ester dispersible tablets, be to be the active drug composition with fumaric acid tenofovir two pyrrole furan esters, make jointly with the acceptable auxiliary element of pharmacy, the acceptable auxiliary element of described pharmacy is made up of filler, disintegrating agent, lubricant, surfactant, correctives and binding agent; The addition of described binding agent is counted 0.25～0.8ml/g with the gross weight of fumaric acid tenofovir two pyrrole furan esters, filler, disintegrating agent, lubricant, surfactant and correctives; With 100%, shared separately percentage by weight is expressed as follows the addition of described filler, disintegrating agent, lubricant, surfactant, correctives in the gross weight of fumaric acid tenofovir two pyrrole furan esters, filler, disintegrating agent, lubricant, surfactant and correctives:
It is one of following that described filler is selected from: the combination of microcrystalline Cellulose 10～25%, lactose 10～25% and mannitol 0～20%, the combination of microcrystalline Cellulose 10～25%, pregelatinized Starch 15～25% and mannitol 0～20%;
Described disintegrating agent is selected from following one or both combination: low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone;
Described lubricant is selected from following one or both combination: magnesium stearate, micropowder silica gel;
Described surfactant is selected from sodium lauryl sulphate;
Described correctives is selected from aspartame;
It is one of following that described binding agent is selected from: mass fraction is that 2～10% amidin, mass fraction are that 2～10% polyvidone aqueous solution, mass fraction are 2～10% hydroxypropyl emthylcellulose aqueous solution.
The above-mentioned fumaric acid tenofovir two pyrrole furan ester dispersible tablet drug preparations of the present invention can obtain by wet granulation or dry granulation or fluidized bed granulation or spray granulation or direct powder compression preparation.
Wherein the process of direct powder compression is:
A kind of preparation method of fumaric acid tenofovir two pyrrole furan ester dispersible tablets comprises the following steps:
1) with fumaric acid tenofovir two pyrrole furan esters, filler, disintegrating agent, correctives, lubricant, surfactant abundant mix homogeneously and pulverized 100 mesh sieves in proportion;
2) behind the mixing, measure content, tab weight is made sheet.
Wherein, the process of wet granule compression tablet method is:
A kind of preparation method of fumaric acid tenofovir two pyrrole furan ester dispersible tablets, the acceptable auxiliary element of described pharmacy also comprises binding agent, described preparation method comprises the following steps:
A) with fumaric acid tenofovir two pyrrole furan esters, filler and correctives or fumaric acid tenofovir two pyrrole furan esters, filler, correctives and the abundant mix homogeneously of disintegrating agent and pulverized 100 mesh sieves;
B) add binding agent, 20 mesh sieve wet granulations;
C) 50～60 ℃ of dryings are after 2～4 hours, 18 mesh sieve granulate;
D) add lubricant and surfactant or lubricant, surfactant and disintegrating agent again, behind the mixing, measure content, tab weight is made sheet;
In above-mentioned steps (a) and the step (d), one of them step need add disintegrating agent.
In the above-mentioned wet granule compression tablet procedure, disintegrating agent is made granule with the prescription powder, is referred to as addition in the disintegrating agent; Disintegrating agent mixes the back tabletting and is referred to as the outer addition of disintegrating agent with dried granules; Add in the disintegrating agent and add the disintegration rate that all can influence dispersible tablet, can adopt interior addition, also can adopt outer addition, can also in add, add common use; interiorly add, when adding common use, disintegrating agent can be identical, also can be different; These preparations and processing method all are as well known to those skilled in the art and familiar.
Compared with prior art, beneficial effect of the present invention is:
1, the fumaric acid tenofovir two pyrrole furan ester dispersible tablets that make of the present invention have suitable hardness, weight differential little, unilateral bright and clean, mouthfeel good; Meet the requirement of dispersible tablet disintegration and dispersing uniformity fully; Dissolution rate is fast, in 2min the stripping percentage rate of this product about 80-90%, substantially all strippings of this product in 5min.
Therefore as the said medicine of the present invention of intestines and stomach route of administration, its dispersing uniformity and dissolution and all very desirable to sheltering of adverse drug taste, can solve some old peoples, child satisfactorily and the patient of dysphagia is arranged and go out or lack the problem of taking under the specific condition such as drinking water, when taking medicine is contained in and suck clothes in the mouth or medicine is put into warm water disperse to swallow; Suck clothes, be dispersed in and swallow in the water or directly swallow for optional the selecting of usual crowd; Foregoing invention solved well usual crowd and very the crowd can satisfy different patients' medication demand to the compliance of this medicine; Above-mentioned in vitro tests shows that this pharmaceutical preparation can significantly improve bioavailability.
2, said medicine preparation of the present invention can directly use conventional tablet pharmaceutical equipment to produce and use the pressing process preparation, need not overlapping investment, and preparation technology is simple and convenient, has good market prospect.
(4) specific embodiment
Below again foregoing of the present invention is described in further detail by specific embodiment.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only is confined to following example.Under the situation that does not break away from the above-mentioned technological thought of the present invention, various replacements or change according to ordinary skill knowledge and customary means are made all should comprise within the scope of the invention.
Embodiment 1:
Prescription:
Preparation method: with fumaric acid tenofovir two pyrrole furan esters, mannitol, microcrystalline Cellulose, lactose, low-substituted hydroxypropyl cellulose, the abundant mix homogeneously of aspartame and pulverized 100 mesh sieves, make 20 order wet granulars with an amount of 5% amidin, in 55 ℃ of dryings after 3 hours, 18 mesh sieve granulate, after adding polyvinylpolypyrrolidone, sodium lauryl sulphate, the abundant mixing of magnesium stearate, measure content, tab weight is made sheet.
Embodiment 2:
Prescription:
Preparation method: with fumaric acid tenofovir two pyrrole furan esters, mannitol, microcrystalline Cellulose, lactose, low-substituted hydroxypropyl cellulose, the abundant mix homogeneously of aspartame and pulverized 100 mesh sieves, make 20 order wet granulars with an amount of 3% polyvidone aqueous solution, in 55 ℃ of dryings after 3.5 hours, 18 mesh sieve granulate, after adding polyvinylpolypyrrolidone, sodium lauryl sulphate, micropowder silica gel, the abundant mixing of magnesium stearate, measure content, tab weight is made sheet.
Embodiment 3:
Prescription:
Preparation method: with fumaric acid tenofovir two pyrrole furan esters, microcrystalline Cellulose, lactose, low-substituted hydroxypropyl cellulose, the abundant mix homogeneously of aspartame and pulverized 100 mesh sieves, make 20 order wet granulars with an amount of 5% amidin, in 50 ℃ of dryings after 3 hours, 18 mesh sieve granulate, after adding polyvinylpolypyrrolidone, sodium lauryl sulphate, the abundant mixing of magnesium stearate, measure content, tab weight is made sheet.
Embodiment 4:
Prescription:
Preparation method: with fumaric acid tenofovir two pyrrole furan esters, mannitol, microcrystalline Cellulose, pregelatinized Starch, low-substituted hydroxypropyl cellulose, the abundant mix homogeneously of aspartame and pulverized 100 mesh sieves, make 20 order wet granulars with an amount of 5% polyvidone aqueous solution, in 55 ℃ of dryings after 3 hours, 18 mesh sieve granulate, after adding polyvinylpolypyrrolidone, sodium lauryl sulphate, the abundant mixing of magnesium stearate, measure content, tab weight is made sheet.
Embodiment 5:
Prescription:
Preparation method: with fumaric acid tenofovir two pyrrole furan esters, mannitol, microcrystalline Cellulose, pregelatinized Starch, low-substituted hydroxypropyl cellulose, the abundant mix homogeneously of aspartame and pulverized 100 mesh sieves, make 20 order wet granulars with an amount of 4% hydroxypropyl emthylcellulose aqueous solution, in 55 ℃ of dryings after 3.5 hours, 18 mesh sieve granulate, after adding polyvinylpolypyrrolidone, sodium lauryl sulphate, micropowder silica gel, the abundant mixing of magnesium stearate, measure content, tab weight is made sheet.
Embodiment 6:
Prescription:
Preparation method: with fumaric acid tenofovir two pyrrole furan esters, microcrystalline Cellulose, pregelatinized Starch, low-substituted hydroxypropyl cellulose, the abundant mix homogeneously of aspartame and pulverized 100 mesh sieves, make 20 order wet granulars with an amount of 8% amidin, in 50 ℃ of dryings after 3 hours, 18 mesh sieve granulate, after adding polyvinylpolypyrrolidone, sodium lauryl sulphate, the abundant mixing of magnesium stearate, measure content, tab weight is made sheet.
Embodiment 7:
Prescription:
Preparation method: with fumaric acid tenofovir two pyrrole furan esters, microcrystalline Cellulose, lactose, 51.2g polyvinylpolypyrrolidone, the abundant mix homogeneously of aspartame and pulverized 100 mesh sieves, make 20 order wet granulars with an amount of 5% polyvidone aqueous solution, in 55 ℃ of dryings after 3 hours, 18 mesh sieve granulate, after adding 44g polyvinylpolypyrrolidone, sodium lauryl sulphate, the abundant mixing of magnesium stearate, measure content, tab weight is made sheet.
Embodiment 8:
Prescription:
Preparation method: with fumaric acid tenofovir two pyrrole furan esters, microcrystalline Cellulose, lactose, 50g low-substituted hydroxypropyl cellulose, the abundant mix homogeneously of aspartame and pulverized 100 mesh sieves, make 20 order wet granulars with an amount of 5% amidin, in 55 ℃ of dryings after 3 hours, 18 mesh sieve granulate, after adding 52.5g low-substituted hydroxypropyl cellulose, sodium lauryl sulphate, the abundant mixing of magnesium stearate, measure content, tab weight is made sheet.
Embodiment 9:
Prescription:
Preparation method: with fumaric acid tenofovir two pyrrole furan esters, mannitol, microcrystalline Cellulose, lactose, low-substituted hydroxypropyl cellulose, the abundant mix homogeneously of aspartame and pulverized 100 mesh sieves, make 20 order wet granulars with an amount of 5% polyvidone aqueous solution, in 55 ℃ of dryings after 2.5 hours, 18 mesh sieve granulate, after adding polyvinylpolypyrrolidone, sodium lauryl sulphate, the abundant mixing of magnesium stearate, measure content, tab weight is made sheet.
Embodiment 10:
Prescription:
Preparation method: with fumaric acid tenofovir two pyrrole furan esters, mannitol, microcrystalline Cellulose, lactose, low-substituted hydroxypropyl cellulose, the abundant mix homogeneously of aspartame and pulverized 100 mesh sieves, make 20 order wet granulars with an amount of 5% amidin, in 55 ℃ of dryings after 3 hours, 18 mesh sieve granulate, after adding polyvinylpolypyrrolidone, sodium lauryl sulphate, the abundant mixing of magnesium stearate, measure content, tab weight is made sheet.
Embodiment 11:
Prescription:
Preparation method: with fumaric acid tenofovir two pyrrole furan esters, microcrystalline Cellulose, lactose, polyvinylpolypyrrolidone, aspartame, sodium lauryl sulphate, the abundant mix homogeneously of magnesium stearate and pulverized 100 mesh sieves, measure content, the heavy directly compacting of tab is in blocks.
Embodiment 12:
Prescription:
Preparation method: with fumaric acid tenofovir two pyrrole furan esters, microcrystalline Cellulose, pregelatinized Starch, low-substituted hydroxypropyl cellulose, aspartame, sodium lauryl sulphate, the abundant mix homogeneously of magnesium stearate and pulverized 100 mesh sieves, measure content, the heavy directly compacting of tab in flakes.
Embodiment 13:
Prescription:
Preparation method: with fumaric acid tenofovir two pyrrole furan esters, microcrystalline Cellulose, lactose, polyvinylpolypyrrolidone, aspartame, sodium lauryl sulphate, the abundant mix homogeneously of magnesium stearate and pulverized 100 mesh sieves, measure content, the heavy directly compacting of tab is in blocks.
Embodiment 14:
Prescription:
Preparation method: with fumaric acid tenofovir two pyrrole furan esters, microcrystalline Cellulose, pregelatinized Starch, low-substituted hydroxypropyl cellulose, aspartame, sodium lauryl sulphate, the abundant mix homogeneously of magnesium stearate and pulverized 100 mesh sieves, measure content, the heavy directly compacting of tab in flakes.
The analytical test result of the fumaric acid tenofovir two pyrrole furan ester dispersible tablets that the above embodiment of the present invention is prepared:
(1) weight differential of the prepared fumaric acid tenofovir two pyrrole furan ester dispersible tablets of above embodiment little, unilateral bright and clean, hardness is moderate, mouthfeel good.
(2) the dispersing uniformity result of the test shows: according to the method for two regulations of 2010 editions Chinese Pharmacopoeias, get 6 of this product, put in the 250ml beaker, add about 20 ℃ water 100ml, and jolting 3 minutes, the whole disintegrates of above embodiment dispersible tablet are also passed through sieve No. two.
(3) the dissolution result of the test shows: according to dissolution method (2010 editions two appendix XC second methods of Chinese Pharmacopoeia), with 0.01mol/L hydrochloric acid solution 900ml is dissolution medium, rotating speed is that per minute 50 changes, operation in accordance with the law, measure every stripping quantity according to ultraviolet visible spectrophotometry, the result be the stripping percentage rate of this product in 2min about 80-90%, substantially all strippings of this product in 5min.The results are shown in following table 1.
The accumulation stripping percentage rate of each each time point of embodiment of table 1.
Claims (10)
1. fumaric acid tenofovir two pyrrole furan ester dispersible tablets, be to be the active drug composition with fumaric acid tenofovir two pyrrole furan esters, make jointly with the acceptable auxiliary element of pharmacy, the acceptable auxiliary element of described pharmacy comprises filler, disintegrating agent, lubricant, surfactant and correctives; With 100%, the percentage by weight of each raw material components is expressed as follows in the gross weight of fumaric acid tenofovir two pyrrole furan esters, filler, disintegrating agent, lubricant, surfactant and correctives:
Described filler is selected from following a kind of or several combination arbitrarily: microcrystalline Cellulose, lactose, sucrose, pregelatinized Starch, starch, sorbitol, mannitol, xylitol;
Described disintegrating agent is selected from following a kind of or several combination arbitrarily: low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, sodium carboxymethyl cellulose, carboxymethylcellulose calcium;
Described lubricant is selected from following a kind of or several combination arbitrarily: magnesium stearate, calcium stearate, stearic acid, Pulvis Talci, micropowder silica gel, Polyethylene Glycol;
Surfactant is selected from following a kind of or several combination arbitrarily: sodium lauryl sulphate, Stepanol MG, dodecyl sulfo-sodium succinate, Tween 80;
Described correctives is selected from following a kind of or several combination arbitrarily: aspartame, cyclamate, glycyrrhizin, stevioside, saccharin sodium.
2. fumaric acid tenofovir two pyrrole furan ester dispersible tablets as claimed in claim 1 is characterized in that: the percentage by weight of described fumaric acid tenofovir two pyrrole furan esters, filler, disintegrating agent, lubricant, surfactant and correctives is expressed as follows:
It is one of following that described filler is selected from: the combination of microcrystalline Cellulose 10～35%, lactose 10～40% and mannitol 0～30%, the combination of microcrystalline Cellulose 10～35%, pregelatinized Starch 10～40% and mannitol 0～30%;
Described disintegrating agent is selected from following one or both combination: low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone;
Described lubricant is selected following one or both combination: magnesium stearate, micropowder silica gel;
Described surfactant is a sodium lauryl sulphate;
Described correctives is an aspartame.
3. fumaric acid tenofovir two pyrrole furan ester dispersible tablets as claimed in claim 2 is characterized in that the percentage by weight of described fumaric acid tenofovir two pyrrole furan esters, filler, disintegrating agent, lubricant, surfactant and correctives is expressed as follows:
4. fumaric acid tenofovir two pyrrole furan ester dispersible tablets as claimed in claim 3, it is one of following to it is characterized in that described filler is selected from: the combination of microcrystalline Cellulose 10～25%, lactose 10～25% and mannitol 0～20%, the combination of microcrystalline Cellulose 10～25%, pregelatinized Starch 15～25% and mannitol 0～20%.
5. as the described fumaric acid tenofovir two pyrrole furan ester dispersible tablets of one of claim 1～4, it is characterized in that the acceptable auxiliary element of described pharmacy also comprises binding agent, described binding agent is selected from following a kind of: water, ethanol, ethanol water, amidin, the polyvidone aqueous solution, the polyvidone alcoholic solution, polyvidone ethanol water, hydroxypropyl emthylcellulose aqueous solution, the hydroxypropyl emthylcellulose alcoholic solution, the hydroxypropyl emthylcellulose ethanol water, sodium carboxymethyl cellulose solution, sodium carboxymethyl cellulose alcoholic solution, the sodium carboxymethyl cellulose ethanol water, hydroxypropyl cellulose aqueous solution, hydroxypropyl cellulose alcoholic solution, hydroxypropyl cellulose ethanol water.
6. fumaric acid tenofovir two pyrrole furan ester dispersible tablets as claimed in claim 5 is characterized in that the addition of described binding agent is counted 0.1～0.9ml/g with the gross weight of fumaric acid tenofovir two pyrrole furan esters, filler, disintegrating agent, lubricant, surfactant and correctives.
7. fumaric acid tenofovir two pyrrole furan ester dispersible tablets as claimed in claim 4 is characterized in that the acceptable auxiliary element of described pharmacy is made up of filler, disintegrating agent, lubricant, surfactant and correctives.
8. fumaric acid tenofovir two pyrrole furan ester dispersible tablets as claimed in claim 4, it is characterized in that the acceptable auxiliary element of described pharmacy is made up of filler, disintegrating agent, lubricant, surfactant, correctives and binding agent, described binding agent is selected from following a kind of: mass fraction is that 2～10% amidin, mass fraction are that 2～10% polyvidone aqueous solution, mass fraction are 2～10% hydroxypropyl emthylcellulose aqueous solution; The addition of described binding agent is counted 0.25～0.8ml/g with the gross weight of fumaric acid tenofovir two pyrrole furan esters, filler, disintegrating agent, lubricant, surfactant and correctives.
9. the preparation method of fumaric acid tenofovir two pyrrole furan ester dispersible tablets as claimed in claim 1 comprises the following steps:
1) with fumaric acid tenofovir two pyrrole furan esters, filler, disintegrating agent, correctives, lubricant, the abundant mix homogeneously of surfactant and pulverized 100 mesh sieves;
2) behind the mixing, measure content, tab weight is made sheet.
10. the preparation method of fumaric acid tenofovir two pyrrole furan ester dispersible tablets as claimed in claim 5 is characterized in that the acceptable auxiliary element of described pharmacy also comprises binding agent, and described preparation method comprises the following steps:
A) with fumaric acid tenofovir two pyrrole furan esters, filler and correctives or fumaric acid tenofovir two pyrrole furan esters, filler, correctives and the abundant mix homogeneously of disintegrating agent and pulverized 100 mesh sieves;
B) add binding agent, 20 mesh sieve wet granulations;
C) 50～60 ℃ of dryings are after 2～4 hours, 18 mesh sieve granulate;
D) add lubricant and surfactant or lubricant, surfactant and disintegrating agent again, behind the mixing, measure content, tab weight is made sheet;
In above-mentioned steps (a) and the step (d), one of them step need add disintegrating agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011101411248A CN102198110B (en) | 2011-05-27 | 2011-05-27 | Tenofovir disoproxil fumarate dispersible tablets and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011101411248A CN102198110B (en) | 2011-05-27 | 2011-05-27 | Tenofovir disoproxil fumarate dispersible tablets and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102198110A true CN102198110A (en) | 2011-09-28 |
| CN102198110B CN102198110B (en) | 2012-11-14 |
Family
ID=44659269
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011101411248A Active CN102198110B (en) | 2011-05-27 | 2011-05-27 | Tenofovir disoproxil fumarate dispersible tablets and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102198110B (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103230404A (en) * | 2013-05-14 | 2013-08-07 | 福建广生堂药业股份有限公司 | Novel use of adefovir dipivoxil or medicinal salt thereof |
| CN103330683A (en) * | 2013-06-26 | 2013-10-02 | 神威药业集团有限公司 | Tenofovir disoproxil fumarate fine granules |
| CN103336067A (en) * | 2013-05-29 | 2013-10-02 | 东北制药集团股份有限公司 | High-performance liquid detection method for detecting tenofovir diethyl ester content |
| CN103705478A (en) * | 2013-12-23 | 2014-04-09 | 浙江华海药业股份有限公司 | Oral tablet containing tenofovir disoproxil fumarate |
| CN103830192A (en) * | 2012-11-27 | 2014-06-04 | 安徽贝克生物制药有限公司 | Tenofovir disoproxil fumarate tablets allowing direct powder compression and preparation method thereof |
| CN104739784A (en) * | 2013-12-25 | 2015-07-01 | 辰欣药业股份有限公司 | Method for preparing tenofovir disoproxil fumarate tablet |
| CN105125511A (en) * | 2014-05-30 | 2015-12-09 | 北京星昊医药股份有限公司 | Tenofovir disoproxil fumarate tablet and preparation method thereof |
| CN105213332A (en) * | 2014-06-17 | 2016-01-06 | 广州朗圣药业有限公司 | Oral tablet of a kind of tenofovir disoproxil fumarate and preparation method thereof |
| CN111407736A (en) * | 2020-03-30 | 2020-07-14 | 苏州弘森药业股份有限公司 | Preparation process of tenofovir disoproxil fumarate tablets |
| CN117338733A (en) * | 2023-10-12 | 2024-01-05 | 杭州和泽坤元药业有限公司 | Tenofovir disoproxil fumarate tablet and preparation process thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1738628A (en) * | 2003-01-14 | 2006-02-22 | 吉里德科学公司 | Compositions and methods for combination antiviral therapy |
| CN101199849A (en) * | 2007-12-07 | 2008-06-18 | 北京润德康医药技术有限公司 | Compound for medicine containing nucleoside (acid) and plant extract, preparing method and function thereof |
| CN101229178A (en) * | 2007-11-27 | 2008-07-30 | 北京润德康医药技术有限公司 | Compound medicine compounds containing adefovir dipivoxil, preparing method and uses thereof |
| CN101278938A (en) * | 2008-03-20 | 2008-10-08 | 黑龙江加州国际投资咨询有限公司 | Compound preparation of tenofovir and entecavir and its application against hepatitis B virus |
| CN101781335A (en) * | 2010-03-04 | 2010-07-21 | 福建广生堂药业有限公司 | New tenofovir disoproxil fumarate crystal and preparation method thereof |
-
2011
- 2011-05-27 CN CN2011101411248A patent/CN102198110B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1738628A (en) * | 2003-01-14 | 2006-02-22 | 吉里德科学公司 | Compositions and methods for combination antiviral therapy |
| CN101229178A (en) * | 2007-11-27 | 2008-07-30 | 北京润德康医药技术有限公司 | Compound medicine compounds containing adefovir dipivoxil, preparing method and uses thereof |
| CN101199849A (en) * | 2007-12-07 | 2008-06-18 | 北京润德康医药技术有限公司 | Compound for medicine containing nucleoside (acid) and plant extract, preparing method and function thereof |
| CN101278938A (en) * | 2008-03-20 | 2008-10-08 | 黑龙江加州国际投资咨询有限公司 | Compound preparation of tenofovir and entecavir and its application against hepatitis B virus |
| CN101781335A (en) * | 2010-03-04 | 2010-07-21 | 福建广生堂药业有限公司 | New tenofovir disoproxil fumarate crystal and preparation method thereof |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103830192A (en) * | 2012-11-27 | 2014-06-04 | 安徽贝克生物制药有限公司 | Tenofovir disoproxil fumarate tablets allowing direct powder compression and preparation method thereof |
| CN103230404A (en) * | 2013-05-14 | 2013-08-07 | 福建广生堂药业股份有限公司 | Novel use of adefovir dipivoxil or medicinal salt thereof |
| CN103336067B (en) * | 2013-05-29 | 2015-01-21 | 东北制药集团股份有限公司 | High-performance liquid detection method for detecting tenofovir diethyl ester content |
| CN103336067A (en) * | 2013-05-29 | 2013-10-02 | 东北制药集团股份有限公司 | High-performance liquid detection method for detecting tenofovir diethyl ester content |
| CN103330683A (en) * | 2013-06-26 | 2013-10-02 | 神威药业集团有限公司 | Tenofovir disoproxil fumarate fine granules |
| CN103705478B (en) * | 2013-12-23 | 2020-02-07 | 浙江华海药业股份有限公司 | Oral tablet containing tenofovir disoproxil fumarate |
| CN103705478A (en) * | 2013-12-23 | 2014-04-09 | 浙江华海药业股份有限公司 | Oral tablet containing tenofovir disoproxil fumarate |
| CN104739784A (en) * | 2013-12-25 | 2015-07-01 | 辰欣药业股份有限公司 | Method for preparing tenofovir disoproxil fumarate tablet |
| CN105125511A (en) * | 2014-05-30 | 2015-12-09 | 北京星昊医药股份有限公司 | Tenofovir disoproxil fumarate tablet and preparation method thereof |
| CN105213332A (en) * | 2014-06-17 | 2016-01-06 | 广州朗圣药业有限公司 | Oral tablet of a kind of tenofovir disoproxil fumarate and preparation method thereof |
| CN111407736A (en) * | 2020-03-30 | 2020-07-14 | 苏州弘森药业股份有限公司 | Preparation process of tenofovir disoproxil fumarate tablets |
| CN117338733A (en) * | 2023-10-12 | 2024-01-05 | 杭州和泽坤元药业有限公司 | Tenofovir disoproxil fumarate tablet and preparation process thereof |
| CN117338733B (en) * | 2023-10-12 | 2024-05-28 | 杭州和泽坤元药业有限公司 | Tenofovir disoproxil fumarate tablet and preparation process thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102198110B (en) | 2012-11-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102198110B (en) | Tenofovir disoproxil fumarate dispersible tablets and preparation method thereof | |
| US20070059360A1 (en) | Water-dispersible anti-retroviral pharmaceutical compositions | |
| WO2000078292A1 (en) | Quickly disintegrating solid preparations | |
| CN104490833A (en) | Ezetimibe orally disintegrating tablet and preparation method thereof | |
| CN101138554B (en) | Effervescence dispersible tablet | |
| CN101103980A (en) | Fexofenadine medicinal composition | |
| CN107913256A (en) | A kind of macitentan oral disnitegration tablet for treating pulmonary hypertension and preparation method thereof | |
| KR101562608B1 (en) | Compound chemical medicine acting on respiratory disease, preparation process and use thereof | |
| CN101461788B (en) | Phloroglucine orally disintegrating tablet and preparation method thereof | |
| CN102631329A (en) | Oral paroxetine disintegrating tablet and preparation process thereof | |
| CN102451162A (en) | Olanzapine medicine absorbed through oral mucosa | |
| CN108261399A (en) | Olanzapine oral disnitegration tablet and preparation method thereof | |
| CN104644574A (en) | A sildenafil citrate taste-masking preparation | |
| CN101401795A (en) | Imatinib mesylate orally disintegrating tablets and preparation method thereof | |
| CN101401796A (en) | Pramipexole orally disintegrating tablets and preparation method thereof | |
| CN101011362A (en) | Dispersible tablet of pidotimod and its preparing process and use | |
| KR20230043086A (en) | Oral solid formulation for colon cleansing | |
| CN114129528B (en) | Novel sildenafil citrate preparation with clinical advantages and preparation process and application thereof | |
| CN102626410A (en) | Pharmaceutical composition containing roflumilast | |
| CN111096953A (en) | Preparation method of pregabalin orally disintegrating tablet | |
| CN105213332A (en) | Oral tablet of a kind of tenofovir disoproxil fumarate and preparation method thereof | |
| CN101292977B (en) | Pharmaceutical combination with stable strontium ranelate and its preparations | |
| CN100506237C (en) | Seabuckthorn preparation and its preparing process | |
| AU2013347264B2 (en) | Dispersible tablet | |
| CN102872024A (en) | Misoprostol medicine combination used in mouths |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent for invention or patent application | ||
| CB02 | Change of applicant information |
Address after: 311227 Nanyang Economic Development Zone, Hangzhou, Zhejiang, China, Xiaoshan Applicant after: Hangzhou Coben Pharmaceutical Co., Ltd. Co-applicant after: Jiangsu Branch of the Pharmaceutical Chemical Co., Ltd. Co-applicant after: Hangzhou Coben Pharmaceutical Research Co., Ltd. Address before: 310004, Haihua Plaza, 658 Jianguo North Road, Zhejiang, Hangzhou 17B Applicant before: Hangzhou Coben Pharmaceutical Co., Ltd. Co-applicant before: Jiangsu Branch of the Pharmaceutical Chemical Co., Ltd. Co-applicant before: Hangzhou Coben Pharmaceutical Research Co., Ltd. |
|
| CB03 | Change of inventor or designer information |
Inventor after: Shi Lei Inventor after: You Jinzong Inventor after: Jiang Shanhui Inventor after: Ren Haihua Inventor before: Shi Lei Inventor before: Yu Xiaofen Inventor before: You Jinzong Inventor before: Jiang Shanhui |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: SHI LEI YU XIAOFEN YOU JINZONG JIANG SHANHUI TO: SHI LEI YOU JINZONG JIANG SHANHUI REN HAIHUA |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 311227 Nanyang Economic Development Zone, Hangzhou, Zhejiang, China, Xiaoshan Patentee after: Hangzhou Coben Pharmaceutical Co.,Ltd. Patentee after: Jiangsu Cobain Pharmaceutical Co., Ltd. Patentee after: Hangzhou Coben Pharmaceutical Research Co.,Ltd. Address before: 311227 Nanyang Economic Development Zone, Hangzhou, Zhejiang, China, Xiaoshan Patentee before: Hangzhou Coben Pharmaceutical Co.,Ltd. Patentee before: Jiangsu Coben Medical Chemical Co.,Ltd. Patentee before: Hangzhou Coben Pharmaceutical Research Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20190116 Address after: Room 601, F Building, 1378 Wenyi West Road, Cangqian Street, Yuhang District, Hangzhou City, Zhejiang Province Co-patentee after: Jiangsu Cobain Pharmaceutical Co., Ltd. Patentee after: Hangzhou Kang Kang Pharmaceutical Technology Co., Ltd. Co-patentee after: Hangzhou Coben Pharmaceutical Research Co., Ltd. Address before: 311227 Nanyang Economic Development Zone, Xiaoshan, Hangzhou, Zhejiang Province Co-patentee before: Jiangsu Cobain Pharmaceutical Co., Ltd. Patentee before: Hangzhou Coben Pharmaceutical Co., Ltd. Co-patentee before: Hangzhou Coben Pharmaceutical Research Co., Ltd. |