CN105963268A - 一种乙磺酸尼达尼布分散片及其制备方法 - Google Patents
一种乙磺酸尼达尼布分散片及其制备方法 Download PDFInfo
- Publication number
- CN105963268A CN105963268A CN201610406070.6A CN201610406070A CN105963268A CN 105963268 A CN105963268 A CN 105963268A CN 201610406070 A CN201610406070 A CN 201610406070A CN 105963268 A CN105963268 A CN 105963268A
- Authority
- CN
- China
- Prior art keywords
- sulfonic acid
- nintedanib
- ethyl sulfonic
- dispersible tablet
- acid nintedanib
- 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.)
- Pending
Links
- 229960004378 nintedanib Drugs 0.000 title claims abstract description 50
- XZXHXSATPCNXJR-ZIADKAODSA-N nintedanib Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=CC=CC=1)\NC(C=C1)=CC=C1N(C)C(=O)CN1CCN(C)CC1 XZXHXSATPCNXJR-ZIADKAODSA-N 0.000 title claims abstract description 50
- 239000007919 dispersible tablet Substances 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 title abstract 5
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 31
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 8
- 239000000945 filler Substances 0.000 claims description 7
- 239000011230 binding agent Substances 0.000 claims description 6
- 239000000314 lubricant Substances 0.000 claims description 5
- 238000009702 powder compression Methods 0.000 claims description 5
- 239000004744 fabric Substances 0.000 claims 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 abstract description 10
- 208000036971 interstitial lung disease 2 Diseases 0.000 abstract description 10
- 238000000034 method Methods 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
- 235000009508 confectionery Nutrition 0.000 abstract description 2
- 239000003205 fragrance Substances 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 239000000843 powder Substances 0.000 description 8
- 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 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 238000007907 direct compression Methods 0.000 description 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 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 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 2
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 2
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 2
- HVUMOYIDDBPOLL-UHFFFAOYSA-N 2-(3,4-Dihydroxyoxolan-2-yl)-2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)C1OCC(O)C1O HVUMOYIDDBPOLL-UHFFFAOYSA-N 0.000 description 1
- 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 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 201000003838 Idiopathic interstitial pneumonia Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- 229920001219 Polysorbate 40 Polymers 0.000 description 1
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- ZNMRDZZRAFJOKY-UHFFFAOYSA-N ethanesulfonic acid methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate Chemical compound CCS(=O)(=O)O.CN1CCN(CC1)CC(=O)N(C)C2=CC=C(C=C2)N=C(C3=CC=CC=C3)C4=C(NC5=C4C=CC(=C5)C(=O)OC)O ZNMRDZZRAFJOKY-UHFFFAOYSA-N 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000011354 first-line chemotherapy Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 1
- 229940015847 ofev Drugs 0.000 description 1
- 230000003950 pathogenic mechanism Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 229940101027 polysorbate 40 Drugs 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
- 230000002265 prevention Effects 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 230000009325 pulmonary function Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 229960003010 sodium sulfate Drugs 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种乙磺酸尼达尼布分散片剂,用于治疗特发性肺纤维化(IPF),以乙磺酸尼达尼布为原料,加入辅料,制备成乙磺酸尼达尼布分散片。崩解快、吸收快、生物利用度高;服用方便;肠道残留少,副作用少;味甜且有香气,特别容易提高患者服药依从性,改善制剂的口感,且在压片过程中不会出现粘冲现象,有利于实现工业化生产。
Description
技术领域
本发明涉及一种乙磺酸尼达尼布新剂型,特别涉及的是乙磺酸尼达尼布分散片及其制备方法。
背景技术
尼达尼布(Nintedanib)是勃林格殷格翰公司开发的一种口服三联血管激酶抑制剂,2014年10月经FDA批准 OFEV® (尼达尼布) 用于治疗特发性肺纤维化 (IPF),成为首个获准用于治疗IPF的 酪氨酸激酶抑制剂 (TKI) 。尼达尼布(Nintedanib)针对已被证实在肺纤维化病理机制中具有潜在影响的生长因子受体发挥作用,其中最为重要的就是血小板源性生长因子受体(PDGFR)、成纤维细胞生长因子受体(FGFR)和血管内皮生长因子受体(VEGFR)。通过阻断这些参与纤维化进程的信号转导通路,尼达尼布(Nintedanib)能够通过减少肺功能下降速度、从而减缓IPF疾病进展。特发性肺纤维化是一种病因不明,以肺部的进行性纤维化损害为特征的慢性进展性疾病,是最为常见的特发性间质性肺炎 。目前尚无预防方法或除肺移植外国际公认的有确切疗效的治疗方法。该在全球范围的患病率达到14-43例/每100000人 。据此估算我国现有的特发性肺纤维化患者在60万人左右。2014年6月EMA宣布尼达尼布(Nintedanib)治疗特发性肺纤维化(IPF)的上市许可申请获得确认、并被EMA纳入加速审批名单。9月欧盟宣布尼达尼布(Nintedanib)联合多西他赛在一线化疗之后应用于组织学诊断为腺癌的、局部晚期或转移性或局部复发性非小细胞肺癌(NSCLC)成年患者的支持性意见。公司目前还在针对尼达尼布(Nintedanib)作为癌症治疗选择开展临床研发工作,包括非小细胞肺癌、卵巢癌、结直肠癌和肝细胞肝癌。
分散片是近年来发展起来的一种速效制剂,由于其特有的优势,已越来越受到人们的关注。可以加入增溶剂;可以提高乙磺酸尼达尼布难溶性药物的溶出度,适合于服用。对于崩解困难的药物制成片可有利于吸收。片的特点:①崩解快、吸收快、生物利用度高;②服用方便 ③肠道残留少,副作用少。
发明内容
本发明的目的是提供一种乙磺酸尼达尼布分散片及其制备方法。
本发明目的通过如下技术方案来实现。
本发明乙磺酸尼达尼布分散片由如下成分组成(重量百分比):
乙磺酸尼达尼布 | 20-60% |
填充剂 | 5-30% |
崩解剂 | 10-25% |
粘合剂 | 0.1-6% |
增溶剂 | 0.1-6% |
润滑剂 | 0.5-5%。 |
以上为本发明基本处方,可以根据实际需要进行适当调节和删减。
乙磺酸尼达尼布是活性成分,优选含量范围10-40%,进一步优选范围10-30%。单位制剂中乙磺酸尼达尼布剂量50-150mg,优选剂量为50-150mg,更优选的剂量为50、100、150mg。
由于分散片要求在水中可迅速崩解均匀分散,具有服用方便、崩解迅速、吸收快和生物利用度高等特点。因此对辅料种类及其性能的选择是制备片的关键。发明人经过多次试验,确定了适合乙磺酸尼达尼布分散片的药用辅料及其用量。
填充剂选择用来增加片的重量和体积,以便于制剂的成型和分剂量。本发明中填充剂选自乳糖、蔗糖、微晶纤维素、预胶化淀粉、糊精等中的一种或几种的混合物。用量范围优选10-30%,特别优选15-25%。
崩解剂选自低取代羟丙纤维素、交联聚维酮等药用辅料。用量优选10-25%,特别优选15-20%。
增溶剂的种类和用量的选择对于本制剂溶出至关重要。本发明的增溶剂选十二烷基硫酸钠、聚乙二醇6000、聚乙二醇4000、吐温80、吐温40、司盘60、司盘40中之一或其中几种的混合物,进一步掩盖了乙磺酸尼达尼布的不良怪味,改善了片的口感。
润滑剂选自微粉硅胶、硬脂酸镁、滑石粉中的一种或几种的混合物。
本发明还提供了乙磺酸尼达尼布分散片的制备方法。本发明乙磺酸尼达尼布分散片可以粉末直接压片法制备。粉末直接压片法制备步骤是:将乙磺酸尼达尼布与填充剂(例如乳糖)、崩解剂、增溶剂、粘合剂和润滑剂混合均匀后,粉末直接压片。
本发明乙磺酸尼达尼布分散片崩解快、吸收快、生物利用度高;服用方便;肠道残留少,副作用少;味甜,没有乙磺酸尼达尼布特殊臭味且有香气,特别容易提高患者服药依从性。
具体实施方式
实施例l
处方:
制备方法:
(1)将乙磺酸尼达尼布粉末(200目)与蔗糖粉(150目)等量递增混合均匀,得混合物A;
(2)将剩余的辅料过200目筛后,等量递增混合均匀,得混合物B;
(3)将混合物A和混合物B按等量递增法混合均匀后,直接压片即可。
实施例2
处方:
制备方法:
(1)将乙磺酸尼达尼布粉末(200目)与乳糖粉(150目)等量递增混合均匀,得混合物A;
(2)将剩余的辅料过200目筛后,等量递增混合均匀,得混合物B;
(3)将混合物A和混合物B按等量递增法混合均匀后,直接压片即可。
实施例3
处方:
制备方法:
(1)将乙磺酸尼达尼布粉末(200目)与乳糖粉(150目)等量递增混合均匀,得混合物A;
(2)将剩余的辅料过200目筛后,等量递增混合均匀,得混合物B;
(3)将混合物A和混合物B按等量递增法混合均匀后,直接压片即可。
实施例4
处方:
制备方法:
(1)将乙磺酸尼达尼布粉末(200目)与乳糖粉(150目)等量递增混合均匀,得混合物A;
(2)将剩余的辅料过200目筛后,等量递增混合均匀,得混合物B;
(3)将混合物A和混合物B按等量递增法混合均匀后,直接压片即可。
发明处方工艺制备样品的稳定性考察:
将实施例1、实施例2、实施例3和实施例4制备的样品分别放置于稳定性试验箱内,设置温度在40℃、相对湿度75%RH条件下进行三个月加速考察;
以崩解时限作为考察指标,证明所发明的片处方工艺的科学性;
以上实施例所用乙磺酸尼达尼布原料为辉瑞药业生产;辅料供应厂家为卡乐康制药、德固赛制药、乐嘉文制药、国际特品制药有限公司及淮南山河制药有限公司。
Claims (8)
1.一种乙磺酸尼达尼布分散片,由如下重量百分比成分组成:
2.根据权利要求1所述的乙磺酸尼达尼布分散片,其中所述乙磺酸尼达尼布含量范围20-60%。
3.根据权利要求1所述的乙磺酸尼达尼布分散片,其中所述填充剂用量范围5-20%。
4.根据权利要求1所述的乙磺酸尼达尼布分散片,其中所述崩解剂用量15-20%。
5.根据权利要求1所述的乙磺酸尼达尼布分散片,其中所述粘合剂用量0.5-2%。
6.根据权利要求2-5中任一权利要求所述的乙磺酸尼达尼布分散片,其中:乙磺酸尼达尼布含量范围20-50%;填充剂用量5-20%;崩解剂用量15-20%;粘合剂用量0.5-2%,增溶剂用量0.5-2%。
7.根据权利要求1所述的乙磺酸尼达尼布分散片,其中所述乙磺酸尼达尼布单位剂量50-150mg。
8.权利要求1所述乙磺酸尼达尼布分散片的制备方法,采用粉末直接压片法,将乙磺酸尼达尼布与填充剂、崩解剂、增溶剂、粘合剂和润滑剂混合均匀后,粉末直接压片。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610406070.6A CN105963268A (zh) | 2016-06-12 | 2016-06-12 | 一种乙磺酸尼达尼布分散片及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610406070.6A CN105963268A (zh) | 2016-06-12 | 2016-06-12 | 一种乙磺酸尼达尼布分散片及其制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN105963268A true CN105963268A (zh) | 2016-09-28 |
Family
ID=57010987
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610406070.6A Pending CN105963268A (zh) | 2016-06-12 | 2016-06-12 | 一种乙磺酸尼达尼布分散片及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105963268A (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108144069A (zh) * | 2016-12-02 | 2018-06-12 | 广东东阳光药业有限公司 | 一种尼达尼布包合物、制剂及其制备方法 |
WO2020079706A1 (en) | 2018-10-15 | 2020-04-23 | Cipla Limited | Pharmaceutical formulation |
CN111973596A (zh) * | 2020-06-15 | 2020-11-24 | 深圳市泰力生物医药有限公司 | 具有改良溶出性质的抗肺纤维化组合物 |
CN112891558A (zh) * | 2021-02-08 | 2021-06-04 | 浙江工业大学 | 一种尼达尼布超分子共载包合物 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104844499A (zh) * | 2015-06-05 | 2015-08-19 | 北京康立生医药技术开发有限公司 | 一锅法制备尼达尼布的合成方法 |
CN105001143A (zh) * | 2015-07-24 | 2015-10-28 | 南京正大天晴制药有限公司 | 一种制备高纯度乙磺酸尼达尼布的方法 |
-
2016
- 2016-06-12 CN CN201610406070.6A patent/CN105963268A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104844499A (zh) * | 2015-06-05 | 2015-08-19 | 北京康立生医药技术开发有限公司 | 一锅法制备尼达尼布的合成方法 |
CN105001143A (zh) * | 2015-07-24 | 2015-10-28 | 南京正大天晴制药有限公司 | 一种制备高纯度乙磺酸尼达尼布的方法 |
Non-Patent Citations (1)
Title |
---|
元英进主编: "《现代制药工艺学 下册》", 31 January 2006, 化学工业出版社 * |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108144069A (zh) * | 2016-12-02 | 2018-06-12 | 广东东阳光药业有限公司 | 一种尼达尼布包合物、制剂及其制备方法 |
CN108144069B (zh) * | 2016-12-02 | 2024-02-23 | 广东东阳光药业股份有限公司 | 一种尼达尼布包合物、制剂及其制备方法 |
WO2020079706A1 (en) | 2018-10-15 | 2020-04-23 | Cipla Limited | Pharmaceutical formulation |
CN111973596A (zh) * | 2020-06-15 | 2020-11-24 | 深圳市泰力生物医药有限公司 | 具有改良溶出性质的抗肺纤维化组合物 |
CN111973596B (zh) * | 2020-06-15 | 2022-02-15 | 深圳市泰力生物医药有限公司 | 具有改良溶出性质的抗肺纤维化组合物 |
CN112891558A (zh) * | 2021-02-08 | 2021-06-04 | 浙江工业大学 | 一种尼达尼布超分子共载包合物 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105963268A (zh) | 一种乙磺酸尼达尼布分散片及其制备方法 | |
CN101647797B (zh) | 一种含有苯磺酸氨氯地平和缬沙坦的药物组合物及其制备方法 | |
CN104887641B (zh) | 帕布昔利布胃漂浮片及其制备方法 | |
CN106074406A (zh) | 一种富马酸沃诺拉赞分散片及其制备方法 | |
CN104042577A (zh) | 一种稳定的托匹司他片及其制备方法 | |
CN105997911A (zh) | 一种奥拉帕尼分散片及其制备方法 | |
CN105902507A (zh) | 一种乙磺酸尼达尼布制剂及其应用 | |
Chavhan et al. | Design and evaluation of once daily sustained release matrix tablets of nicorandil | |
CN104434826B (zh) | 一种瑞舒伐他汀钙分散片 | |
CN103083273A (zh) | 甲磺酸伊马替尼片芯、包衣片及其制备方法 | |
CN101632644B (zh) | 厄贝沙坦分散片及其制备方法 | |
CN104013589A (zh) | 一种阿西替尼口腔崩解片及其制备方法 | |
JPWO2017047586A1 (ja) | 錠剤 | |
CN108125913A (zh) | 一种索非布韦药物制剂 | |
CN104138380A (zh) | 厄洛替尼或其可药用盐的组合物及其制备方法和用途 | |
CN104398482B (zh) | 应用复合乳糖的吲达帕胺缓释药物 | |
CN108721238A (zh) | 一种碳酸锂缓释片 | |
CN104274420B (zh) | 一种达沙替尼组合物及其制备方法 | |
CN104706614B (zh) | 坦度螺酮微孔渗透泵制剂 | |
CN104414988B (zh) | 一种达沙替尼片剂及其制备工艺 | |
WO2017004733A1 (zh) | 一种人参皂苷c-k口服固体制剂及其制备方法 | |
CN113750059B (zh) | 一种迈华替尼片剂及其制备方法 | |
CN104840442B (zh) | 一种含有富马酸喹硫平的缓释片剂及其制备方法 | |
CN107998087A (zh) | 一种非布司他分散片及其制备方法 | |
CN104434850B (zh) | 一种含有阿德福韦酯的口服固体药物组合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
WD01 | Invention patent application deemed withdrawn after publication | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160928 |