CN107530292A - 瑞博西尼片剂 - Google Patents
瑞博西尼片剂 Download PDFInfo
- Publication number
- CN107530292A CN107530292A CN201680022122.8A CN201680022122A CN107530292A CN 107530292 A CN107530292 A CN 107530292A CN 201680022122 A CN201680022122 A CN 201680022122A CN 107530292 A CN107530292 A CN 107530292A
- Authority
- CN
- China
- Prior art keywords
- tablet
- xini
- sweden
- china
- rui boxini
- 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
- 239000003826 tablet Substances 0.000 claims abstract description 114
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 239000003814 drug Substances 0.000 claims abstract description 11
- 229940079593 drug Drugs 0.000 claims abstract description 11
- 239000007935 oral tablet Substances 0.000 claims abstract description 9
- 229940096978 oral tablet Drugs 0.000 claims abstract description 9
- 150000003890 succinate salts Chemical class 0.000 claims description 17
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 14
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 13
- 238000000576 coating method Methods 0.000 abstract description 54
- 239000011248 coating agent Substances 0.000 abstract description 45
- 239000000203 mixture Substances 0.000 description 17
- 239000000463 material Substances 0.000 description 13
- 238000000034 method Methods 0.000 description 8
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 7
- 239000008108 microcrystalline cellulose Substances 0.000 description 7
- 229940016286 microcrystalline cellulose Drugs 0.000 description 7
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 7
- 239000008186 active pharmaceutical agent Substances 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 229940088679 drug related substance Drugs 0.000 description 6
- 239000007916 tablet composition Substances 0.000 description 6
- 239000007888 film coating Substances 0.000 description 5
- 238000009501 film coating Methods 0.000 description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 5
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 4
- RHXHGRAEPCAFML-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1N1CCNCC1 RHXHGRAEPCAFML-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229950003687 ribociclib Drugs 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 description 2
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000008351 acetate buffer Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000005336 cracking Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000000314 lubricant Substances 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
- 239000008363 phosphate buffer Substances 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 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
- 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 1
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
- 108010025454 Cyclin-Dependent Kinase 5 Proteins 0.000 description 1
- 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 description 1
- 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 description 1
- 101710106279 Cyclin-dependent kinase 1 Proteins 0.000 description 1
- 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 1
- 102100036329 Cyclin-dependent kinase 3 Human genes 0.000 description 1
- 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 1
- 102100026804 Cyclin-dependent kinase 6 Human genes 0.000 description 1
- 102100024457 Cyclin-dependent kinase 9 Human genes 0.000 description 1
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 1
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 1
- 102100026805 Cyclin-dependent-like kinase 5 Human genes 0.000 description 1
- 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 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 101000715946 Homo sapiens Cyclin-dependent kinase 3 Proteins 0.000 description 1
- 101000980930 Homo sapiens Cyclin-dependent kinase 9 Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 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 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229920002892 amber Polymers 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- -1 hydroxypropyl methyl Chemical group 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 238000003475 lamination Methods 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 239000003595 mist Substances 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
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- HKSQZEGSMBFHGC-UHFFFAOYSA-N pyrimidine-4-carboxamide Chemical class NC(=O)C1=CC=NC=N1 HKSQZEGSMBFHGC-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 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
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
-
- 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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明关于瑞博西尼包括其盐的口服片剂。本发明的一个实施方式关于具有高载药量与即释曲线的瑞博西尼片剂。本发明的一个实施方式关于瑞博西尼的包衣片剂。本发明的另一实施方式关于瑞博西尼的包衣片剂,其中所述包衣是先进的防潮包衣(例如
Description
技术领域
本发明关于瑞博西尼(ribociclib)和/或其药学上可接受盐的片剂制剂,以及使用其进行治疗的方法。
背景技术
式(I)的化合物
已知是瑞博西尼。其化学名称为7-环戊基-N,N-二甲基-2-{[5-(哌嗪-1-基)吡啶-2-基]氨基}-7H-吡咯并[2,3-d]嘧啶-6-甲酰胺,且其合成具体描述于WO 2010/020675 A1的实施例74中。
瑞博西尼的琥珀酸盐由式(II)描述:
且描述于WO2012/064805中。
瑞博西尼和其药学上可接受盐具有有价值的药理学特性,且可例如被用作(1)细胞周期蛋白依赖性激酶(尤其是选自CDK1、CDK2、CDK3、CDK4、CDK5、CDK6和CDK9的细胞周期蛋白依赖性激酶)的抑制剂;和(2)糖原合成酶激酶-3(GSK-3)的调节剂和/或抑制剂。
瑞博西尼也以代码名称LEE011已知。
发明概述
本发明关于瑞博西尼(包括其盐和/或溶剂合物)的口服制剂。本发明的一个实施方式关于具有高载药量与即释曲线的瑞博西尼的片剂制剂。本发明的一个实施方式关于瑞博西尼的包衣片剂制剂。本发明的另一实施方式关于瑞博西尼的包衣片剂制剂,其中该包衣为先进的防潮包衣(例如amb II包衣,其中该包衣是以PVA为基础)。
附图说明
参考以下所描述的附图来说明本发明。
图1A和1B描绘制备瑞博西尼片剂的工艺流程图。未包衣片剂根据步骤1-8制备。包衣片剂根据步骤1-9制备。
图2展示采用(基于标准HPMC)和用amb II(基于PVA的先进防潮(AMB)包衣)制备的片剂图片。
图3展示采用标准和amb II包衣的瑞博西尼片剂的动态湿气吸附(DVS)数据。
图4展示通过100rpm的转篮和在37℃下具有不同pH值的溶解介质所获得的采用amb II包衣的瑞博西尼(LEE011)片剂的溶解曲线。
发明详述
本发明关于一种瑞博西尼或其药学上可接受盐的固体口服片剂剂型。该制剂具有良好的工艺性能和高稳定性。
本发明的片剂具有即释曲线。在处于标准溶解测试下45分钟后,这些片剂释放至少75%(Q)(其中Q是指由USP第<711>章定义的接受准则)的活性成分。在实施方式中,当使用100rpm的转篮且在37℃下以900ml的HCl pH 1作为溶解介质时,45分钟后片剂释放至少75%的活性成分。在另一实施方式中,当使用100rpm的转篮且在37℃下以900ml的HCl pH 2作为溶解介质时,45分钟后片剂释放至少75%的活性成分。在另一实施方式中,当使用100rpm的转篮且在37℃下以900ml的乙酸盐缓冲液pH 4.5作为溶解介质时,45分钟后片剂释放至少75%的活性成分。在另一实施方式中,当在37℃下使用100rpm的转篮且以900ml的磷酸盐缓冲液pH 6.8作为溶解介质时,45分钟后片剂释放至少75%的活性成分。
本发明的片剂可以是包衣的或未包衣的。
本发明片剂具有以核心片剂中瑞博西尼琥珀酸盐的w/w百分比进行测量时,至少40%、45%、50%、55%或60%的高载药量。
本发明片剂具有以核心片剂中瑞博西尼游离碱的w/w百分比进行测量时,至少32%、40%、44%、47%或52%的高载药量。
瑞博西尼琥珀酸盐的重量比(w/w)为核心片剂的至少40%。在一个实施方式中,瑞博西尼琥珀酸盐的重量比(w/w)为核心片剂的至少50%。在另一实施方式中,瑞博西尼琥珀酸盐的重量比(w/w)为核心片剂的至少55%。在另一实施方式中,瑞博西尼琥珀酸盐的重量比(w/w)为核心片剂的约55%至65%。在另一实施方式中,瑞博西尼琥珀酸盐的重量比(w/w)为核心片剂的约60%。
当就瑞博西尼游离碱来进行测量时,瑞博西尼的重量比(w/w)为核心片剂的至少32%。在一个实施方式中,瑞博西尼的重量比(w/w)为核心片剂的至少40%。在另一实施方式中,瑞博西尼的重量比(w/w)为核心片剂的至少44%。在另一实施方式中,瑞博西尼的重量比(w/w)为核心片剂的约44%至52%。在另一实施方式中,瑞博西尼的重量比(w/w)为核心片剂的约47%。
核心片剂也称作“片剂核心”。
在未包衣片剂中,片剂核心为整个片剂。在包衣片剂中,片剂核心为片剂排除包衣的部分。
根据本发明的片剂制剂可含有常用于药物制剂中的药学上可接受赋形剂,尤其例如用于口服施用的赋形剂,如填充剂、黏合剂、崩解剂和润滑剂。
填充剂例如可单独为纤维素、甘露醇、磷酸二钙、乳糖、微晶纤维素或其组合。
黏合剂例如可单独为羟丙基纤维素、聚乙烯吡咯烷酮或其组合。
崩解剂例如可单独为交联聚乙烯吡咯烷酮、交联羧甲基纤维素钠、低取代羟丙基纤维素、羟基乙酸淀粉钠或其组合。
润滑剂例如可单独为硬脂酸镁、硬脂酸、滑石、二氧化硅、硬脂酰富马酸钠或其组合。
举例而言,附图1A和1B展示制备瑞博西尼片剂的工艺流程图。未包衣片剂是根据步骤1-8制备。包衣片剂是根据步骤1-9制备。
在一个实施方式中,核心瑞博西尼片剂具有内相和外相,该内相包含瑞博西尼或其盐。
包衣材料:
本发明的瑞博西尼片剂为即释片剂且可采用任何即释的包衣材料包衣。例如包衣材料可为200、amb II、fxTM、II、或其混合物。200、amb II、fxTM、II和都可购自Colorcon,Inc。
在一个实施方式中,包衣材料为是HPMC(羟丙基甲基纤维素)包衣材料且具有下列组成:HPMC(Pharmacoat 603)71.4%、聚乙二醇7.15%、滑石7.15%和氧化铁14.3%。
在另一实施方式中,包衣材料为amb II。amb II是以PVA(聚乙烯醇)为基础的包衣材料且具有下列组成:聚乙烯醇45.52%、氧化铁32%、滑石20%、卵磷脂(大豆)2%和三仙胶0.48%。
当瑞博西尼片剂采用amb II包衣时,该片剂显示改良的外观且基本上没有开裂缺陷。
本发明在以下实施例中进一步描述。下列非限制性实施例说明本发明且不视为限制所附权利要求书的范围。
实施例1未包衣的50mg和200mg瑞博西尼片剂
下表1详述未包衣的50mg和200mg瑞博西尼片剂的组成。这些片剂是根据工艺流程图(图1A-1B)的步骤1-8制备。
表1.每剂型单位的组成
1盐因子为1.272。若药物物质含量为≤99.5%,其量增加,并相应减少微晶纤维素含量。
2植物来源
实施例2未包衣的100mg、150mg和300mg瑞博西尼片剂
下表2详述未包衣的100mg、150mg和300mg瑞博西尼片剂的组成。这些片剂根据工艺流程图(图1A-1B)的步骤1-8制备。
表2.每剂型单位的组成
1盐因子为1.272。若药物物质含量为≤99.5%,其量增加,并相应减少微晶纤维素含量。
2植物来源
实施例3(采用amb II包衣)包衣的50mg和200mg瑞博西尼片剂
下表3详述薄膜包衣的50mg和200mg瑞博西尼片剂的组成。这些片剂根据工艺流程图(图1A-1B)的步骤1-9制备。包衣材料为amb II,其为市售可得的且是以PVA为基础的先进防潮(AMB)包衣。
表3.每剂型单位的组成
1盐因子为1.272。若药物物质含量为≤99.5%,其量增加,并相应减少微晶纤维素含量。
2植物来源
3制备过量包衣以补偿包衣过程期间的损耗
4该包衣预混物为市售可得产品
5在加工期间去除
实施例4(采用amb II包衣)包衣的100mg、150mg和300mg瑞博西尼片剂
下表4详述薄膜包衣的100mg、150mg和300mg瑞博西尼片剂的组成。这些片剂根据工艺流程图(图1A-1B)的步骤1-9制备。包衣材料为ambII,其为市售可得的且是以PVA为基础的先进防潮(AMB)包衣。
表4.每剂型单位的组成
1盐因子为1.272。若药物物质含量为≤99.5%,其量增加,并相应减少微晶纤维素含量。
2植物来源
3制备过量包衣以补偿包衣过程期间的损耗
4包衣预混物为市售可得产品
5在加工期间去除
实施例5
比较采用不同包衣((基于标准HPMC)相比amb II(基于PVA的先进防潮(AMB)包衣材料))包衣的瑞博西尼片剂。在Bohle包衣机(1Kg规模)中以3g/min的喷雾速率进行包衣。用标准包衣时观察到片剂标识桥接问题和片剂开裂的缺陷。相比之下,用以PVA为基础的amb II包衣的片剂并未观察到开裂。
图2展示采用(基于标准HPMC)和采用amb II(基于PVA的先进防潮(AMB)包衣材料)制备的片剂的图像。
实施例6
采用标准和amb II包衣的瑞博西尼片剂的动态湿气吸附(DVS)数据显示于图3中。在50mg和200mg剂量单位下,与标准片剂相比,采用AMB包衣(amb II)包衣的片剂展示出更好的性能。
实施例7
在不同pH值的介质中评估采用amb II包衣的瑞博西尼片剂的溶解曲线。装置:离心篮,旋转:100rpm,体积:900mL,介质:HCl pH 1、HCl pH 2、乙酸盐缓冲液pH 4.5、磷酸盐缓冲液pH 6.8。图4展示在不同pH值的介质中,采用amb II薄膜包衣的瑞博西尼片剂的溶解曲线。
实施例8采用不同包衣预混物组合的(amb II包衣)包衣的50mg和200mg瑞博西尼片剂
下表5详述相比于实施例3,采用不同包衣预混物组合的薄膜包衣的50mg和200mg瑞博西尼片剂的组成。这些片剂根据工艺流程图(图1A-1B)的步骤1-9制备。包衣材料为amb II,其为市售可得的且是以PVA为基础的先进防潮(AMB)包衣。
表5.每剂型单位的组成
1盐因子为1.272。若药物物质含量为≤99.5%,其量增加,并相应减少微晶纤维素含量。
2植物来源
3制备过量包衣以补偿包衣过程期间的损耗
4包衣预混物为市售可得产品
5在加工期间去除
实施例9不同包衣预混物组合的(采用amb II包衣)包衣的100mg、150mg和300mg瑞博西尼片剂
下表6详述相比于实施例4,采用不同包衣预混物组合的薄膜包衣的100mg、150mg和300mg瑞博西尼片剂的组成。这些片剂根据工艺流程图(图1A-1B)的步骤1-9制备。包衣材料为amb II,其为市售可得的且是以PVA为基础的先进防潮(AMB)包衣。
表6.每剂型单位的组成
1盐因子为1.272。若药物物质含量为≤99.5%,其量增加,并相应减少微晶纤维素含量。
2植物来源
3制备过量包衣以补偿包衣过程期间的损耗
4包衣预混物为市售可得产品
5在加工期间去除
Claims (26)
1.一种药物口服片剂,其包含瑞博西尼或其药学上可接受盐。
2.如权利要求1的片剂,其包含瑞博西尼琥珀酸盐。
3.如权利要求1的片剂,其包含瑞博西尼或其盐,其中当根据USP<711>在37℃下以100rpm的转篮和900ml pH 2或pH 4.5的溶解介质测试时,45分钟后所述片剂释放至少75%的该瑞博西尼或其盐。
4.如权利要求1的片剂,其在片剂核心中包含瑞博西尼或其盐,其中就瑞博西尼游离碱进行测量时,所述片剂核心包含至少32%重量比(w/w)的瑞博西尼。
5.如权利要求4的片剂,其中瑞博西尼的重量比(w/w)为所述片剂核心的至少40%。
6.如权利要求5的片剂,其中瑞博西尼的重量比(w/w)为所述片剂核心的至少44%。
7.如权利要求6的片剂,其中瑞博西尼的重量比(w/w)为所述片剂核心的约44%至52%。
8.如权利要求4的片剂,其中瑞博西尼的重量比(w/w)为所述片剂核心的约47%。
9.一种包含瑞博西尼琥珀酸盐的药物口服片剂,其中瑞博西尼琥珀酸盐的重量比(w/w)为片剂核心的至少40%。
10.如权利要求9的片剂,其中瑞博西尼琥珀酸盐的重量比(w/w)为所述片剂核心的至少50%。
11.如权利要求10的片剂,其中瑞博西尼琥珀酸盐的重量比(w/w)为所述片剂核心的至少55%。
12.如权利要求11的片剂,其中瑞博西尼琥珀酸盐的重量比(w/w)为所述片剂核心的约55%至65%。
13.如权利要求9的片剂,其中瑞博西尼的重量比(w/w)为所述片剂核心的约60%。
14.一种包衣药物口服片剂,其包含瑞博西尼或其药学上可接受盐,其中所述包衣包含聚乙烯醇(PVA)。
15.一种包衣药物口服片剂,其包含瑞博西尼琥珀酸盐,其中所述包衣包含PVA。
16.一种包含瑞博西尼或其盐的包衣药物口服片剂,其中当根据USP<711>在37℃下以100rpm的转篮和900ml pH 2或pH 4.5的溶解介质测试时,45分钟后所述片剂释放至少75%的所述瑞博西尼或其盐,且其中所述包衣包含PVA。
17.一种包含瑞博西尼或其盐的包衣药物口服片剂,其中就瑞博西尼游离碱来进行测量时,瑞博西尼的重量比(w/w)为所述片剂核心的至少32%,且其中所述包衣包含PVA。
18.如权利要求17的片剂,其中瑞博西尼的重量比(w/w)为所述片剂核心的至少40%。
19.如权利要求18的片剂,其中瑞博西尼的重量比(w/w)为所述片剂核心的至少44%。
20.如权利要求19的片剂,其中瑞博西尼的重量比(w/w)为所述片剂核心的约44%至52%。
21.如权利要求17的片剂,其中瑞博西尼的重量比(w/w)为所述片剂核心的约47%。
22.一种包含瑞博西尼琥珀酸盐的包衣药物口服片剂,其中瑞博西尼琥珀酸盐的重量比(w/w)为所述片剂核心的至少40%。
23.如权利要求22的片剂,其中瑞博西尼琥珀酸盐的重量比(w/w)为所述片剂核心的至少50%。
24.如权利要求23的片剂,其中瑞博西尼琥珀酸盐的重量比(w/w)为所述片剂核心的至少55%。
25.如权利要求24的片剂,其中瑞博西尼琥珀酸盐的重量比(w/w)为所述片剂核心的约55%至65%。
26.如权利要求22的片剂,其中瑞博西尼的重量比(w/w)为所述片剂核心的约60%。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211237232.XA CN115554257A (zh) | 2015-04-16 | 2016-04-14 | 瑞博西尼片剂 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562148240P | 2015-04-16 | 2015-04-16 | |
US62/148,240 | 2015-04-16 | ||
PCT/IB2016/052136 WO2016166703A1 (en) | 2015-04-16 | 2016-04-14 | Ribociclib tablet |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202211237232.XA Division CN115554257A (zh) | 2015-04-16 | 2016-04-14 | 瑞博西尼片剂 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN107530292A true CN107530292A (zh) | 2018-01-02 |
CN107530292B CN107530292B (zh) | 2022-11-01 |
Family
ID=55806565
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202211237232.XA Pending CN115554257A (zh) | 2015-04-16 | 2016-04-14 | 瑞博西尼片剂 |
CN201680022122.8A Active CN107530292B (zh) | 2015-04-16 | 2016-04-14 | 瑞博西尼片剂 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202211237232.XA Pending CN115554257A (zh) | 2015-04-16 | 2016-04-14 | 瑞博西尼片剂 |
Country Status (29)
Country | Link |
---|---|
US (3) | US10799506B2 (zh) |
EP (2) | EP4197530A1 (zh) |
JP (1) | JP2018514523A (zh) |
KR (1) | KR20170137101A (zh) |
CN (2) | CN115554257A (zh) |
AR (1) | AR104257A1 (zh) |
AU (3) | AU2016248017A1 (zh) |
BR (1) | BR112017021283A2 (zh) |
CA (1) | CA2982425C (zh) |
CL (1) | CL2017002593A1 (zh) |
CO (1) | CO2017010510A2 (zh) |
DK (1) | DK3283058T3 (zh) |
EA (1) | EA201792290A1 (zh) |
EC (1) | ECSP17075052A (zh) |
ES (1) | ES2938261T3 (zh) |
FI (1) | FI3283058T3 (zh) |
HR (1) | HRP20230053T1 (zh) |
HU (1) | HUE061213T2 (zh) |
IL (1) | IL254818A0 (zh) |
MX (1) | MX2017013350A (zh) |
PE (1) | PE20180035A1 (zh) |
PH (1) | PH12017501820A1 (zh) |
PL (1) | PL3283058T3 (zh) |
PT (1) | PT3283058T (zh) |
SG (1) | SG11201708084PA (zh) |
SI (1) | SI3283058T1 (zh) |
TN (1) | TN2017000422A1 (zh) |
TW (1) | TW201642864A (zh) |
WO (1) | WO2016166703A1 (zh) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP4197530A1 (en) | 2015-04-16 | 2023-06-21 | Novartis AG | Ribociclib tablet |
CA3048036A1 (en) | 2018-07-02 | 2020-01-02 | Apotex Inc | Novel crystalline form of ribociclib succinate |
US20230044749A1 (en) | 2019-12-16 | 2023-02-09 | Lunella Biotech, Inc. | Selective cdk 4/6 inhibitor cancer therapeutics |
EP4077331A4 (en) | 2019-12-16 | 2023-12-27 | Lunella Biotech, Inc. | SELECTIVE CDK4/6 INHIBITOR CANCER THERAPEUTICS |
US20230310327A1 (en) * | 2020-08-03 | 2023-10-05 | Natco Pharma Limited | Pharmaceutical compositions comprising ribociclib |
WO2022162122A1 (en) | 2021-01-29 | 2022-08-04 | Biotx.Ai Gmbh | Genetically verified netosis inhibitor for use in the treatment of a sars-cov2 infection |
WO2023144684A1 (en) | 2022-01-25 | 2023-08-03 | Novartis Ag | Ribociclib pharmaceutical compositions |
WO2024049926A1 (en) | 2022-08-31 | 2024-03-07 | Arvinas Operations, Inc. | Dosage regimens of estrogen receptor degraders |
WO2024115680A1 (en) | 2022-12-01 | 2024-06-06 | Krka, D.D., Novo Mesto | Ribociclib salts and formulations thereof |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1157002A (zh) * | 1994-07-12 | 1997-08-13 | 伯温德药品服务公司 | 隔潮膜涂层组合物及其生产方法以及涂层制品 |
CN1360612A (zh) * | 1999-07-09 | 2002-07-24 | 伯温德药品服务公司 | 基于聚乙烯醇的涂膜和涂膜组合物 |
WO2012064805A1 (en) * | 2010-11-10 | 2012-05-18 | Novartis Ag | Salt(s) of 7-cyclopentyl-2 -(5-piperazin-1-yl-pyridin-2-ylamino)-7h-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide and processes of making thereof |
US20140018433A1 (en) * | 2012-07-13 | 2014-01-16 | Gtx, Inc. | Method of treating androgen receptor (ar) -positive breast cancers with selective androgen receptor modulator (sarms) |
EP2742940A1 (en) * | 2012-12-13 | 2014-06-18 | IP Gesellschaft für Management mbH | Salts of aza-bicyclo-di-aryl ethers for adminstration once daily, twice daily or thrice daily |
WO2014097125A1 (en) * | 2012-12-20 | 2014-06-26 | Novartis Ag | Pharmaceutical combination comprising binimetinib |
EP3283058A1 (en) * | 2015-04-16 | 2018-02-21 | Novartis AG | Ribociclib tablet |
CN109953966A (zh) * | 2017-12-26 | 2019-07-02 | 天津耀辰实业发展有限公司 | 一种含有瑞博西尼的药物组合物及其制备方法 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5428812A (en) * | 1977-08-09 | 1979-03-03 | Yoshitomi Pharmaceut Ind Ltd | Preparation of coated tablet |
GB9414045D0 (en) | 1994-07-12 | 1994-08-31 | Berwind Pharma Service | Moisture barrier film coating composition, method, and coated form |
US8685980B2 (en) | 2008-08-22 | 2014-04-01 | Novartis Ag | Pyrrolopyrimidine compounds and their uses |
CA2827027C (en) * | 2011-02-11 | 2019-06-04 | Wista Laboratories Ltd. | Phenothiazine diaminium salts and their use |
CN105209073A (zh) * | 2013-03-21 | 2015-12-30 | 诺华股份有限公司 | 包含B-Raf抑制剂和第二抑制剂的组合疗法 |
EP2810644A1 (en) * | 2013-06-06 | 2014-12-10 | Ferrer Internacional, S.A. | Oral formulation for the treatment of cardiovascular diseases |
JP7347388B2 (ja) | 2020-09-25 | 2023-09-20 | 信越化学工業株式会社 | 紫外線硬化型有機変性シリコーン組成物および硬化物 |
-
2016
- 2016-04-14 EP EP22203730.1A patent/EP4197530A1/en active Pending
- 2016-04-14 FI FIEP16718020.7T patent/FI3283058T3/fi active
- 2016-04-14 KR KR1020177029433A patent/KR20170137101A/ko not_active Application Discontinuation
- 2016-04-14 EP EP16718020.7A patent/EP3283058B1/en active Active
- 2016-04-14 US US15/564,534 patent/US10799506B2/en active Active
- 2016-04-14 SI SI201631661T patent/SI3283058T1/sl unknown
- 2016-04-14 TN TNP/2017/000422A patent/TN2017000422A1/en unknown
- 2016-04-14 CN CN202211237232.XA patent/CN115554257A/zh active Pending
- 2016-04-14 PT PT167180207T patent/PT3283058T/pt unknown
- 2016-04-14 SG SG11201708084PA patent/SG11201708084PA/en unknown
- 2016-04-14 BR BR112017021283A patent/BR112017021283A2/pt not_active Application Discontinuation
- 2016-04-14 AU AU2016248017A patent/AU2016248017A1/en not_active Abandoned
- 2016-04-14 PE PE2017002096A patent/PE20180035A1/es unknown
- 2016-04-14 ES ES16718020T patent/ES2938261T3/es active Active
- 2016-04-14 MX MX2017013350A patent/MX2017013350A/es unknown
- 2016-04-14 WO PCT/IB2016/052136 patent/WO2016166703A1/en active Application Filing
- 2016-04-14 AR ARP160101012A patent/AR104257A1/es unknown
- 2016-04-14 CA CA2982425A patent/CA2982425C/en active Active
- 2016-04-14 HU HUE16718020A patent/HUE061213T2/hu unknown
- 2016-04-14 CN CN201680022122.8A patent/CN107530292B/zh active Active
- 2016-04-14 HR HRP20230053TT patent/HRP20230053T1/hr unknown
- 2016-04-14 PL PL16718020.7T patent/PL3283058T3/pl unknown
- 2016-04-14 JP JP2017553915A patent/JP2018514523A/ja active Pending
- 2016-04-14 DK DK16718020.7T patent/DK3283058T3/da active
- 2016-04-14 EA EA201792290A patent/EA201792290A1/ru unknown
- 2016-04-15 TW TW105111921A patent/TW201642864A/zh unknown
-
2017
- 2017-10-01 IL IL254818A patent/IL254818A0/en unknown
- 2017-10-04 PH PH12017501820A patent/PH12017501820A1/en unknown
- 2017-10-13 CO CONC2017/0010510A patent/CO2017010510A2/es unknown
- 2017-10-13 CL CL2017002593A patent/CL2017002593A1/es unknown
- 2017-11-10 EC ECIEPI201775052A patent/ECSP17075052A/es unknown
-
2019
- 2019-03-20 AU AU2019201929A patent/AU2019201929B2/en active Active
-
2020
- 2020-08-26 US US17/003,771 patent/US20200390771A1/en not_active Abandoned
- 2020-10-06 AU AU2020250190A patent/AU2020250190A1/en not_active Abandoned
-
2022
- 2022-06-08 US US17/805,956 patent/US20230104792A1/en active Pending
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1157002A (zh) * | 1994-07-12 | 1997-08-13 | 伯温德药品服务公司 | 隔潮膜涂层组合物及其生产方法以及涂层制品 |
CN1360612A (zh) * | 1999-07-09 | 2002-07-24 | 伯温德药品服务公司 | 基于聚乙烯醇的涂膜和涂膜组合物 |
WO2012064805A1 (en) * | 2010-11-10 | 2012-05-18 | Novartis Ag | Salt(s) of 7-cyclopentyl-2 -(5-piperazin-1-yl-pyridin-2-ylamino)-7h-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide and processes of making thereof |
US20140018433A1 (en) * | 2012-07-13 | 2014-01-16 | Gtx, Inc. | Method of treating androgen receptor (ar) -positive breast cancers with selective androgen receptor modulator (sarms) |
EP2742940A1 (en) * | 2012-12-13 | 2014-06-18 | IP Gesellschaft für Management mbH | Salts of aza-bicyclo-di-aryl ethers for adminstration once daily, twice daily or thrice daily |
WO2014097125A1 (en) * | 2012-12-20 | 2014-06-26 | Novartis Ag | Pharmaceutical combination comprising binimetinib |
EP3283058A1 (en) * | 2015-04-16 | 2018-02-21 | Novartis AG | Ribociclib tablet |
CN109953966A (zh) * | 2017-12-26 | 2019-07-02 | 天津耀辰实业发展有限公司 | 一种含有瑞博西尼的药物组合物及其制备方法 |
Non-Patent Citations (1)
Title |
---|
匿名: ""欧巴代在片剂薄膜包衣中的应用"", 《中国医药工业杂志》 * |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107530292A (zh) | 瑞博西尼片剂 | |
JP6621933B2 (ja) | ヒト免疫不全ウイルスを処置するための治療組成物 | |
WO2013054872A1 (ja) | 7-[4-(4-ベンゾ[b]チオフェン-4-イル-ピペラジン-1-イル)ブトキシ]-1H-キノリン-2-オン又はその塩を含む錠剤 | |
US20060251723A1 (en) | Formulations of a SRC/ABL inhibitor | |
CA2847860A1 (en) | Pharmaceutical compositions of n-methyl-2-[3-((e)-2-pyridin-2-yl-vinyl)-1h-indazol-6-ylsulfanyl]-benzamide | |
JP2012522825A (ja) | 固体支持体に吸着された原薬 | |
US10034883B2 (en) | Mesoporous dosage forms for poorly soluble drugs | |
EP2068835A2 (en) | Imatinib compositions | |
WO2015145145A1 (en) | Pharmaceutical composition comprising lapatinib | |
EP3068380A1 (en) | Composite formulation comprising tadalafil and amlodipine | |
WO2013008253A2 (en) | Imatinib formulations | |
WO2016012898A1 (en) | Oral pharmaceutical composition of lurasidone | |
WO2014115082A1 (en) | Pharmaceutical formulations of imatinib | |
JP6824549B2 (ja) | 経口固形製剤およびその製造法 | |
AU2022215155B2 (en) | Ribociclib tablet | |
JP2018090510A (ja) | デュロキセチン塩酸塩を含む口腔内崩壊錠 | |
EP2320874A1 (en) | Solid pharmaceutical composition comprising exemestane | |
EA042324B1 (ru) | Таблетка, содержащая рибоциклиб | |
JP2009538905A (ja) | 感湿性薬物を含んで成る安定性製剤及びその製造方法 | |
JP6739289B2 (ja) | ゲフィチニブを有効成分とする医薬錠剤の製造方法 | |
JP6673798B2 (ja) | カペシタビンを有効成分とするフィルムコート医薬製剤 | |
TW202408531A (zh) | 包含葡萄糖酸內酯之哌柏西利製劑 | |
TW202348231A (zh) | 非晶形固體分散液及包含其之醫藥組合物 | |
CN102652748B (zh) | 稳定的艾夫他滨药物组合物及其制备方法 | |
JP2019026583A (ja) | エルロチニブを有効成分とする医薬錠剤及びその製造方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |