CN107961221A - 一种含有盐酸普拉格雷的药物组合物及其制备方法 - Google Patents
一种含有盐酸普拉格雷的药物组合物及其制备方法 Download PDFInfo
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- CN107961221A CN107961221A CN201610912792.9A CN201610912792A CN107961221A CN 107961221 A CN107961221 A CN 107961221A CN 201610912792 A CN201610912792 A CN 201610912792A CN 107961221 A CN107961221 A CN 107961221A
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- prasugrel hydrochloride
- pharmaceutical composition
- adipic acid
- ethyl alcohol
- absolute ethyl
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- JALHGCPDPSNJNY-UHFFFAOYSA-N [5-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-6,7-dihydro-4h-thieno[3,2-c]pyridin-2-yl] acetate;hydron;chloride Chemical compound Cl.C1CC=2SC(OC(=O)C)=CC=2CN1C(C=1C(=CC=CC=1)F)C(=O)C1CC1 JALHGCPDPSNJNY-UHFFFAOYSA-N 0.000 title claims abstract description 88
- 229960004947 prasugrel hydrochloride Drugs 0.000 title claims abstract description 88
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims description 26
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims abstract description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 39
- 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 claims abstract description 28
- 239000000787 lecithin Substances 0.000 claims abstract description 28
- 235000010445 lecithin Nutrition 0.000 claims abstract description 28
- 229940067606 lecithin Drugs 0.000 claims abstract description 28
- 239000001361 adipic acid Substances 0.000 claims abstract description 25
- 235000011037 adipic acid Nutrition 0.000 claims abstract description 25
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 24
- GCNNVAWVYJUFCO-UHFFFAOYSA-N ethanol;hexanedioic acid Chemical group CCO.OC(=O)CCCCC(O)=O GCNNVAWVYJUFCO-UHFFFAOYSA-N 0.000 claims description 22
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- 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 8
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
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- ZPOODPZCZLCUAN-UHFFFAOYSA-N 3,4-dihydro-1h-pyridin-2-one Chemical compound O=C1CCC=CN1 ZPOODPZCZLCUAN-UHFFFAOYSA-N 0.000 description 2
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
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- 239000002253 acid Substances 0.000 description 2
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 2
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- 239000002207 metabolite Substances 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical class [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 2
- 229960004197 prasugrel Drugs 0.000 description 2
- DTGLZDAWLRGWQN-UHFFFAOYSA-N prasugrel Chemical compound C1CC=2SC(OC(=O)C)=CC=2CN1C(C=1C(=CC=CC=1)F)C(=O)C1CC1 DTGLZDAWLRGWQN-UHFFFAOYSA-N 0.000 description 2
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- LMIOYAVXLAOXJI-UHFFFAOYSA-N 3-ethyl-3-[[4-[(3-ethyloxetan-3-yl)methoxymethyl]phenyl]methoxymethyl]oxetane Chemical compound C=1C=C(COCC2(CC)COC2)C=CC=1COCC1(CC)COC1 LMIOYAVXLAOXJI-UHFFFAOYSA-N 0.000 description 1
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- 229930195725 Mannitol Natural products 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
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- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
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- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- CBMPTFJVXNIWHP-UHFFFAOYSA-L disodium;hydrogen phosphate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].OP([O-])([O-])=O.OC(=O)CC(O)(C(O)=O)CC(O)=O CBMPTFJVXNIWHP-UHFFFAOYSA-L 0.000 description 1
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- RDRCCJPEJDWSRJ-UHFFFAOYSA-N pyridine;1h-pyrrole Chemical compound C=1C=CNC=1.C1=CC=NC=C1 RDRCCJPEJDWSRJ-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
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Classifications
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明属于医药技术领域,具体涉及一种含有盐酸普拉格雷的药物组合物,所述的药物组合物含有盐酸普拉格雷、卵磷脂、崩解剂和润滑剂,还含有己二酸无水乙醇。本发明的产品稳定性好,溶出完全,具有更加优秀的产品质量;本发明的产品生产操作简单易行,适合于工业生产。
Description
技术领域
本发明属于医药技术领域,具体涉及一种含有盐酸普拉格雷的药物组合物及其片剂的制备方法。
背景技术
盐酸普拉格雷是新的口服有效的噻吩并吡啶类药物,与氯吡格雷一样,盐酸普拉格雷也是一个无活性的前体药物,需经细胞色素P450酶系代谢转化至活性代谢物后才能不可逆地抑制血小板上的P2Y12二磷酸腺苷受体。盐酸普拉格雷的疗效优于氯吡格雷,这可以从其药动学性质改善得到解释,盐酸普拉格雷具有更高的前体药物至活性代谢物转化率以及更高的生物利用度,所以起效更快并能降低个体间的疗效差异,更大程度地降低主要缺血性心血管事件的发生率。它具有良好的血小板凝集抑制作用的氢化吡啶的衍生物,良好的口服吸收性,代谢活性和血小板凝聚抑制作用,同时毒性低,因此特别用来预防或治疗优选血栓或栓塞引起的疾病。
盐酸普拉格雷的结构式如式(I)所示,其为白色至类白色固体,溶解于pH=2的溶液中,微溶于pH=3~4的溶液中,几乎不溶于pH=6.0~7.5的溶液。盐酸普拉格雷对湿、热敏感,特别是在有氧的条件下,盐酸普拉格雷会发生自由基转化而降解,影响药品质量。目前,已有许多针对提高盐酸普拉格雷制剂溶出度和稳定度的研究。在给药时选择盐酸盐的形式,并且通过口服形式比如片剂或者胶囊剂进行给药,专利1到专利4公开了多种含有各种辅料的盐酸普拉格雷制剂,主要为了解决含量均匀性、药物溶解度、提高药物制剂稳定性等技术问题。
专利1:CN200780044795公开了盐酸普拉格雷的制剂处方中包含乳糖或甘露醇,且其粒径D90在80到300um之间,用以提高含量均匀性;
专利2:CN200780044970公开了盐酸普拉格雷的制剂处方中包含2.5%-40.0%低取代的羟丙基纤维素,用以提高药物溶解度;
专利3:CN200780044960公开了含有盐酸普拉格雷及其盐的包衣层的膜层,所述膜层选自含有聚乙烯醇、PVA,CMC-NA羧甲基纤维素钠和支链淀粉的包衣材料,用以以提高药物制剂的稳定性;
专利4:CN200780044906公开了盐酸普拉格雷及其盐的药物制剂中含有一种诸如羟丙基纤维素,羟丙甲基纤维素(HPMC)或者聚乙烯吡咯烷酮等水溶性的聚合物,用以提高药物制剂的稳定性。
发明内容
在研究中发现盐酸普拉格雷在碱性条件下容易转变为普拉格雷,而游离碱会降低生物利用度,而且盐酸普拉格雷在制备过程中遇水或有机试剂,或者在水分较高的情况下容易降解,因此我们选用了干法制粒的工艺避免接触有机溶剂或水,尽可能减少了组合物中水分的含量,同时在储存时保持较好的稳定性。
本发明的目的是提供一种新的含有盐酸普拉格雷的药物组合物,该含有盐酸普拉格雷的药物组合物的稳定性好,溶出好。
本发明的另一个目的在于提供一种含有盐酸普拉格雷的药物组合物的制备方法,该方法适合工业生产。
具体而言,本发明提供了:
一种含有盐酸普拉格雷的药物组合物,含有:盐酸普拉格雷、卵磷脂、崩解剂和润滑剂,还含有己二酸无水乙醇。
所述的含有盐酸普拉格雷的药物组合物为片剂。
所述的含有盐酸普拉格雷的药物组合物,各组分的重量比为:
所述的崩解剂选自干淀粉、羧甲基淀粉钠、低取代羟丙基纤维素、聚维酮K30、交联羧甲基纤维素钠中的一种或几种。
所述的润滑剂选自微粉硅胶、滑石粉、硬脂酸镁中的一种或几种。
所述的己二酸无水乙醇的质量分数为1%~8%,优选5%。
所述的含有盐酸普拉格雷的药物组合物制备成片剂,其制备方法包括以下步骤:
(1)取己二酸加入无水乙醇中制成质量分数为1%~8%的己二酸无水乙醇溶液;
(2)将盐酸普拉格雷原料药、卵磷脂、润滑剂、崩解剂分别过60目筛;
(3)将盐酸普拉格雷原料药、卵磷脂、崩解剂进行混合,边混合边喷洒己二酸无水乙醇溶液,再加入润滑剂混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
本发明与现有技术相比具有以下优点和积极效果:
1、本发明的产品稳定性好,溶出完全。
2、本发明的产品生产操作简单易行,适合于工业生产。
具体实施方式
以下通过具体实施方式的描述对本发明作进一步说明,但这并非是对本发明的限制,本领域技术人员根据本发明的基本思想,可以做出各种修改或改进,但是只要不脱离本发明的基本思想,均在本发明的范围之内。
试验方法
【含量测定】照高效液相色谱法(中国药典2015年版四部通则0512)测定。
色谱条件与系统适用性试验用十八烷基硅烷键合硅胶为填充剂;以25mmol/L磷酸二氢钾溶液(用磷酸调节pH值至4.0)-乙腈(45:55)为流动相;检测波长为220nm;柱温45℃,流速为每分钟1.2ml。
测定法取本品20片,精密称定,研细,精密称取细粉适量(约相当于盐酸普拉格雷10mg),置100ml量瓶中,加乙腈-水(70:30)适量,振摇使溶解,用乙腈-水(70:30)稀释至刻度,摇匀,滤过,精密量取10μl注入液相色谱仪,记录色谱图;另取盐酸普拉格雷对照品,同法测定,按外标法以峰面积计算,即得。
【有关物质】临用新制。取本品细粉适量,加乙腈-水(70:30)溶解并稀释制成每1ml中约含盐酸普拉格雷2.5mg的溶液,滤过,作为供试品溶液;精密量取适量,用乙腈-水(70:30)定量稀释制成每1ml中含盐酸普拉格雷约2.5μg的溶液,作为对照溶液。照高效液相色谱法(中国药典2015年版四部通则0512)测定,用十八烷基硅烷键合硅胶为填充剂(Synergi 4μ MAX-RP 80A,4.6mm×150mm,4μm);以25mmol/L磷酸二氢钾溶液(用磷酸调节pH值至4.0)-乙腈(90:10)为流动相A,以乙腈-水(90:10)为流动相B,按下表进行线性梯度洗脱;检测波长为210nm;柱温45℃;流速为每分钟1.5ml。精密量取对照溶液和供试品溶液各20μl,分别注入液相色谱仪,记录色谱图。
杂质二酮:1-环丙基-2-(2-氟苯基)乙烷-1,2-二酮
杂质CATP:5-(5-氯-1-(2-氟苯基)-2-氧代戊基)-4,5,6,7-四氢噻吩并[3,2-c]吡啶-2-基乙酸乙酯
杂质HYTP:5-(2-环丙基-1-(2-氟苯基)-2-氧代乙基)-7a-羟基5,6,7四氢噻吩并[3,2-c]吡啶-2(4H)-酮
杂质OXTP:5-(2-环丙基-1-(2-氟苯基)-2-氧代乙基)-5,6,7,7a四氢噻吩并[3,2-c]吡啶-2(4H)-酮
【溶出度】取本品,照溶出度与释放度测定法(中国药典2015年版四部通则0931第二法),以枸橼酸-磷酸氢二钠缓冲液(pH4.0,取枸橼酸4.84g,磷酸氢二钠9.31g,加水使溶解成1000ml)900ml为溶出介质,转速为每分钟50转,依法操作,经30分钟时,取溶液10ml,滤过,取续滤液作为供试品溶液;另取盐酸普拉格雷对照品约10mg,精密称定,置100ml量瓶中,加乙腈10ml使溶解,用溶出介质稀释至刻度,摇匀,精密量取1ml置10ml量瓶中,用溶出介质稀释至刻度,摇匀,作为对照品溶液。照高效液相色谱法(中国药典2015年版四部通则0512)测定。用十八烷基硅烷键合硅胶为填充剂;以0.01mol/L磷酸二氢钾(pH2.8)-乙腈(45:55)为流动相;检测波长为220nm;柱温30℃,流速为每分钟1.5ml。精密量取供试品溶液与对照品溶液各50μ1,分别注入液相色谱仪。按外标法以峰面积计算每片的溶出量。
试验例1:处方筛选试验
分别取盐酸普拉格雷1.0g(含量99.9%,总杂0.29%),按下述处方(见表1)制得含有盐酸普拉格雷片,检测溶出度及有关物质,结果见表2:
表1盐酸普拉格雷处方(单位:g)
处方1制备方法
(1)将盐酸普拉格雷原料药、微晶纤维素、硬脂酸镁、羧甲基淀粉钠分别过60目筛。
(2)将盐酸普拉格雷原料药、微晶纤维素、羧甲基淀粉钠进行混合,边混合边喷洒无水乙醇溶液,再加入硬脂酸镁混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
处方2-4制备方法
(1)取己二酸加入无水乙醇中制成己二酸无水乙醇溶液;
(2)将盐酸普拉格雷原料药、微晶纤维素、硬脂酸镁、羧甲基淀粉钠分别过60目筛;
(3)将盐酸普拉格雷原料药、微晶纤维素、羧甲基淀粉钠进行混合,边混合边喷洒己二酸无水乙醇溶液,再加入硬脂酸镁混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
表2试验结果
结论:采用本发明处方制备的盐酸普拉格雷片剂中杂质的量显著低于无己二酸无水乙醇添加的处方。
试验例2:处方筛选试验
分别取盐酸普拉格雷1.0g(含量99.9%,总杂0.29%),按下述处方(见表3)制得含有盐酸普拉格雷片,检测溶出度及有关物质,结果见表4:
表3填充剂处方(单位:g)
制备方法
(1)取己二酸加入无水乙醇中制成质量分数为5%的己二酸无水乙醇溶液;
(2)将盐酸普拉格雷原料药、填充剂、硬脂酸镁、羧甲基淀粉钠分别过60目筛;
(3)将盐酸普拉格雷原料药、填充剂、羧甲基淀粉钠进行混合,边混合边喷洒5%己二酸无水乙醇溶液,再加入硬脂酸镁混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
表4试验结果
结论:采用卵磷脂作为填充剂制备的盐酸普拉格雷片剂的有关物质显著低于采用其他填充剂制备盐酸普拉格雷片剂。
试验例3:加速试验
取实施例5、6产品制得的产品进行加速试验,结果见表5。
表5盐酸普拉格雷片加速试验数据
包装:市售包装,考察条件:温度40℃,湿度75%
结论:由上表可知道,按本发明方法制备的产品,在高温及光照下的稳定性较好。
制备实施例
实施例1
处方
制备方法
(1)取己二酸加入无水乙醇中制成质量分数为5%的己二酸无水乙醇溶液;
(2)将盐酸普拉格雷原料药、卵磷脂、微粉硅胶、羧甲基淀粉钠分别过60目筛。
(3)将盐酸普拉格雷原料药、卵磷脂、羧甲基淀粉钠进行混合,边混合边喷洒5%的己二酸无水乙醇溶液,再加入微粉硅胶混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
实施例2
处方
制备方法
(1)取己二酸加入无水乙醇中制成质量分数为5%的己二酸无水乙醇溶液;
(2)将盐酸普拉格雷原料药、卵磷脂、滑石粉、干淀粉分别过60目筛。
(3)将盐酸普拉格雷原料药、卵磷脂、干淀粉进行混合,边混合边喷洒5%的己二酸无水乙醇溶液,再加入滑石粉混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
实施例3
处方
制备方法
(1)取己二酸加入无水乙醇中制成质量分数为5%己二酸无水乙醇溶液;
(2)将盐酸普拉格雷原料药、卵磷脂、微粉硅胶、羧甲基淀粉钠分别过60目筛。
(3)将盐酸普拉格雷原料药、卵磷脂、羧甲基淀粉钠进行混合,边混合边喷洒5%己二酸无水乙醇溶液,再加入微粉硅胶混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
实施例4
处方
制备方法
(1)取己二酸加入无水乙醇中制成质量分数为5%己二酸无水乙醇溶液;
(2)将盐酸普拉格雷原料药、卵磷脂、硬脂酸镁、交联聚乙烯吡咯烷酮分别过60目筛。
(3)将盐酸普拉格雷原料药、卵磷脂、交联聚乙烯吡咯烷酮进行混合,边混合边喷洒5%己二酸无水乙醇溶液,再加入硬脂酸镁混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
实施例5
处方
制备方法
(1)取己二酸加入无水乙醇中制成质量分数为5%己二酸无水乙醇溶液;
(2)将盐酸普拉格雷原料药、卵磷脂、微粉硅胶、交联羧甲基纤维素钠分别过60目筛。
(3)将盐酸普拉格雷原料药、卵磷脂、交联羧甲基纤维素钠进行混合,边混合边喷洒5%己二酸无水乙醇溶液,再加入微粉硅胶混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
实施例6
处方
制备方法
(1)取己二酸加入无水乙醇中制成质量分数为5%己二酸无水乙醇溶液;
(2)将盐酸普拉格雷原料药、卵磷脂、滑石粉、硬脂酸镁、干淀粉分别过60目筛。
(3)将盐酸普拉格雷原料药、卵磷脂、干淀粉进行混合,边混合边喷洒5%己二酸无水乙醇溶液,再加入滑石粉、硬脂酸镁混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
实施例7
处方
制备方法
(1)取己二酸加入无水乙醇中制成质量分数为5%己二酸无水乙醇溶液;
(2)将盐酸普拉格雷原料药、卵磷脂、微粉硅胶、低取代羟丙基纤维素分别过60目筛。
(3)将盐酸普拉格雷原料药、卵磷脂、低取代羟丙基纤维素进行混合,边混合边喷洒5%己二酸无水乙醇溶液,再加入微粉硅胶混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
实施例8
处方
制备方法
(1)取己二酸加入无水乙醇中制成质量分数为5%己二酸无水乙醇溶液;
(2)将盐酸普拉格雷原料药、卵磷脂、微粉硅胶、低取代羟丙基纤维素分别过60目筛。
(3)将盐酸普拉格雷原料药、卵磷脂、低取代羟丙基纤维素进行混合,边混合边喷洒5%己二酸无水乙醇溶液,再加入微粉硅胶混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
实施例9
处方
制备方法
(1)取己二酸加入无水乙醇中制成质量分数为5%己二酸无水乙醇溶液;
(2)将盐酸普拉格雷原料药、卵磷脂、滑石粉、交联羧甲基纤维素钠分别过60目筛。
(3)将盐酸普拉格雷原料药、卵磷脂、交联羧甲基纤维素钠进行混合,边混合边喷洒5%己二酸无水乙醇溶液,再加入滑石粉混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
实施例10
处方
制备方法
(1)取己二酸加入无水乙醇中制成质量分数为5%己二酸无水乙醇溶液;
(2)将盐酸普拉格雷原料药、卵磷脂、微粉硅胶、低取代羟丙基纤维素分别过60目筛。
(3)将盐酸普拉格雷原料药、卵磷脂、低取代羟丙基纤维素进行混合,边混合边喷洒5%己二酸无水乙醇溶液,再加入微粉硅胶混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
Claims (8)
1.一种含有盐酸普拉格雷的药物组合物,包括:盐酸普拉格雷、卵磷脂、崩解剂和润滑剂,其特征在于,还含有己二酸无水乙醇。
2.根据权利要求1所述的含有盐酸普拉格雷的药物组合物,其特征在于药物组合物制备成片剂。
3.根据权利要求1所述的含有盐酸普拉格雷的药物组合物,其特征在于各组分的重量比为:
4.根据权利要求1所述的含有盐酸普拉格雷的药物组合物,其特征在于,所述的润滑剂选自微粉硅胶、滑石粉、硬脂酸镁中的一种或几种。
5.根据权利要求1所述的含有盐酸普拉格雷的药物组合物,其特征在于,所述的崩解剂选自干淀粉、羧甲基淀粉钠、低取代羟丙基纤维素、交联聚维酮、交联羧甲基纤维素钠中的一种或几种。
6.根据权利要求1所述的含有盐酸普拉格雷的药物组合物,其特征在于,所述的己二酸无水乙醇的质量分数为1%~8%。
7.根据权利要求6所述的含有盐酸普拉格雷的药物组合物,其特征在于,所述的己二酸无水乙醇的质量分数为优选5%。
8.根据权利要求1所述的含有盐酸普拉格雷的药物组合物的制备方法,其制备方法包括以下步骤:
(1)取己二酸加入无水乙醇中制成质量分数为己二酸无水乙醇溶液;
(2)将盐酸普拉格雷原料药、卵磷脂、润滑剂、崩解剂分别过60目筛;
(3)将盐酸普拉格雷原料药、卵磷脂、崩解剂进行混合,边混合边喷洒己二酸无水乙醇溶液,再加入润滑剂混合制粒,在40℃干燥后压片,得盐酸普拉格雷片剂。
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CN102885774A (zh) * | 2011-07-18 | 2013-01-23 | 李勤耕 | 普拉格雷组合物及其制备方法 |
CN102949357A (zh) * | 2011-08-17 | 2013-03-06 | 山东新时代药业有限公司 | 一种氢溴酸普拉格雷的片剂 |
WO2013091595A1 (en) * | 2011-12-22 | 2013-06-27 | Zentiva K.S. | Pharmaceutical formulation of prasugrel hydrobromide |
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CN102885774A (zh) * | 2011-07-18 | 2013-01-23 | 李勤耕 | 普拉格雷组合物及其制备方法 |
CN102949357A (zh) * | 2011-08-17 | 2013-03-06 | 山东新时代药业有限公司 | 一种氢溴酸普拉格雷的片剂 |
WO2013091595A1 (en) * | 2011-12-22 | 2013-06-27 | Zentiva K.S. | Pharmaceutical formulation of prasugrel hydrobromide |
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