CN106580902A - 一种依匹哌唑口崩片及其制备方法 - Google Patents
一种依匹哌唑口崩片及其制备方法 Download PDFInfo
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- CN106580902A CN106580902A CN201710104058.4A CN201710104058A CN106580902A CN 106580902 A CN106580902 A CN 106580902A CN 201710104058 A CN201710104058 A CN 201710104058A CN 106580902 A CN106580902 A CN 106580902A
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- oral cavity
- disintegration tablet
- cavity disintegration
- sodium
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- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- ZKIAIYBUSXZPLP-UHFFFAOYSA-N brexpiprazole Chemical compound C1=C2NC(=O)C=CC2=CC=C1OCCCCN(CC1)CCN1C1=CC=CC2=C1C=CS2 ZKIAIYBUSXZPLP-UHFFFAOYSA-N 0.000 title abstract description 10
- 229960001210 brexpiprazole Drugs 0.000 title abstract description 10
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- QPUMEZIFDXYGPG-UHFFFAOYSA-N piperazine 1H-pyrrole Chemical class N1CCNCC1.N1C=CC=C1 QPUMEZIFDXYGPG-UHFFFAOYSA-N 0.000 claims description 25
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 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 15
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Classifications
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- A61K9/00—Medicinal preparations characterised by special physical form
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- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- 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
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- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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Abstract
本发明公开了一种依匹哌唑口崩片及其制备方法。所述口崩片是一种包含依匹哌唑、填充剂、崩解剂、润湿剂与粘合剂、矫味剂、润滑剂的药物组合物,所述制备方法采用湿法制粒压片法。本发明的目的是提供一种制备工艺简单、成本低廉、服用方便、起效迅速、生物利用度高的依匹哌唑口崩片,该剂型能提高患者的服药顺应性,有利于精神分裂症和重度抑郁症疾病的治疗。
Description
技术领域
本发明属于药物制剂领域,涉及一种包含依匹哌唑的口崩片及其制备方法。
背景技术
2014年9月25日FDA正式收到并开始审核公司和日本大冢制药共同研发的brexpiprazole新药申请(NDA)。2015年7月10日依匹哌唑(Brexpiprazole)经FDA批准,可用于精神分裂症和重度抑郁症的辅助治疗。
灵北共提交7项II和III期临床研究,其中3项为精神分裂,4项为重度抑郁症的辅助治疗,共有超过6000名患者参与。
精神分裂适应症的2个III期临床研究共有超过1200名患者参与。患者在接受治疗6周之后的阳性和阴性症状量表(PANSS)分数有大幅度的提升。PANSS为精神疾病病的评定工具。
在重度抑郁症的辅助治疗方面,brexpiprazole在II项临床III期试验中表现也要优胜于安慰剂。
灵北制药和大冢制药共同开发的brexpiprazole是一款实验性血清素-多巴胺活动调节剂(SDAM) ,可作用于多巴胺D2和5-HT2A受体。 在多巴胺D2类受体中,D2受体部分激动剂对中脑边缘通路可产生功能性拮抗作用,能有效的改善精神分裂症因D2过度活动引起的阳性症状;对中脑皮层通路可产生功能性激动作用,可改善D2功能低下所引起的阴性症状、认知损害。brexpiprazole是一种新型多靶点作用机制的用于精神障碍疾病的治疗药物,除主要具备多巴胺D2受体部分激动作用之外,还具备D3受体部分激动作用、5-HT1A部分受体激动作用和5-HT2A部分受体拮抗作用,是针对单胺类神经递质多靶点开发的同时具有抗精神分裂和抗抑郁作用的新药,目前正在进行Ⅲ期临床试验。
发明内容
本发明提供了一种包含依匹哌唑的口崩片及其制备方法。根据本发明制备得到的依匹哌唑口崩片具有崩解迅速,口感良好,生物利用度高,毒副作用小,服用方便的特点,而且制备工艺简单,成本低廉,适用于工业化生产。
本发明提供的依匹哌唑口崩片所包含的组分及其重量百分比如下:
依匹哌唑1-20%
填充剂20-80%
崩解剂5-20%
润湿剂与粘合剂1-10%
矫味剂2-6%
润滑剂0.5-5%
本发明中所述依匹哌唑的粒径范围为1~20μm,优选为1~10μm。
本发明中所述填充剂选自乳糖、糊精、预胶化淀粉、微晶纤维素、甘露醇、山梨醇、木糖醇、磷酸氢钙中的一种或几种,优选为甘露醇与乳糖或甘露醇与木糖醇的混合物,进一步优选为甘露醇与乳糖或木糖醇的重量比为2:1~6:1。
本发明中所述崩解剂选自干淀粉、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,优选为羧甲基淀粉钠或交联聚维酮,进一步优选为羧甲基淀粉钠或交联聚维酮的加入方式为内外加。
本发明中所述润湿剂与粘合剂选自纯化水、乙醇、淀粉浆、羧甲基纤维素钠、聚维酮、甲基纤维素、羟丙基纤维素、羟丙基甲基纤维素中的一种或几种,优选为聚维酮或羟丙基甲基纤维素的水或乙醇水溶液。
本发明中所述矫味剂选自山梨醇、甘露醇、甜菊苷、糖精钠、阿司帕坦、薄荷脑、香精中的一种或几种。
本发明中所述润滑剂选自硬脂酸镁、硬脂富马酸钠、微粉硅胶、滑石粉、氢化植物油、聚乙二醇、月桂醇硫酸镁中的一种或几种。
本发明中所述依匹哌唑口崩片制备方法包括如下步骤:
(1)将原料药微粉化处理,其余辅料分别研细过100目筛;
(2)将处方量的内加物料过筛混合均匀后,加入处方量的粘合剂的水或乙醇水溶液,制备软材;
(3)过20目筛制粒,于50℃烘箱中干燥至颗粒水分在1.5~3.5%之间,过24目筛整粒;
(4)向(3)中所得干颗粒中加入处方量的外加物料,混合均匀;
(5)测定中间体含量,确定片重后压片即得。
利用本发明的技术方案,可以制备得到不同含量规格的依匹哌唑口崩片,其口味芳香清爽,无砂砾感,崩解时间短,服用后容易吞咽且溶出度符合要求。同时本发明采用的制备工艺简便易行,具有很好的推广前景。
具体实施方式
下面结合具体实施例对本发明作进一步说明,以使本领域的技术人员可以更好的理解本发明并能予以实施,但所举实施例不作为对本发明的限定。
实施例1:
成分名称重量比例(%)依匹哌唑1%甘露醇50%乳糖32%羧甲基淀粉钠10%聚维酮3%阿司帕坦2%微粉硅胶1%硬脂酸镁1%
制备方法:
(1)将依匹哌唑微粉化处理,其余辅料分别研细过100目筛;
(2)将依匹哌唑、甘露醇、乳糖、处方量5%的羧甲基淀粉钠、阿司帕坦过筛混合均匀后,加入处方量浓度为20%的聚维酮乙醇水溶液,制备软材;
(3)过20目筛制粒,于50℃烘箱中干燥至颗粒水分在1.5~3.5%之间,过24目筛整粒;
(4)向(3)中所得干颗粒中加入微粉硅胶、硬脂酸镁、剩余量的羧甲基淀粉钠,混合均匀;
(5)测定中间体含量,确定片重后压片即得。
实施例2:
成分名称重量比例(%)依匹哌唑5%甘露醇45%乳糖35%交联羧甲基纤维素钠10%羟丙基纤维素2%阿司帕坦2%硬脂酸镁1%
制备方法:
(1)将依匹哌唑微粉化处理,其余辅料分别研细过100目筛;
(2)将依匹哌唑、甘露醇、乳糖、处方量5%的交联羧甲基纤维素钠、阿司帕坦过筛混合均匀后,加入处方量浓度为25%的羟丙基纤维素乙醇水溶液,制备软材;
(3)过20目筛制粒,于50℃烘箱中干燥至颗粒水分在1.5~3.5%之间,过24目筛整粒;
(4)向(3)中所得干颗粒中加入硬脂酸镁、剩余量的交联羧甲基纤维素钠,混合均匀;
(5)测定中间体含量,确定片重后压片即得。
实施例3:
成分名称重量比例(%)依匹哌唑6%甘露醇50%木糖醇31%交联聚维酮6%羟丙基纤维素4%阿司帕坦2%柠檬香精1%微粉硅胶1%硬脂酸镁1%
制备方法:
(1)将依匹哌唑微粉化处理,其余辅料分别研细过100目筛;
(2)将依匹哌唑、甘露醇、木糖醇、处方量3%的交联聚维酮、阿司帕坦、柠檬香精过筛混合均匀后,加入处方量浓度为20%的羟丙基纤维素乙醇水溶液,制备软材;
(3)过20目筛制粒,于50℃烘箱中干燥至颗粒水分在1.5~3.5%之间,过24目筛整粒;
(4)向(3)中所得干颗粒中加入微粉硅胶、硬脂酸镁、剩余量的交联聚维酮,混合均匀;
(5)测定中间体含量,确定片重后压片即得。
实施例4:
成分名称重量比例(%)依匹哌唑10%微晶纤维素82%羧甲基淀粉钠5%羟丙基甲基纤维素2%甜菊苷1.5%微粉硅胶1%硬脂酸镁0.5%
制备方法:
(1)将依匹哌唑微粉化处理,其余辅料分别研细过100目筛;
(2)将依匹哌唑、微晶纤维素、处方量4%的羧甲基淀粉钠、甜菊苷过筛混合均匀后,加入处方量浓度为20%的羟丙基甲基纤维素乙醇水溶液,制备软材;
(3)过20目筛制粒,于50℃烘箱中干燥至颗粒水分在1.5~3.5%之间,过24目筛整粒;
(4)向(3)中所得干颗粒中加入微粉硅胶、硬脂酸镁、剩余量的羧甲基淀粉钠,混合均匀;
(5)测定中间体含量,确定片重后压片即得。
Claims (8)
1.一种依匹哌唑的口崩片,以依匹哌唑为有效药物成分,其特征在于处方中采用和药物兼容性良好的药用辅料共同组成,包括填充剂、崩解剂、润湿剂与粘合剂、矫味剂、润滑剂等,以重量百分比计,各组分的比例如下:
依匹哌唑1-20%
填充剂20-80%
崩解剂5-20%
润湿剂与粘合剂1-10%
矫味剂2-6%
润滑剂0.5-5%。
2.根据权利要求1所述的口崩片,其特征在于依匹哌唑的粒径范围为1~20μm,优选为1~10μm。
3.根据权利要求1所述的口崩片,其特征在于所述填充剂选自乳糖、糊精、预胶化淀粉、微晶纤维素、甘露醇、山梨醇、木糖醇、磷酸氢钙中的一种或几种,优选为甘露醇与乳糖或甘露醇与木糖醇的混合物,进一步优选为甘露醇与乳糖或木糖醇的重量比为2:1~6:1。
4.根据权利要求1所述的口崩片,其特征在于所述崩解剂选自干淀粉、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,优选为羧甲基淀粉钠或交联聚维酮,进一步优选为羧甲基淀粉钠或交联聚维酮的加入方式为内外加。
5.根据权利要求1所述的口崩片,其特征在于所述润湿剂与粘合剂选自纯化水、乙醇、淀粉浆、羧甲基纤维素钠、聚维酮、甲基纤维素、羟丙基纤维素、羟丙基甲基纤维素中的一种或几种,优选为聚维酮或羟丙基甲基纤维素的水或乙醇水溶液。
6.根据权利要求1所述的口崩片,其特征在于所述矫味剂选自山梨醇、甘露醇、甜菊苷、糖精钠、阿司帕坦、薄荷脑、香精中的一种或几种。
7.根据权利要求1所述的口崩片,其特征在于所述润滑剂选自硬脂酸镁、硬脂富马酸钠、微粉硅胶、滑石粉、氢化植物油、聚乙二醇、月桂醇硫酸镁中的一种或几种。
8.根据权利要求1所述的口崩片,其特征在于所述制备方法包括如下步骤:
(1)将原料药微粉化处理,其余辅料分别研细过100目筛;
(2)将处方量的内加物料过筛混合均匀后,加入处方量的粘合剂的水或乙醇水溶液,制备软材;
(3)过20目筛制粒,于50℃烘箱中干燥至颗粒水分在1.5~3.5%之间,过24目筛整粒;
(4)向(3)中所得干颗粒中加入处方量的外加物料,混合均匀;
(5)测定中间体含量,确定片重后压片即得。
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