CN110721165A - 一种酒石酸匹莫范色林组合物及其制备方法 - Google Patents

一种酒石酸匹莫范色林组合物及其制备方法 Download PDF

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CN110721165A
CN110721165A CN201810778586.2A CN201810778586A CN110721165A CN 110721165 A CN110721165 A CN 110721165A CN 201810778586 A CN201810778586 A CN 201810778586A CN 110721165 A CN110721165 A CN 110721165A
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pimavanserin tartrate
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邢沙沙
王宇杰
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Beijing Wanquan Dezhong Medical Biological Technology Co Ltd
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Abstract

本发明属于医药领域，发明了一种处方组成简单、生物利用度高的酒石酸匹莫范色林组合物及其制备方法。

Description

一种酒石酸匹莫范色林组合物及其制备方法
技术领域
本发明属于药物制剂领域，具体涉及了酒石酸匹莫范色林药物组合物及其制备方法。
背景技术
匹莫范色林是一种选择性5羟色胺反向激动药，不仅优先选择性靶向5-HT2A受体，同时可以避免多数精神分裂药物所具有的多巴胺受体及其他受体激活导致的不良反应。体外试验中，匹莫范色林作为反向激动药和拮抗药对于5-HT2A受体有高的结合亲和力，对于5-HT2C受体有较低的结合亲和力，是一种非典型抗精神病药物，适用于伴随帕金森氏病精神病幻觉和妄想的治疗。
2016年ACADIA PHARMACEUTICALS INC研发的酒石酸匹莫范色林片（NUPLAZID）通过FDA的批准上市。国内暂未上市。
酒石酸匹莫范色林溶解度小，使得含有该有效成分的口服固体制剂通常具有 溶出度差，生物利用度不高等问题。本发明阐述了采用特定的工艺将酒石酸匹莫范色林涂覆在硅化微晶纤维素上，利用硅化微晶纤维素的理化性质、涂覆工艺提高酒石酸匹莫范色林的溶出量，增加生物利用度，显著提高经济效益。
发明内容
本发明提供了一种酒石酸匹莫范色林的组合物及其制备方法，该药物组合物包含酒石酸匹莫范色林、硅化微晶纤维素、填充剂、润滑剂，其中硅化微晶纤维素流动性较好，外观为球形、多孔，有助于提高酒石酸匹莫范色林的溶出。采用流化床或包衣机涂覆酒石酸匹莫范色林于硅化微晶纤维素上，可使酒石酸匹莫范色林均匀的涂覆在硅化微晶纤维素表面，也是提高溶出量的有效工艺。
本发明酒石酸匹莫范色林药物组合物，包含颗粒和药物可接受填充剂、润滑剂，其中该颗粒包含涂覆了酒石酸匹莫范色林的硅化微晶纤维素，所述硅化微晶纤维素的单个颗粒为球形，具有小于200微米的粒径。此硅化微晶纤维素可以是喷雾干燥的微晶纤维素和二氧化硅组合物，也可以是硅化微晶纤维素50或硅化微晶纤维素90。
酒石酸匹莫范色林药物组合物中的主药颗粒是在硅化微晶纤维素上涂覆了酒石酸匹莫范色林。
药物组合物的填充剂选自淀粉、预胶化淀粉、微晶纤维素。
药物组合物的润滑剂选自硬脂酸镁、硬脂酸、滑石粉，优选硬脂酸镁。
药物组合物所述颗粒是采用流化床工艺制粒、包衣或包衣机包衣工艺。
硅化微晶纤维素占药物组合物重量比的50%~80%。
填充剂占药物组合物重量比的5%~25%。
在此药物组合物及制备工艺中，硅化微晶纤维素的选择、组成配比、制备工艺是增加溶出量、提高生物利用度的关键点。
具体实施例
以下实施例进一步描述本发明的有益效果，实施例仅用于例证的目的，不限制本发明的范围。
实施例1
片芯处方组成：
酒石酸匹莫范色林 20.0%
硅化微晶纤维素50 74.0%
预胶化淀粉 5.0%
硬脂酸镁 1.0%
制备工艺：
将酒石酸匹莫范色林置于水中，制备成主药混悬液，备用；将硅化微晶纤维素置于流化床内，采用流化床顶喷制粒工艺将主药混悬液喷至硅化微晶纤维素上，烘干。外加预胶化淀粉、硬脂酸镁混合均匀，压片。
实施例2
片芯处方组成：
酒石酸匹莫范色林 20.0%
硅化微晶纤维素50 54.2%
预胶化淀粉 25.0%
硬脂酸镁 0.8%
制备工艺：
将酒石酸匹莫范色林置于水中，制备成主药混悬液，备用；将硅化微晶纤维素置于流化床内，采用流化床底喷包衣工艺将主药混悬液喷至硅化微晶纤维素上，烘干。外加预胶化淀粉、硬脂酸镁混合均匀，压片、包衣。
实施例3
片芯处方组成：
酒石酸匹莫范色林 20.0%
硅化微晶纤维素90 64.2%
预胶化淀粉 15.0%
硬脂酸镁 0.8%
制备工艺：
将酒石酸匹莫范色林置于水中，制备成主药混悬液，备用；将硅化微晶纤维素置于流化床内，采用流化床底喷包衣工艺将主药混悬液喷至硅化微晶纤维素上，烘干。外加预胶化淀粉、硬脂酸镁混合均匀，压片、包衣。
实施例4
片芯处方组成：
酒石酸匹莫范色林 20.0%
硅化微晶纤维素90 71.0%
预胶化淀粉 8.0%
硬脂酸镁 1.0%
制备工艺：
将酒石酸匹莫范色林置于水中，制备成主药混悬液，备用；将硅化微晶纤维素置于包衣机内，采用包衣机将主药混悬液涂覆在硅化微晶纤维素上，烘干。外加预胶化淀粉、硬脂酸镁混合均匀，压片、包衣。
对比实施例1
片芯处方组成：
酒石酸匹莫范色林 20.0%
硅化微晶纤维素90 71.0%
预胶化淀粉 8.0%
硬脂酸镁 1.0%
制备工艺：
称取处方量的酒石酸匹莫范色林与硅化微晶纤维素混合均匀，外加预胶化淀粉、硬脂酸镁混合均匀，压片、包衣。
按中国药典2015版第四部0931第二法浆法50转，在pH4.5介质中检测溶出度。溶出度检测结果：
时间 实施例1 实施例2 实施例3 实施例4 对比实施例1
15min/% 83.9 64.5 72.1 78.3 56.5
30min/% 99.6 89.5. 94.4 98.2 79.6
结论：通过溶出度检测结果可知，实施例1~4在15min、30min的溶出度远大于对比实施例1，说明本发明有利于提高溶出量，增强药物生物利用度。

Claims (8)

1.一种酒石酸匹莫范色林药物组合物，其包含颗粒和药物可接受填充剂、润滑剂，其中该颗粒包含涂覆了酒石酸匹莫范色林的微晶纤维素，所述微晶纤维素是硅化微晶纤维素，所述硅化微晶纤维素的单个颗粒为球形，具有小于200微米的粒径。
2.根据权利要求1所述的药物组合物，其中所述颗粒包含硅化微晶纤维素，在硅化微晶纤维素上涂覆酒石酸匹莫范色林。
3.根据权利要求1所述的药物组合物，其中所述填充剂选自淀粉、预胶化淀粉、微晶纤维素。
4.根据权利要求1所述的药物组合物，其中所述润滑剂选自硬脂酸镁、硬脂酸、滑石粉，优选硬脂酸镁。
5.根据权利要求1所述的药物组合物，其中所述硅化微晶纤维素选自喷雾干燥的微晶纤维素、二氧化硅组合物、硅化微晶纤维素50、硅化微晶纤维素90。
6.根据权利要求1所述的药物组合物，其中所述颗粒是采用流化床工艺制粒、包衣或包衣机包衣制备。
7.根据权利要求2所述，硅化微晶纤维素占药物组合物重量比的50%~80%。
8.根据权利要求3所述填充剂占药物组合物重量比的5%~20%。
CN201810778586.2A 2018-07-16 2018-07-16 一种酒石酸匹莫范色林组合物及其制备方法 Pending CN110721165A (zh)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008134005A1 (en) * 2007-04-24 2008-11-06 Jrs Pharma Lp Co-processing of active pharmaceutical/nutraceutical ingredients
CN101500568A (zh) * 2006-05-15 2009-08-05 阿卡蒂亚药品公司 匹莫范色林的药物制剂
CN106606494A (zh) * 2015-10-22 2017-05-03 天津市汉康医药生物技术有限公司 一种匹莫范色林药物组合物及其制备方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101500568A (zh) * 2006-05-15 2009-08-05 阿卡蒂亚药品公司 匹莫范色林的药物制剂
WO2008134005A1 (en) * 2007-04-24 2008-11-06 Jrs Pharma Lp Co-processing of active pharmaceutical/nutraceutical ingredients
CN106606494A (zh) * 2015-10-22 2017-05-03 天津市汉康医药生物技术有限公司 一种匹莫范色林药物组合物及其制备方法

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Application publication date: 20200124