CN1254240C - 水飞蓟宾葡甲胺盐口腔崩解片及其制备工艺 - Google Patents
水飞蓟宾葡甲胺盐口腔崩解片及其制备工艺 Download PDFInfo
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- CN1254240C CN1254240C CN 200410069355 CN200410069355A CN1254240C CN 1254240 C CN1254240 C CN 1254240C CN 200410069355 CN200410069355 CN 200410069355 CN 200410069355 A CN200410069355 A CN 200410069355A CN 1254240 C CN1254240 C CN 1254240C
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- Prior art keywords
- silybin
- methylglucamine
- meglumine salt
- agent
- disintegration tablet
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Abstract
本发明涉及一种水飞蓟宾葡甲胺盐口腔崩解片及其制备工艺，以水飞蓟宾葡甲胺盐为原料，填充剂、崩解剂、矫味剂、助流剂、润滑剂等为辅料，根据不同情况可使用粘合剂，也可酌情加入适量泡腾剂，其特征在于水飞蓟宾葡甲胺盐经粉末包衣制得水飞蓟宾葡甲胺盐粉末包衣颗粒，再与其它组分混匀、压片，得到崩解片。本发明的口腔崩解片脆碎度良好，崩解迅速，口感好，无砂砾感，不需要特殊的生产条件；具有生产成本低，携带、储藏、运输和服用方便等特点；特别适用于吞咽困难的患者或在无水条件下服用，改善患者的依从性，提高药物的疗效。
Description
[技术领域]
本发明涉及一种具有明显的保护和稳定肝细胞的作用，用于治疗急慢性肝炎、肝硬化、肝中毒等病症的水飞蓟宾葡甲胺盐制剂，尤其涉及一种具有速释作用的水飞蓟宾葡甲胺盐口腔崩解片制剂及其制备方法。
[背景技术]
水飞蓟宾葡甲胺盐是水飞蓟宾与葡甲胺(1-甲胺基-1-去氧山梨醇)结合而成，水飞蓟宾葡甲胺盐较水飞蓟宾易溶于水，故吸收速度及疗效的发挥均较水飞蓟宾为优。
水飞蓟宾葡甲胺盐与水飞蓟宾有着相同的适应症和临床疗效。
目前水飞蓟宾葡甲胺盐制剂的剂型主要有普通片和胶囊剂型。尚未发现有水飞蓟宾葡甲胺盐的口腔崩解片制剂或有关文献。将水飞蓟宾葡甲胺盐制成口腔崩解片，使患者携带和服用方便，有利于改善患者的依从性，进而可以确保水飞蓟宾葡甲胺盐疗效。
[发明内容]
本发明的目的在于改进现有的水飞蓟宾葡甲胺盐在口服剂型方面的的不足，向广大患者和医务工作者提供一种服用方便、吸收起效快、生物利用度高的水飞蓟宾葡甲胺盐口腔崩解片制剂。本发明涉及服用时不必饮水、在口腔中仅需几十秒即可迅速崩解或溶解、随唾液下咽即可完成服药的水飞蓟宾葡甲胺盐口腔崩解片及其制备方法。
一、处方
本发明所述及的水飞蓟宾葡甲胺盐口腔崩解片，包括原料药物水飞蓟宾葡甲胺盐，共需要以下9类原、辅材料，其中：不作包衣处理时，则不使用包衣材料，泡腾剂为酌情可选用辅料，也可不用。对于不作包衣处理时，处方组成：水飞蓟宾葡甲胺盐(5-50)％，粘合剂(0-5)％，填充剂(10-80)％，崩解剂(2-35)％，矫味剂(1-40)％，泡腾剂(0-30)％，助流剂(0.01-5)％，润滑剂(0.3-3)％。进行包衣处理时，本发明的水飞蓟宾葡甲胺盐口腔崩解片，通过水飞蓟宾葡甲胺盐粉末包衣制得水飞蓟宾葡甲胺盐粉末包衣颗粒，再与其它组分混匀、压片，得到崩解片，即所述的水飞蓟宾葡甲胺盐口腔崩解片，包含水飞蓟宾葡甲胺盐、填充剂、崩解剂、矫味剂、助流剂、润滑剂和包衣材料，任选存在粘合剂或泡腾剂，其中，以重量百分含量计算，水飞蓟宾葡甲胺盐5％～50％，填充剂10％～80％，崩解剂2％～35％，矫味剂1％～40％，助流剂0.01％～5％，润滑剂0.3％～3％，粘合剂0～5％，泡腾剂0～30％，包衣材料不超过40％，其特征在于：所述的包衣材料为丙烯酸树脂类，水飞蓟宾葡甲胺盐通过粉末包衣制得水飞蓟宾葡甲胺盐粉末包衣颗粒，再与其它组分混匀、压片制得崩解片。
上述所述的组分，其中：
粘合剂，包括但不仅限于淀粉、预胶化淀粉、糊精、麦芽糖糊精、蔗糖、阿拉伯胶、甲基纤维素、羧甲基纤维素、乙基纤维素、聚乙烯醇、聚乙二醇、聚乙烯吡咯烷酮(PVP)、海藻酸及海藻酸盐、黄原胶和羟丙基甲基纤维素(HPMC)，可单独使用，也可组合使用。
填充剂，包括但不仅限于甘露醇(粒状或粉状)、木糖醇、山梨醇、麦芽糖、微晶纤维素、PROSOLVSMCC、聚合糖(EMDEX)、葡萄糖、乳糖、蔗糖、糊精和淀粉等，可以单独使用，也可以组合应用，用量通常为(10-80)％。
崩解剂，包括但不仅限于微晶纤维素、PROSOLVSMCC、交联聚乙烯吡咯烷酮(PVPP)、羧甲基淀粉钠(CMS-Na)、低取代羟丙基甲基纤维素(L-HPC)、交联羧甲基纤维素钠(CCNa)和大豆多糖(EMCOSOY)等，可单独使用，也可组合使用。
矫味剂，包括但不仅限于甘露醇、木糖醇、甜菊甙、乳糖、果糖、蔗糖、蛋白糖、麦芽糖醇、甘草甜素、环己氨基磺酸钠、明胶、阿斯巴甜、香蕉香精、菠萝香精、香兰素、香橙香精、桔子香精、薄荷香精、人参香精、草莓香精、枸橼酸、柠檬酸等，可单独使用，也可组合使用。
丙烯酸树脂类，为国产丙烯酸树脂I、II、III或IV，或者尤特奇(Eudragit)系列，例如尤特奇E100(EudragitE100)。
助流剂，包括但不仅限于微粉硅胶、滑石粉、Cab-O-sil、Arosil、水合硅铝酸钠等，可单独使用，也可组合使用。
润滑剂，包括但不仅限于硬脂酸镁、硬脂酸钙、硬脂酸锌、单硬脂酸甘油脂、聚乙二醇、氢化植物油、硬脂富马酸钠、聚氧乙烯单硬脂酸酯、单月桂蔗糖酸酯、月桂醇硫酸钠、月桂醇硫酸镁、十二烷基硫酸镁和滑石粉等，可单独使用，也可组合使用。
泡腾剂，包括但不仅限于苹果酸、柠檬酸或枸橼酸与碳酸氢钠或碳酸钠的混合物。
二、制备方法
本发明所述及的水飞蓟宾葡甲胺盐口腔崩解片，其制备方法为直接压片法，具有制备常规片剂的生产厂家均可采用。
水飞蓟宾葡甲胺盐味微苦涩，本发明可采用二种不同方法进行矫味或掩味：
①采用矫味剂直接矫味；②预先将水飞蓟宾葡甲胺盐进行粉末包衣以掩味。
粉末包衣制备水飞蓟宾葡甲胺盐口腔崩解片的具体制备方法如下：
第一步取所选定的包衣材料，用与之相适应的溶媒溶解并稀释至适当浓度备用；
第二步再取水飞蓟宾葡甲胺盐置于沸腾床中使沸腾，然后以适当速度喷入上述溶液进行粉末包衣，得水飞蓟宾葡甲胺盐粉末包衣颗粒，干燥后过筛备用；
第三步将填充剂、崩解剂、矫味剂、助流剂、润滑剂、任选存在的粘合剂或泡腾剂混合均匀，再与经第二步所得之物料混合使均匀，备用；
第四步所得物料经中间体检测，确定片重后，送入压片机压片即得。
[有益效果]
片剂是一种传统剂型，因其质量稳定、剂量准确、服用、携带方便、机械化程度高、生产成本低而成为目前最常用的剂型之一，但因片剂加压成型，崩解较慢、生物利用度较低，且部分患者吞服较为困难，因而片剂的推广使用在一定程度上受到限制。为此口服固体速释制剂成为近年新药研发的一个热点，特别是口腔崩解片，因其服用方便、起效快、生物利用度高、口感好而成为片剂开发的重点。
口腔崩解片是指不需用水或只需少量水，无需咀嚼，片剂置于舌面，遇唾液迅速解或崩后，借吞咽动力，药物即可入胃起效的片剂。口腔崩解片的特点是吸收快、生物利用度高，肠道残留少，副作用低，避免肝脏首过效应等。
据《口腔崩解片的剂型特点和质量控制会议纪要》的要求，口腔崩解片比滴丸和普通片的崩解速度有本质的飞跃，口腔崩解片的崩解一般在30秒以内，最多不超过1分钟。
[具体实施例]
为了更好的说明本发明所述水飞蓟宾葡甲胺盐口腔崩解片的制备方法，结合直接矫味法和粉末包衣掩味法分别举一个实施例如下：
实施例一直接矫味法
一.处方
1.原料——水飞蓟宾葡甲胺盐100.0g；
2.粘合剂——聚乙烯吡咯烷酮K-301.0g；
3.填充剂——甘露醇154.0g；
4.矫味剂——阿斯巴甜3.0g；
桔子香精6.0g；
5.崩解剂——交联聚乙烯吡咯烷酮14.0g；
交联羧甲基纤维素钠16.0g；
6.助流剂——微粉硅胶3.0g；
7.润滑剂——硬脂富马酸钠3.0g。
总重300g，共制成2000片。
二.制备方法
1)取水飞蓟宾葡甲胺盐原料粉碎，用聚乙烯吡咯烷酮K-30制粒，水或乙醇为润湿剂，过26目筛，烘干，备用；
2)将交联聚乙烯吡咯烷酮、交联羧甲基纤维素钠、微粉硅胶、硬脂富马酸钠、桔子香精和阿斯巴甜，分别过40目筛，混合均匀，再加入已制粒的水飞蓟宾葡甲胺盐颗粒，混合均匀，备用；
3)再加入甘露醇混合均匀；
4)中间体含量检测，确定片重后，送入压片机压片即得。
实施例二粉末包衣掩味法
一.处方
1.原料——水飞蓟宾葡甲胺盐100.0g；
2.包衣材料——尤特奇E100(EudragitE100)20.0g；
3.填充剂——甘露醇132.0g；
4.矫味剂——阿斯巴甜3.0g；
桔子香精6.0g；
5.崩解剂——交联聚乙烯吡咯烷酮14.0g；
交联羧甲基纤维素钠16.0g；
6.助流剂——微粉硅胶6.0g；
7.润滑剂——硬脂富马酸钠3.0g。
总重300g，共制成2000片。
二.制备方法
1)取尤特奇E100(EudragitE100)用95％以上的药用工业乙醇溶解并稀释至一定浓度备用；
2)取水飞蓟宾葡甲胺盐置于沸腾床中沸腾，按一定速度喷入上述溶液进行粉末包衣，制得水飞蓟宾葡甲胺盐粉末包衣颗粒，干燥后备用；
3)将甘露醇、微粉硅胶、PVPP、L-HPC、阿斯巴甜、硬脂富马酸钠和桔子香精混合均匀，再和过筛后的包衣颗粒混匀备用；
4)中间体含量检测，确定片重后，送入压片机压片即得。
Claims (2)
1.一种水飞蓟宾葡甲胺盐口腔崩解片，其特征在于其重量组成为水飞蓟宾葡甲胺盐5～50％、包衣材料聚丙烯酸树脂6.67～40％、崩解剂交联聚乙烯吡咯烷酮2～35％、填充剂10-80％、矫味剂1～40％、助流剂0.01～5％、润滑剂0.3～3％组成，其中填充剂选自甘露醇、微晶纤维素、糊精、乳糖、淀粉、麦芽糖糊精和预胶化淀粉中的一种或多种，矫味剂选自甘露醇、乳糖、甜菊甙、明胶、阿斯巴甜、甜蜜素、甘草甜素、香橙香精、桔子香精、薄荷香精、人参香精、草莓香精、枸橼酸、柠檬酸中的一种或多种，助流剂选自微粉硅胶、滑石粉、Cab-O-sil、Arosil、水合硅铝酸钠中的一种或多种，润滑剂选自硬脂酸镁、单硬脂酸甘油脂、十二烷基硫酸镁、滑石粉中的一种或多种；其中将水飞蓟宾葡甲胺盐用包衣材料进行粉末包衣后，所得颗粒与其它辅料一起压制成崩解片。
2.如权利要求1所述的水飞蓟宾葡甲胺盐口腔崩解片的制备方法，其特征在于由以下步骤组成：
第一步水飞蓟宾葡甲胺盐的预处理；取所选定的包衣材料，用与之相适应的溶媒溶解并稀释至适当浓度备用，再取水飞蓟宾葡甲胺盐置于流化床中使沸腾，然后以适当速度喷入上述溶液进行粉末包衣，得水飞蓟宾葡甲胺盐粉末包衣颗粒，干燥后过筛备用；
第二步将矫味剂与水飞蓟宾葡甲胺盐颗粒或经第一步掩味处理后的原料颗粒按量称取，并混合均匀备用；
第三步将填充剂、崩解剂、助流剂按量称取并混合均匀，再与经第二步所得之物料混合使均匀，加入润滑剂混匀，备用；
第四步所得物料经中间体检测，确定片重后，送入压片机压片即得。
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| CN103768048B (zh) * | 2012-10-21 | 2015-11-25 | 江苏中兴药业有限公司 | 水飞蓟宾葡甲胺片及其降脂作用 |
| CN111297814A (zh) * | 2019-12-18 | 2020-06-19 | 湖南千金协力药业有限公司 | 一种降低雷公藤多苷片肝毒性的复方制剂及其制备方法 |
| CN112587488B (zh) * | 2020-12-16 | 2022-12-06 | 福建瑞泰来医药科技有限公司 | 一种水飞蓟宾组合物及其制备方法 |
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