CN107184560B - 二甲双胍胃滞留片及制备方法 - Google Patents

二甲双胍胃滞留片及制备方法 Download PDF

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CN107184560B
CN107184560B CN201710410488.9A CN201710410488A CN107184560B CN 107184560 B CN107184560 B CN 107184560B CN 201710410488 A CN201710410488 A CN 201710410488A CN 107184560 B CN107184560 B CN 107184560B
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CN107184560A (zh
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张勇
宋伟国
方浩
崔鑫
李新建
李法辉
杨磊
何英俊
宋成刚
杨大伟
董良军
高东圣
杨春程
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SHOUGUANG FUKANG PHARMACEUTICAL CO Ltd
Qingdao Huanghai Pharmaceutical Co Ltd
Shandong University
Weifang University of Science and Technology
Weifang Medical University
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SHOUGUANG FUKANG PHARMACEUTICAL CO Ltd
Qingdao Huanghai Pharmaceutical Co Ltd
Shandong University
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Abstract

一种含有500毫克二甲双胍的漂浮膨胀协同型二甲双胍胃滞留片，其包含500毫克二甲双胍以及羟丙纤维素、聚氧乙烯、羧甲基淀粉钠以及着色剂和硬脂酸镁，其针对不同的胃部滞留时间对配方作了进一步限定，该产品释药规律稳定，能满足不同患者群体的医用需求，体内释药平稳,缓释效果良好,基本达到了漂浮制剂延长胃内滞留时间,提高生物利用度的剂型。

Description

二甲双胍胃滞留片及制备方法
技术领域
本发明属于医药领域，尤其涉及一种二甲双胍胃滞留片及制备方法。
背景技术
二甲双胍自1957年问世，应用于临床已有50多年的历史，是当前全球应用最广泛的口服隆糖药之一。国内外主要糖尿病指南均建议：无论患者超重与否，除非有肾损害的证据或风险，均应从一开始就使用二甲双胍治疗，且联合冶疗方案中都应包括二甲双胍，充分体现了二甲双胍在糖尿病治疗中的“基石”地位。然而在临床工作中，经常会遇到患者有腹泻、恶心、呕吐、胃胀、乏力、消化不良等胃肠道不适的情况，此时二甲双胍胃膨胀滞留缓释片(泰白)可以作为此类患者的新选择。传统的二甲双胍片为单一配方，不能满足不同胃部滞留时间的要求。
发明内容
本发明提供一种二甲双胍胃滞留片，在针对不同的胃部滞留时间时提供不同的配比，以满足不同患者需求。
一种含有500毫克二甲双胍的漂浮膨胀协同型二甲双胍胃滞留片，其包含500毫克二甲双胍以及羟丙纤维素、聚氧乙烯、羧甲基纤维素钠以及着色剂和硬脂酸镁，其中，胃滞留时间大于3小时小于5小时时，该滞留片配方为：羟丙纤维素60mg、聚氧乙烯30mg、羧甲基纤维素钠210mg,胃滞留时间大于5小时小于6小时，该滞留片配方为：羟丙纤维素90mg、聚氧乙烯15mg、羧甲基纤维素钠180mg、着色剂和硬脂酸镁15mg，胃滞留时间大于6小时小于8小时，该滞留片配方为：羟丙纤维素120mg、羧甲基纤维素钠150mg、着色剂和硬脂酸镁30mg，胃滞留时间大于8小时小于9小时，该滞留片配方为：羟丙纤维素210mg、羧甲基纤维素钠60mg、着色剂和硬脂酸镁30mg，胃滞留时间大于9小时小于10小时，该滞留片配方为：羟丙纤维素180mg、聚氧乙烯15mg、羧甲基纤维素钠90mg、着色剂和硬脂酸镁15mg，胃滞留时间大于10小时时，该滞留片配方为：羟丙纤维素150mg、聚氧乙烯30mg、羧甲基纤维素钠120mg。
一种含有500毫克二甲双胍的生物黏附膨胀协同型二甲双胍胃滞留片，其包含500毫克二甲双胍以及壳聚糖、共聚维酮、聚氧乙烯以及着色剂和硬脂酸镁，其中，胃滞留时间大于3小时小于5小时时，该滞留片配方为：壳聚糖15mg、聚氧乙烯255mg、共聚维酮15mg、着色剂和硬脂酸镁15mg,胃滞留时间大于5小时小于6小时，该滞留片配方为：壳聚糖30mg、聚氧乙烯240mg、共聚维酮15mg、着色剂和硬脂酸镁15mg，胃滞留时间大于6小时小于8小时，该滞留片配方为：壳聚糖30mg、聚氧乙烯225mg、共聚维酮30mg、着色剂和硬脂酸镁15mg，胃滞留时间大于8小时小于9小时，该滞留片配方为：壳聚糖45mg、聚氧乙烯195mg、共聚维酮45mg、着色剂和硬脂酸镁15mg，胃滞留时间大于9小时小于10小时，该滞留片配方为：壳聚糖15mg、聚氧乙烯225mg、共聚维酮45mg、着色剂和硬脂酸镁15mg，胃滞留时间大于10小时时，该滞留片配方为：壳聚糖45mg、聚氧乙烯225mg、共聚维酮15mg、着色剂和硬脂酸镁15mg。
本发明还提供一种制备上述片剂的方法，所有赋形剂(羟丙甲纤维素HPMC，羟丙纤维素HPC，羧甲基纤维素钠NaCMC，聚氧乙烯PEO 8000K,壳聚糖，共聚维酮，微晶纤维素)及硬脂酸镁和着色剂，在压片前分别通过60号筛，然后将混合物用德国Fette压片机压缩成型，具体压片方法是使用1吨平面冲头对混合物压6秒成形，聚合物配方根据质量源于设计(QbD)的原则进行试验设计。
本发明针对不同的胃部滞留时间时提供不同的配比，丰富了产品类型，以满足不同患者服用需求，具有良好的市场应用价值。
具体实施方式
1.漂浮膨胀协同型配方包含羟丙纤维素Klucel(Hydroxypropylcellulose),聚氧乙烯polyethylene oxide(PEO 8000K),羧甲基纤维素钠NaCMC 450cps,其它成分(包括着色剂和硬脂酸镁):
含有500毫克二甲双胍的配方：
Figure GDA0002536482650000021
2.生物黏附膨胀协同型配方包含壳聚糖,共聚维酮，聚氧乙烯polyethyleneoxide(PEO 8000K),其它成分(包括着色剂和硬脂酸镁):
含有500毫克二甲双胍的配方：
Figure GDA0002536482650000022
Figure GDA0002536482650000031
一种片剂的制备方法：所有赋形剂(羟丙甲纤维素HPMC，羟丙纤维素HPC，羧甲基纤维素钠NaCMC，聚氧乙烯PEO 8000K,壳聚糖，共聚维酮，微晶纤维素)及硬脂酸镁和碳酸盐，在压片前分别通过60号筛，然后将混合物用德国Fette压片机压缩成型。具体压片方法是使用1吨平面冲头对混合物压6秒成形，聚合物配方根据质量源于设计(QbD)的原则进行试验设计(Design of Experiment,DOE)。
该胃滞留片的漂浮给药***为一类重要的口服缓控释给药***,该类制剂可延长药物在胃内的滞留时间,通过平稳释放来改善药物吸收,提高药物生物利用度.盐酸二甲双胍是一种双胍类口服降糖药,主要用于治疗2型糖尿病(非胰岛素依赖型糖尿病),普通制剂在胃内停留时间短,吸收虽然迅速但不完全,口服生物利用度仅为50％一60％；此外,20％以上患者服用盐酸二甲双胍后有腹部不适、恶心等不良反应[1].将盐酸二甲双胍制成胃滞留片,既可避免胃局部药物浓度过高引起的胃肠道刺激,同时可延长药物在胃肠道的吸收时间,大大提高生物利用度该胃滞留缓释片,对其质量控制和漂浮膨胀性能以及体外释放性能与市售盐酸二甲双胍普通片进行比较，其产品类型丰富，能满足不同患者群体的医用需求。
本产品的胃内漂浮型盐酸二甲双胍(metformin hydrochloride)缓释片,延长盐酸二甲双胍的吸收时间,增加吸收量,改善其生物利用度。盐酸二甲双胍胃漂浮缓释片具有良好的体外漂浮性能和缓释效果,释药行为符合Higuchi方程,释药规律稳定；体内释药平稳,缓释效果良好,基本达到了漂浮制剂延长胃内滞留时间,提高生物利用度的剂型。

Claims (4)

1.一种漂浮膨胀协同型二甲双胍胃滞留片，组成为：二甲双胍、羟丙纤维素、聚氧乙烯、羧甲基纤维素钠，其中，胃滞留时间大于10小时，该滞留片组方为：二甲双胍500mg、羟丙纤维素150mg、聚氧乙烯30mg、羧甲基纤维素钠120mg。
2.一种生物黏附膨胀协同型二甲双胍胃滞留片，组成为：二甲双胍、壳聚糖、共聚维酮、聚氧乙烯以及着色剂和硬脂酸镁，其中，胃滞留时间大于10小时，该滞留片组方为：二甲双胍500mg、壳聚糖45mg、聚氧乙烯225mg、共聚维酮15mg、着色剂和硬脂酸镁15mg。
3.如权利要求1所述的二甲双胍胃滞留片，其特征在于，制备方法为：羟丙纤维素、羧甲基纤维素钠、聚氧乙烯，在压片前分别通过60号筛，然后将混合物用压片机压缩成型，具体压片方法是使用1吨平面冲头对混合物压6秒成形。
4.如权利要求2所述的二甲双胍胃滞留片，其特征在于，制备方法为：聚氧乙烯、壳聚糖、共聚维酮及硬脂酸镁和着色剂，在压片前分别通过60号筛，然后将混合物用压片机压缩成型，具体压片方法是使用1吨平面冲头对混合物压6秒成形。
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