CN112618511A - 一种非诺贝特胶囊的处方组成及制备工艺 - Google Patents
一种非诺贝特胶囊的处方组成及制备工艺 Download PDFInfo
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Abstract
本发明公开了一种非诺贝特胶囊的处方组成和制备工艺。所述的非诺贝特胶囊由30‑70％质量含量的活性成分非诺贝特和余量的药用辅料组成；所述非诺贝特的原料经微粉化处理，粒径≤30μm；所述药用辅料包括填充剂、崩解剂、润湿剂、黏合剂、表面活性剂、润滑剂中的一种或几种。本发明设计的非诺贝特胶囊的处方组成和制备工艺，包含多种溶出改善策略，工艺优化，可制备出溶出迅速、稳定性高的非诺贝特胶囊。
Description
技术领域
本发明属于医药制剂技术领域，具体涉及一种非诺贝特胶囊的处方组成及制备工艺。
背景技术
非诺贝特，其化学名为2-(4-(4-氯苯甲酰基)苯氧基)-2-甲基丙酸异丙酯，分子式为C20H21ClO4，分子量为360.84。它是苯氧乙酸类降血脂药，在体内被迅速、完全水解为活性代谢产物非诺贝特酸，增加脂蛋白脂酶活性，促进三酰甘油代谢，降低总胆固醇、三酰甘油与低密度脂蛋白的浓度，增加高密度脂蛋白含量。其作用机制有两个方面：①抑制羟甲基戊二酸单酰辅酶A(HMG—CoA)还原酶而减少胆固醇的合成；②增加脂蛋白酯酶和肝酯酶的活性而加快三酰甘油的清除以及增加高密度脂蛋白—胆固醇的水平。研究表明，非诺贝特不仅具有抗凝血、促进纤溶等抗动脉粥样作用，还有预防急性心肌及脑组织缺血性损伤、改善胰岛素抵抗、治疗糖尿病及其并发症等调脂以外的作用。
非诺贝特为白色或类白色结晶性粉末，极易溶于氯仿，易溶于丙酮或乙醚，溶于乙醇，几乎不溶于水，是一种亲脂性化合物。非诺贝特在体内的生物利用度极低，影响其临床疗效的发挥，因此需要采用制剂技术加快溶出速度，促进其在体内的吸收，进而提高药物疗效。在非诺贝特胶囊制备过程中，如何有效加快非诺贝特的溶出速度是制剂研发的着力点。
发明内容
本发明的目的是提供一种非诺贝特胶囊的处方组成和制备工艺。
本发明所述的非诺贝特胶囊由30-70％质量含量的活性成分非诺贝特和余量的药用辅料组成；所述非诺贝特的原料经微粉化处理，粒径≤30μm；所述药用辅料包括填充剂、崩解剂、润湿剂、黏合剂、表面活性剂、润滑剂中的一种或几种。
所述填充剂在胶囊中的质量含量为5-30％，具体选自蔗糖、乳糖、糊精、淀粉、微晶纤维素、碳酸钙、甘露醇中的一种或几种。
所述崩解剂在胶囊中的质量含量为5-30％，具体选自羧甲基淀粉钠、交联羧甲纤维素钠、交联聚维酮、低取代羟丙纤维素中的一种或几种。
所述润湿剂为水和/或乙醇。
所述黏合剂在胶囊中的质量含量为5-20％，具体选自淀粉、预胶化淀粉、聚维酮、甲基纤维素、羟丙纤维素、乙基纤维素中的一种或几种。
所述表面活性剂在胶囊中的质量含量为1-5％，具体选自十二烷基硫酸钠、吐温80、泊洛沙姆中的一种或几种。
所述润滑剂在胶囊中的质量含量为0.1-5％，具体选自硬脂酸镁、滑石粉、聚乙二醇中的一种或几种。
所述胶囊还包含0.1-3wt％的胶态二氧化硅。
本发明设计的非诺贝特胶囊的处方组成和制备工艺，包含多种溶出改善策略，工艺优化，可制备出溶出迅速、稳定性高的非诺贝特胶囊。
附图说明
图1为实施例与参比制剂的溶出曲线图。
具体实施方式
本发明的实施例仅为了对本发明进行解释和说明，不应理解为对本发明的任何限制。
实施例1
处方：
制备工艺：
(1)将非诺贝特进行微粉化处理；
(2)将非诺贝特、乳糖、羧甲基淀粉钠、预胶化淀粉置于混合器中混合15min；
(3)采用50％乙醇溶液溶解十二烷基硫酸钠，于湿法制粒机中制得干湿均匀的软材，过20目筛制粒，在55℃条件下干燥，测得水分为1.59％；
(4)所得颗粒与胶态二氧化硅混合3min，再加入硬脂酸镁混合2min；
(5)将所得颗粒装填1#胶囊。
实施例2
处方：
制备工艺：
(1)将非诺贝特进行微粉化处理；
(2)将非诺贝特、微晶纤维素、交联聚维酮、交联羧甲纤维素钠置于混合器中混合10min；
(3)采用50％乙醇溶液溶解聚维酮和十二烷基硫酸钠，于湿法制粒机中制得干湿均匀的软材，过20目筛制粒，在55℃条件下干燥，测得水分为1.43％；
(4)所得颗粒与胶态二氧化硅混合2min，再加入硬脂酸镁混合2min；
(5)将所得颗粒装填1#胶囊。
实施例3
处方：
制备工艺：
(1)将非诺贝特进行微粉化处理；
(2)将非诺贝特、乳糖、交联聚维酮、交联羧甲纤维素钠、预胶化淀粉置于混合器中混合20min；
(3)采用50％乙醇溶液溶解泊洛沙姆，于湿法制粒机中制得干湿均匀的软材，过20目筛制粒，在55℃条件下干燥，测得水分为1.12％；
(4)所得颗粒与胶态二氧化硅混合3min，再加入硬脂酸镁混合2min；
(5)将所得颗粒装填1#胶囊。
对上述各实施例制得的非诺贝特胶囊和参比制剂进行溶出曲线检测，测定结果如表1，溶出曲线如图1。根据《普通口服固体制剂溶出曲线测定与比较指导原则》，采用桨法，以0.025M的十二烷基硫酸钠溶液(1000ml)为溶出介质，转速为每分钟75转，分别在5min、10min、15min、20min、30min、45min、60min、90min、120min时间点取样，检测其溶出度。
表1：各实施例样品和参比制剂的溶出测定结果
从溶出检测结果和溶出曲线(图1)可知，本发明各实施例制备的非诺贝特胶囊溶出良好，与参比制剂溶出曲线基本一致。快速溶出的非诺贝特胶囊利于在体内的吸收，从而提高生物利用度。
对各实施例制得的非诺贝特胶囊和参比制剂在加速条件下的有关物质进行测定，测定结果如表2。
表2：各实施例样品和参比制剂的有关物质测定结果
注：加速条件为40℃±2℃/75％RH±5％RH。
从表2中可知，本发明各实施例制备的非诺贝特胶囊与参比制剂相比，杂质含量较低，稳定性得到提高。
Claims (8)
1.一种非诺贝特胶囊，其特征在于，所述胶囊由30-70％质量含量的活性成分非诺贝特和余量的药用辅料组成；所述非诺贝特的原料经微粉化处理，粒径≤30μm；所述药用辅料包括填充剂、崩解剂、润湿剂、黏合剂、表面活性剂、润滑剂中的一种或几种。
2.根据权利要求1所述的非诺贝特胶囊，其特征在于，所述填充剂在胶囊中的质量含量为5-30％，具体选自蔗糖、乳糖、糊精、淀粉、微晶纤维素、碳酸钙、甘露醇中的一种或几种。
3.根据权利要求1所述的非诺贝特胶囊，其特征在于，所述崩解剂在胶囊中的质量含量为5-30％，具体选自羧甲基淀粉钠、交联羧甲纤维素钠、交联聚维酮、低取代羟丙纤维素中的一种或几种。
4.根据权利要求1所述的非诺贝特胶囊，其特征在于，所述润湿剂为水和/或乙醇。
5.根据权利要求1所述的非诺贝特胶囊，其特征在于，所述黏合剂在胶囊中的质量含量为5-20％，具体选自淀粉、预胶化淀粉、聚维酮、甲基纤维素、羟丙纤维素、乙基纤维素中的一种或几种。
6.根据权利要求1所述的非诺贝特胶囊，其特征在于，所述表面活性剂在胶囊中的质量含量为1-5％，具体选自十二烷基硫酸钠、吐温80、泊洛沙姆中的一种或几种。
7.根据权利要求1所述的非诺贝特胶囊，其特征在于，所述润滑剂在胶囊中的质量含量为0.1-5％，具体选自硬脂酸镁、滑石粉、聚乙二醇中的一种或几种。
8.根据权利要求1所述的非诺贝特胶囊，其特征在于，所述胶囊还包含0.1-3wt％的胶态二氧化硅。
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