熔融法制粒制备难溶性药物卡马西平缓释片

发布时间：2019-03-08 22:04

【摘要】：本文主要研究熔融制粒辅料的各种处方变量和工艺参数对药物释放的影响，，为山嵛酸甘油酯（Compritol888ATO）用于熔融法制粒制备难溶性药物的缓释片剂时提供一些参考数据，从而为今后该辅料用于热熔融制粒的产业化提供技术支持和应用指导。根据热熔融制粒的原理，自行设计组装实验室熔融制粒设备。以卡马西平（carbamazepine，CBZ）为模型药物，山嵛酸甘油酯为可熔融阻滞材料，考察其单独应用，以及与不同粘度羟丙甲纤维素（hydroxypropylmethylcellulose，HPMC）联合应用后，对难溶性药物体外释放的影响；比较湿法制粒、熔融法制粒和粉末直压3种方法制备的缓释片的累积释放度差异；以f2值评价当日制备的卡马西平缓释片和存放30天后的缓释片体外释放度是否存在差异。结果指出，单独应用山嵛酸甘油酯时，调节乳糖与山嵛酸甘油酯的比例，卡马西平24h后累积释放度不超过40%；山嵛酸甘油酯与HPMC联合应用时，随着山嵛酸甘油酯的比例和HPMC粘度的降低，卡马西平释放速度呈增加趋势；熔融法制粒压片制备的缓释片12h释放70%，24h后释放超过95%，湿法制粒压片和粉末直压压片制备的片剂12h就释放90%以上；与当天制备的缓释片相比，缓释片存放3天、7天和30天后，f2值分别为82.72、72.87、76.00。由此可以得出，卡马西平的释放速度与山嵛酸甘油酯在处方中占的比例呈负相关；与单独应用山嵛酸甘油酯相比，处方中加入HPMC后更有利于卡马西平的释放；与湿法制粒和粉末直压法相比，熔融法制粒压片所产生的阻滞效果更强，在一定程度上可以用最少的辅料达到最佳的释放效果，有利于减少制剂成本；从f2值可以看出，存放30天后的缓释片与当天制备出来的缓释片相比，f2值仍大于50，说明存放30天对片剂的释放度影响不大。
[Abstract]:In this paper, the effects of various prescription variables and technological parameters on drug release were studied in order to provide some reference data for the preparation of sustained-release tablets of insoluble drugs by melt granulation of glyceryl behenate (Compritol888ATO). It can provide technical support and application guidance for the industrialization of hot melt granulation in the future. According to the principle of hot melt granulation, the melting granulation equipment was designed and assembled in laboratory. The effects of carbamazepine (carbamazepine,CBZ) on the release of insoluble drugs in vitro were investigated by using carbamazepine (hydroxypropylmethylcellulose,HPMC) as a model drug and glyceride as a melting block material, and combined with different viscosity of hydroxypropyl methylcellulose (hydroxypropylmethylcellulose,HPMC). The cumulative release of sustained-release tablets prepared by wet granulation, melt granulation and powder direct pressing was compared, and the in vitro release of carbamazepine sustained-release tablets prepared on the same day and stored for 30 days was evaluated by F2 value. The results showed that the cumulative release of carbamazepine was not more than 40% after 24 hours of carbamazepine when the ratio of lactose to behenate was adjusted when glyceride was used alone. The release rate of carbamazepine increased with the decrease of the ratio and viscosity of HPMC and the ratio of glyceryl behenate in combination with HPMC. The sustained-release tablets prepared by melt granulation released 70% at 12 h and over 95% after 24 h, while those prepared by wet granulation tablet and powder direct compression tablet released more than 90% at 12 h. Compared with the sustained-release tablets prepared on the same day, the f2 values of the sustained-release tablets stored for 3 days, 7 days and 30 days were 82.72, 72.87, 76.00, respectively. It can be concluded that the release rate of carbamazepine is negatively correlated with the proportion of methanolic glyceride in the prescription, and the release of carbamazepine is more favorable to carbamazepine release after the addition of HPMC than that of behenate alone. Compared with wet granulation and powder direct pressing, the blocking effect of melt granulation tablet is stronger, and the best release effect can be achieved with the least auxiliary material to a certain extent, which is helpful to reduce the preparation cost. It can be seen from the f2 value that the f2 value of the sustained-release tablets stored for 30 days is still higher than that of the sustained-release tablets prepared on the same day, indicating that 30 days storage has little effect on the release degree of the tablets.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943

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