左金胃漂浮-生物粘附小丸的制备配方研究

目的：本研究旨在优选左金胃漂浮-生物粘附小丸的制剂配方。方法：实验以盐酸小檗碱释放度为考察指标，采用星点设计优选左金胃漂浮-生物粘附小丸丸芯的处方组成，以丸芯的圆整度和收率为评价指标，利用正交试验优化挤出滚圆法制备丸芯的工艺参数，丸芯用卡波姆和碳酸氢钠的混合溶液包衣。结果：以羟丙甲纤维素（HPMC K4M）为骨架材料，微晶纤维素（MCC PH301）为成球材料和崩解剂，碳酸氢钠为助漂材料；以挤出速度30r·min^-1，滚圆速度800r·min^-1和滚圆时间20min制备丸芯，包衣后的左金胃漂浮-生物粘附小丸均能在0.1mol·L^-1的盐酸溶液中，在1min内起漂，10h持续漂浮率约80%，生物粘附率83.7%-86.8%，主要成分盐酸小檗碱在12h的累积释放率>90%。结论：左金胃漂浮-生物粘附小丸的累积释放率较高，且在胃内的停留时间延长，制剂配方稳定可靠，为左金丸新剂型的开发和应用提供借鉴。

Study on Pharmaceutical Formulation of Zuo-Jin Gastric Floating-bioadhesive Pellets

This study was aimed to screen out an optimum pharmaceutical formulation of Zuo-Jin(ZJ)gastric floating-bioadhesive pellets.The release degree of berberine hydrochloride was used as index.The central composite design(CCD)was applied in the pellet core optimization of the pharmaceutical formulation of ZJ gastric floating-bioadhesive pellets. Circularity and yield of the pellet core were used as evaluation indexes.Orthogonal test was used in the optimization of technological indexes of pellet core preparation. Mixed solution of carbopol and sodium bicarbonate was used as the coating of pellet core.The results showed that the framework material was HPMC K4M;MCC PH301 was used as the granulation material and disintegrating agent;sodium bicarbonate was used as the floating assisted material.The extruding speed was 30r·min^-1.The spheronization speed was 800r·min^-1and the time was 20min for the pellet core preparation.The ZJ gastric floating-bioadhesive pellets after coating can be floated in the 0.1mol·L^-1hydrochloric acid within 1min.The 10-hour continuous floating rate was about 80%.The biological adhesion rate was 83.7%-86.8%.The 12-hour cumulative release rate of main component berberine hydrochloride was more than 90%.It was concluded that the cumulative release rate of ZJ gastric floating-bioadhesive pellets was relatively high.And its retention time in the stomach was prolonged.The pharmaceutical formulation was stable and reliable.It provided references for the development and application of new pharmaceutical formulations of ZJ pellets.