盐酸青藤碱胃滞留型择时释药片的研制

目的:研制盐酸青藤碱胃滞留型择时释药片,考察处方和工艺因素对其体外释药的影响,解析其释放机制.方法:以盐酸青藤碱为模型药物采用压制包衣法制得胃滞留型择时释药片;以膨胀率和释药时滞为指标,筛选片芯用崩解剂;通过体外药物释放试验,考察影响择时释药片漂浮性能和释药时滞的包衣处方和工艺因素;通过溶蚀试验探讨其释药机制.结果:体外释放时,盐酸青藤碱胃滞留型择时释药片经一定时滞后药物均呈脉冲释放.片芯选用羧甲基淀粉钠作为崩解剂;随包衣处方中羟丙甲纤维素与卡拉胶的比例和凝胶材料用量增加,释药时滞延长;包衣压片压力和衣膜材料制备工艺对时滞无显著影响;释药机制为衣膜溶蚀和片芯溶胀协同作用.结论:盐酸青藤碱胃滞留型择时释药片经一定时滞后药物呈脉冲释放,调节其包衣处方可获得具有适当时滞的择时给药系统,满足时辰治疗要求.

Preparation of gastric retenting and chronopharmacologic drug delivery tablets of sinomenine hydrochloride

Objective: To prepare the gastric retenting and chronopharmacologic drug delivery tablets containing sinomenine hydrochloride as a model drug, evaluate the effects of the coating layers formulation and technics on drug release behavior, and to elucidate the mechanism of drug release based on obtained results.  Method: The gastric retenting and chronopharmacologic drug delivery tablets were prepared by press coated technics. The types of disintegrants were chosen according to the expanding rate and the lag time. The effects of formulation and technics of coating layer on the release characteristic of the drug were investigated by dissolution testing. The mechanism of drug release was proved by erosion test.  Result: The tablets had typical chronopharmacologic drug delivery properties with a lag time followed by a rapid release phase. CMS Na was selected as the disintegrant. The lag time was prolonged with the increase of the ratio of HPMC/carrrageenan and the amount of matrix material in coating layer. The compressing pressure and preparation method of coat material had minor influence on the lag time of the tablets. Coating layer erosion and tablet core swelling were involved in the mechanism of drug release.   Conclusion: The tablets had typical chronopharmacologic drug delivery properties. A suitable lag time can be achieved by adjusting formulation of coating layer to meet the requirement of chronotherapy.