利用专家系统和人工神经网络开发格列吡嗪推拉式渗透泵控释片  

Development of glipizide push-pull osmotic pump controlled release tablets by using expert system and artificial neural network

作　　者：张志宏[1,2,3] 王悦[1,2] 吴文芳[4] 赵曦[1,2] 孙晓翠[1,2] 王焕青[1] 

机构地区：[1]石药集团中奇制药技术(石家庄)有限公司 [2]石药集团新型药物制剂与新辅料国家重点实验室 [3]Austar Pharma,Edison,NJ 08837,USA [4]石药集团有限公司

出　　处：《药学学报》2012年第12期1687-1695,共9页Acta Pharmaceutica Sinica

基　　金：科技部"十一五"重大新药创制资助项目(2010ZX09401-402);国家科技重大专项资助项目(2011ZX09203-002);国家重点基础研究发展计划资助项目(2012CB724002)

摘　　要：本文目的在于利用专家系统和人工神经网络开发格列吡嗪推拉式渗透泵控释片。首先以瑞易宁实测释放度结果为目标,利用难溶性药物渗透泵处方设计专家系统设计处方;再根据系统给出的处方制备样品并利用体外释放度进行实验验证,并与瑞易宁进行动物体内药代动力学对比;最后利用人工神经网络对能影响产品释放的处方工艺范围进行优化和设计空间确定。结果发现,利用专家系统可以在极短时间内获得所需要的产品处方,其体外释放与市售制剂相似,与瑞易宁在Beagle犬体内生物等效,关键参数设计空间为包衣增重9.5%～12.0%。开发产品制定的释放度质量标准高于进口注册标准,利用人工智能的手段开发出质量优良的格列吡嗪控释片。The purpose of this study is to develop glipizide push-pull osmotic pump （PPOP） tablets by using a formulation design expert system and an artificial neural network （ANN）. Firstly, the expert system for the formulation design of osmotic pump of poor water-soluble drug was employed to design the formulation of glipizide PPOP, taking the dissolution test results of Glucotrol XL as the goal. Then glipizide PPOP was prepared according to the designed formulations and the in vitro dissolution was carried out. And in vivo evaluation was carried out between the samples which were similar to Glucotrol XL and the Glucotrol XL in Beagle dogs. The range of the factors of formulation and procedure, which could influence the drug release, was optimized using artificial neural network. Finally, the design space was found. It was found that the target formulation which was similar to Glucotrol XL in dissolution test could be obtained in a short period by using the expert system. The samples which were similar to Glucotrol XL were bio-equivalent to the Glucotrol XL in Beagle dogs. The design space of the key parameter coating weight gain was 9.5%-12.0%. It could be concluded that a well controlled product of glipizide PPOP was developed since the dissolution test standard of our product was more strict than that of Glucotrol XL.

关 键 词：渗透泵 专家系统 格列吡嗪 难溶性药物 控释 

分 类 号：R943[医药卫生—药剂学]