氨茶碱片的实时溶出度相似性分析研究

Comparison study on monitoring the dissolution process of aminophylline tablets

目的:考察不同厂家生产的氨茶碱片体外实时溶出曲线,比较各厂家之间及与日本橙皮书中氨茶碱片溶出曲线之间的差异,分析现行溶出度方法的质量可控性及各厂家处方设计合理性,为进一步加强"治疗窗"狭窄类药物的质量控制及处方设计提供思路及有效手段,也为合理制定氨茶碱片溶出度方法提供依据。方法:采用光纤药物溶出度实时测定仪,测定各厂家氨茶碱片在水、pH 1.2、pH 4.0和pH 6.8缓冲溶液这4种溶出介质中的实时溶出曲线。结果:31家企业的氨茶碱片在5 min时的溶出量均大于40%,均产生突释;部分厂家的氨茶碱片在4种溶出介质中实时溶出行为差异较大,内在质量存在较大差异,且部分生产企业生产的氨茶碱片批内均一性较差,工艺不稳定,产品质量不均一。结论:对于氨茶碱片这类"治疗窗"狭窄类药物,溶出度单点控制法不能满足要求,不能有效地监控产品质量。国内绝大部分氨茶碱片生产企业在处方工艺设计时未考虑本品属于"治疗窗"狭窄药物,处方设计不合理。对于"治疗窗"狭窄类药物质量及安全性应进行再评价,以保证此类药物的安全有效。

Objective：To compare the qualities of aminophylline tablets from different manufactures with fiber-optic in situ dissolution testing method,analysis the rationality of the dissolution method and the description designs of different manufactures,so as to establish a valuable means to improve the quality control of narrow therapeutic range drugs.Methods：The dissolution curves of Aminophylline tablets from different manufactures in water,pH 1.2,4.0,and 6.8 buffer were determined with fiber-optic in situ dissolution tester.Results：The dissolution of aminophylline tablets from 31 different manufactures in 5 minutes is all above 40%.Moreover,obvious difference was observed in the same batch of tablets from some domestic manufactures.These results indicated that the quality of domestic aminophylline tablets is heterogeneity.Conclusion：For narrow therapeutic range drugs as aminophylline tablets,it is impossible to test the dissolution by using single time method,and difficult to completely control the quality.Most of the aminophylline tablets manufactures haven＇t realized that aminophylline tablets are narrow therapeutic range drugs,so the description designs are irrational.We should reassess the security of narrow therapeutic range drugs to improve their security and efficiency.