基于Franz扩散池法的洛索洛芬钠凝胶贴膏体外释放一致性研究

Study on in Vitro Release Consistency of Loxoprofen Sodium Cataplasms Based on Franz Diffusion Cell Method

关键词:  洛索洛芬钠凝胶贴膏  体外释放  Franz扩散池  一致性评价

Key words:  loxoprofen sodium cataplasms  in vitro release  franz diffusion cell  consistency evaluation

摘要:

目的建立洛索洛芬钠凝胶贴膏体外释放（IVRT）评价方法，考察不同厂家试验制剂和参比制剂释放行为的一致性。方法采用立式改良Franz扩散池，以0.45μm聚醚砜膜为人工膜，12mL脱气后的pH6.8磷酸盐缓冲液为接收介质，转速为500r·min-1，温度为32℃，于0.5，1，2，3，4，5，6，8，10，12h取样12mL并及时补液，以HPLC法分别测定药物的释放量随时间变化的释放规律。分别采用非模型依赖法-相似因子（f2）和非参数法-Mann-Whitney U检验法评价试验制剂与参比制剂体外释放的一致性。结果三家试验制剂与参比制剂的f2因子分别为76.76、84.95、82.00。体外释放速率比值的90%置信区间范围分别为93.49%~104.74%、91.09%~97.62%、90.35%~96.43%，均在90%~111%内，满足CDE要求。结论 三家试验制剂和参比制剂体外释放行为基本一致，所建立的方法可为洛索洛芬钠凝胶贴膏的仿制药一致性评价提供参考。

Abstract:

Objective : To establish an in vitro release ( IVRT ) evaluation method for loxoprofen sodium cataplasms, and to investigate the consistency of release behavior between test preparation and reference preparation from different manufacturers. Methods The vertical modified Franz diffusion cell was used, 0.45 μm polyethersulfone membrane was used as artificial membrane, 12 mL of degassed pH6.8 phosphate buffer solution was used as receiving medium, the rotation speed was 500 r · min-1, the temperature was 32 °C, 12 mL of samples were taken at 0.5,1,2,3,4,5,6,8,10,12 h and replenished in time. The release rule of drug release with time was determined by HPLC.Non-model dependent method-similarity factor (f2) and non-parametric method-Mann-Whitney U test were used to evaluate the consistency of in vitro release between the test preparation and the reference preparation.Results The f2 factors of the three test preparations and reference preparations were 76.76,84.95 and 82.00, respectively.The 90 % confidence interval of the in vitro release rate ratio of the three test preparations and the reference preparations were 93.49 % ~ 104.74 %, 91.09 % ~ 97.62 %, 90.35 % ~ 96.43 %, respectively, all within 90 % ~ 111 %, meeting the CDE requirements. Conclusion The in vitro release behavior of the three test preparations and the reference preparation is basically the same. The established method can provide a reference for the consistency evaluation of generic drugs of loxoprofen sodium cataplasms.