硝苯地平控释片体内外相关性溶出方法研究

Study on Correlation Dissolution Method of Nifedipine Controlled-release Tablets In Vitro and In Vivo

关键词:  流池法|难溶性药物|溶出|区分性|体内外相关

Key words:  flow through cell|poorly soluble drug|dissolution|discriminatory|in vitro and in vivo correlation

摘要:

目的 开发相应的能区分和反映参比制剂与自研制剂之间释放差异的溶出方法，使自研制剂与参比制剂体外释放达到最大程度的匹配，从而为生物等效性试验提供体内外更具相关性的研究。方法 采用美国药典(USP)溶出2法(桨法)作为质量控制方法；另采用流池法作为溶出区分性方法，评估不同实验参数下的溶出结果。结果 优化并确立方法为开环系统，流速3.0 mL·min^-1，加1/2勺玻璃珠。该方法可以有效区分处方和生产工艺变化对产品溶出的影响。以此法为基础所得到的体外溶出速率和溶出度与体内药动学研究结果一致。结论 本研究所开发的流池法适合作为硝苯地平控释片的溶出区分性方法，并具备一定的体内体外相关性。

Abstract:

OBJECTIVE To develop corresponding dissolution methods that can distinguish and reflect the release difference between the reference preparation and the self-developed preparation, so as to maximize the matching of the in vitro release of the self-developed preparation and the reference preparation, thus to provide more relevant research in vivo and in vitro for bioequivalence test METHODS USP(United States Pharmacopoeia) dissolution method 2(paddle method) was used as the quality control method; In addition, the flow cell method was used as the dissolution differentiation method to evaluate the dissolution results under different experimental parameters. RESULTS the method was determined as an open-loop system with a flow rate of 3.0 mL·min^-1 and 1/2 spoon of glass beads. This method could effectively distinguish the influence of prescription and production process changes on product dissolution. The dissolution rate and dissolution rate obtained based on this method were consistent with the results of pharmacokinetics study in vivo. CONCLUSION The established flow-through cell method is suitable for discriminatory testing of the nifedipine controlled-release tablets.