非洛地平-美托洛尔缓释片处方优化及体外释放一致性评价

Formulation Optimization and Consistency Evaluation of In Vitro Release for Felodipine-metoprolol Sustained-release Tablets

关键词:  非洛地平  美托洛尔  缓释片  处方优化  体外释放  一致性评价

Key words:  felodipine  metoprolol succinate  sustained-release tablets  formulation optimization  in vitro release  consistency evaluation

摘要:

目的 优化非洛地平-美托洛尔缓释片的处方，并评价其与市售制剂体外释放的一致性。方法 采用HPLC测定非洛地平-美托洛尔缓释片中非洛地平及美托洛尔的释放度；以体外释放度为评价指标，重点考察了固体分散体、微丸以及片芯中关键处方因素对非洛地平/美托洛尔释放行为的影响，进一步优化处方。结果 微丸组成、微丸粒径、微丸衣膜中致孔剂用量、微丸增重以及片芯中阻滞剂用量均影响药物释放；处方优化后自制的非洛地平-美托洛尔缓释片与市售制剂在0.3% SDS水溶液、含0.3% SDS的pH 4.0的柠檬酸缓冲液、含0.3% SDS的pH 6.8的磷酸盐缓冲液、含0.3% SDS的0.1 mol·L^-1 HCl中的体外释放行为一致。结论 自制非洛地平-美托洛尔缓释片与市售制剂的体外释放行为一致。

Abstract:

OBJECTIVE To optimize the formulation of felodipine-metoprolol sustained-release tablets and evaluate the consistency of their release in vitro with commercially available preparations. METHODS The release of felodipine and metoprolol was analyzed by HPLC. The influences of crucial factors of solid dispersion, pellets, and tablets on the release of felodipine and metoprolol were investigated and thereby the formulation was optimized. RESULTS The components of pellets, particle size of pellets, amount of porogenic agent in pellet membrane, weight gain of pellets, and amount of retarding agent significantly influenced the in vitro release of felodipine or metoprolol. The release of felodipine and metoprolol from self-made felodipine-metoprolol sustained-release tablets in 0.3% SDS solution, pH 4.0 citrate buffer solution containing 0.3% SDS, pH 6.8 phosphate buffered saline containing 0.3% SDS, and 0.1 μmol·L^-1 HCl containing 0.3% SDS was conformed with that from commercial felodipine-metoprolol sustained-release tablets. CONCLUSION The self-made felodipine-metoprolol sustained-release tablets has the consistent release behaviour with the commercial ones.