基于溶解性、渗透性分析技术的左炔诺孕酮生物药剂学分类及制剂的渗透速率研究

目的： 确定左炔诺孕酮的生物药剂学分类，并比较受试制剂和参比制剂的渗透速率。方法： 分别采用摇瓶法和平行人工膜试验，测定左炔诺孕酮的溶解度和有效渗透性，分析药物的生物药剂学分类特征。采用Macro Flux^TM型药物溶出度与渗透速率测试系统，测定参比制剂和受试制剂的溶出行为及渗透速率，通过关键质量参数，比较受试制剂和参比制剂的差异。结果： 左炔诺孕酮的溶解度为非pH依赖型，属低溶解性药物，在pH 6.8磷酸盐缓冲液中测得的有效渗透性高于美托洛尔，且受试制剂与参比制剂的溶出曲线有较好的相似度，受试制剂的渗透速率和有效吸收的药物总含量分别为参比制剂的88.6%和97.8%。结论： 左炔诺孕酮的生物药剂学分类为BCS第2类和BDDCS第4类，左炔诺孕酮片受试制剂与参比制剂的体外溶出行为和渗透速率基本一致。

Objective: To determine the biopharmaceutical classification of levonorgestrel and compare the permeation rate of the test preparation and the reference preparation. Methods: The solubility and effective permeability of levonorgestrel were determined by shake flask method and parallel artificial membrane test,respectively,and the biopharmaceutical classification characteristics of the drug were analyzed. The Macro Flux^TM drug dissolution and permeation rate test system was used to analyze the dissolution and permeation behavior of the reference preparation and the test preparation,and the differences between them were compared by the key quality parameters. Results: The solubility of levonorgestrel was non-pH dependent and was a low solubility drug. The effective permeability measured in pH 6.8 phosphate buffer was lower than that of metoprolol. The dissolution profile of the test preparation and the reference preparation had a good similarity,and the permeation rate of the test preparation and the total absorbed amount of the drug were 88.6% and 97.8% of the reference preparation,respectively. Conclusion: The biopharmaceutical classification of levonorgestrel is classified into BCS second class and BDDCS fourth class. The in vitro dissolution behavior and permeation rate of the levonorgestrel tablet test preparation and the reference preparation are basically the same.

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