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目的:对米非司酮进行处方前研究,为设计优良的缓释米非司酮阴道环的处方提供依据。方法:采用紫外-可见分光光度法测定米非司酮在水和磷酸盐缓冲液(pH4.0和pH6.8)介质中的溶解度;以差式扫描量热法(DSC)对米非司酮在硅橡胶中的溶解度进行测定;以PVPK30为载体,制备米非司酮固体分散体,并测定其在pH4.0磷酸盐缓冲液中的溶解度;分别考察了含有米非司酮、米非司酮与辅料PVPK30物理混合物及固体分散体的阴道环的体外释放度,以及米非司酮与辅料PVPK30和载体硅橡胶之间的相容性。结果:米非司酮在水和磷酸盐缓冲液介质中于24 h内稳定性良好,在pH4.0磷酸盐缓冲液中的溶解度最大,而米非司酮固体分散体在pH4.0磷酸盐缓冲液中的溶解度则显著增加;米非司酮在硅橡胶中的溶解度为16.80 mg·g-1;载有米非司酮原料药和物理混合物的阴道环无法释放出药物,而含有米非司酮固体分散体的阴道环则能很好地释放药物;米非司酮与辅料PVPK30和硅橡胶的混合物在光照、高温及高湿条件下有关物质未见显著增加。结论:处方前研究表明米非司酮适合制备成阴道黏膜给药系统,固体分散技术是制备米非司酮阴道环的关键技术,它能够使难溶性药物从载体硅橡胶中释放出来。米非司酮与辅料PVPK30和载体硅橡胶之间的相容性良好。
OBJECTIVE: To study prescribing of mifepristone and to provide a basis for the design of a prescription for sustained release of mifepristone vaginal ring. Methods: The solubility of mifepristone in water and phosphate buffer (pH 4.0 and pH6.8) was determined by UV-Vis spectrophotometry. Differential scanning calorimetry (DSC) Solubility in silicone rubber was measured. PVPK30 was used as a carrier to prepare solid dispersion of mifepristone, and its solubility in pH4.0 phosphate buffer was measured. The effects of mifepristone, In vitro release of the vaginal rings of the ketone and excipient PVPK30 physical mixtures and solid dispersions, and compatibility between mifepristone and adjuvant PVPK30 and carrier silicone rubber. RESULTS: Mifepristone was well stable in water and phosphate buffered saline media within 24 h, with maximal solubility in pH 4.0 phosphate buffered saline, and mifepristone solid dispersion at pH 4.0 phosphate The solubility in the buffer was significantly increased; the solubility of mifepristone in the silicone rubber was 16.80 mg · g-1; the vaginal ring containing the mifepristone bulk drug and the physical mixture failed to release the drug, Acetone solid dispersion of the vaginal ring is good for the release of drugs; mifepristone and accessories PVPK30 and silicone rubber mixtures in the light, high temperature and high humidity conditions related substances no significant increase. Conclusion: The pre-prescription study shows that mifepristone is suitable for vaginal mucosal delivery system. Solid dispersion technique is the key technique for preparing mifepristone vaginal ring. It can release insoluble drug from the carrier silicone rubber. Compatibility between mifepristone and excipient PVPK30 and carrier silicone rubber is good.