孕二烯酮缓释微针给药形式的处方前研究

摘要

Objective:To achieve the slow releasing gestodene of microneedles for 7 days by increased the solubility and in vitro dissolution rate under solid dispersion technique,and to provide research evidence for designing dosage form of microneedle sustained released gestodene before prescription.Methods:The solid dispersion was prepared by the solvent evaporation method with PVPK30 as the carrier,and the in vitro dissolution characteristics of gestodene-PVPK30 solid dispersion was determined by IR spectra,X-ray powder diffraction and DSC.And the in vitro transdermal release test was performed on the microneedles prepared by the gestodene solid dispersion.Results:The dissolution rate of gestodene was improved when it was dispersed in solid dispersion.The best proportion of solid dispersion was 1∶4.The average release rate of the solid dispersion in the transdermal release test of gestodene sustained-release microneedles was about 23.97 μg/cm2,which was much greater than that of the drug whose average release rate was 4.48 μg/cm2.Conclusion:The solid dispersion can improve the dissolution rate of gestodene significantly,which can improve the drug release from microneedle delivery system.%目的:通过将孕二烯酮(GEST)制备成固体分散体,提高其溶解度和体外溶出速率,达到微针持续7d缓慢释放的要求,为GEST缓释微针的处方设计提供研究基础.方法:以聚乙烯吡咯烷酮(PVPK30)为载体,溶剂法制备GEST固体分散体,考察其体外溶出特性.同时采用红外光谱法(IR)、X-射线粉末衍射法(XRD)和差示扫描热量法(DSC)考察药物在固体分散体中的存在状态.并对GEST固体分散体制备的微针进行体外透皮释放试验.结果:固体分散体技术大大提高了GEST的溶出速率,最佳比例为1∶4.GEST缓释微针透皮释放试验中固体分散体的平均释药速率为23.97 μg/cm2,原料药的为4.48 μg/cm2,固体分散体的平均释药速率大于原料药.结论:固体分散体技术能显著提高GEST的溶出速率,从而提高药物在微针给药系统中的释放速率.