度他雄胺自微乳口腔膜剂的制备及其体内外评价

Preparation and in vitro and in vivo evaluation of Dutasteride self-microemulsions oral films

目的制备度他雄胺自微乳口腔膜剂,并进行体内外评价。方法用溶剂浇铸法制备度他雄胺自微乳口腔膜剂,考察其外观、崩解时间、体外溶出度、粒径等指标;比较自制的度他雄胺口腔膜剂(受试制剂)与度他雄胺软胶囊(参比制剂)在Beagle犬体内的药动学特征。结果自制的度他雄胺自微乳口腔膜剂的外观光滑平整,崩解时间为26±2 s,体外溶出度在20 min时即可达87%±0.5%,平均粒径为147.9 nm,跨距0.83;受试制剂与参比制剂的AUC_(0-t)分别为2.7838±0.7570、2.8866±0.8297μg·m L^(-1)·h,AUC_(0-∞)分别为2.8831±0.8646、2.8914±0.6299μg·m L^(-1)·h,t_(1/2)分别为45.8±10.4、42.2±14.9 h,t_(max)分别为3.8±3.6、4.1±1.2 h,C_(max)分别为46.1±3.3、45.3±8.5 ng·m L^(-1)。结论度他雄胺自微乳口腔膜剂不仅保持了液体自微乳的特性,且能提高患者的顺应性。

OBJECTIVE To prepare Dutasteride self - microemulsion oral films （DSOF） and evaluate it in vitro and in vivo. METH- ODS Solvent casting method was used to prepare DSOF. The appearance, disintegrate time, in vitro dissolution, particle size and other indicators were studied. The results of pharmaeokinetic studies of DSOF（ test preparation） and Dutasteride soft capsules（ reference prep- aration） in Beagle dogs were compared. RESULTS The appearance of DSOF was smooth. The disintegrate time was 26 ± 2 s and the cumulative release percentage in vitro dissolution achieved 87%±0.5% in 20 min. The average particle size was 147.9 nm and the span was 0. 83. The pharmacokinetic parameters of the test preparation and reference preparation were as follows： AUC0-1 was 0.27838 ±0. 7570 μg·mL^-1·h and 0. 28866±0. 8297 p,g· mL^-1·h;AUC0-∞ was 0. 28831 ± 0. 8646 μg·mL^-1·h and 2. 8914 ± 0.6299 μg·mL^-1·h;t1/2 was 45.8 ± 10.4 h and 42.2 ± 14.9 h;tmax Was 3.8±3.6 h and 4.1±1.2 h;Cmax was 46.1±3.3 ng·mL^-1 and 45.3± 8.5 ng·mL^-1. CONCLUSION DSOF not only maintains the characteristics of the liquid self - microemulsions, but also improve the patients＇ compliance.