Choo G-H, Park S-J, Hwang S-J, Kim M-S
Department of Pharmaceutical Engineering, Inje University, Gimhae, Republic of Korea.
Drug Res (Stuttg). 2013 Apr;63(4):203-9. doi: 10.1055/s-0033-1334965. Epub 2013 Mar 13.
This study aimed to develop an effective formulation to improve the solubility and oral absorption of dutasteride by using a self-microemulsifying drug delivery system (SMEDDS). We used the d-optimal mixture design as a tool for developing an optimized SMEDDS formulation with excellent physicochemical characteristics such as mean particle size of <100 nm and percentage of drug dissolved at 15 min, >80%. An optimized dutasteride-loaded SMEDDS formulation consisted of 39.80% CapryolTM 90, 25.90% Cremophor® EL, and 34.30% Transcutol® HP and showed an emulsion droplet size of about 35.3 nm. Approximately 90% of dutasteride from the SMEDDS dissolved at 10 min in dissolution media of pH 1.2 and 6.8. Furthermore, pharmacokinetic studies in rats indicated that compared to the raw drug, the optimized SMEDDS formulation significantly improved the oral absorption of dutasteride. Therefore, preliminary results from our study suggest that the dutasteride-loaded self-microemulsifying formulation has a great potential for clinical application.
本研究旨在通过使用自微乳化药物递送系统（SMEDDS）开发一种有效的制剂，以提高度他雄胺的溶解度和口服吸收。我们使用d-最优混合设计作为工具来开发具有优异物理化学特性的优化SMEDDS制剂，如平均粒径<100 nm以及在15分钟时药物溶解百分比>80%。一种优化的载有度他雄胺的SMEDDS制剂由39.80%的辛酸癸酸甘油三酯（CapryolTM 90）、25.90%的聚氧乙烯蓖麻油（Cremophor® EL）和34.30%的二乙二醇单乙基醚（Transcutol® HP）组成，乳液滴大小约为35.3 nm。在pH 1.2和6.8的溶出介质中，来自SMEDDS的度他雄胺约90%在10分钟时溶解。此外，大鼠体内的药代动力学研究表明，与原料药相比，优化后的SMEDDS制剂显著提高了度他雄胺的口服吸收。因此，我们研究的初步结果表明，载有度他雄胺的自微乳化制剂具有很大的临床应用潜力。
