College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
Department of Psychology, York University, Toronto, Ontario, Canada.
Pharm Dev Technol. 2023 Jun;28(5):479-491. doi: 10.1080/10837450.2023.2208206. Epub 2023 May 5.
To enhance the oral bioavailability of atorvastatin calcium (ATV), a novel solidified micelle (S-micelle) was developed. Two surfactants, Gelucire 48/16 (G48) and Tween 20 (T20), were employed for micelle formation, and two solid carriers (SC), Florite PS-10 (FLO) and Vivapur 105 (VP105), were selected as solid carriers. The S-micelle was optimized using a Box-Behnken design with three independent variables, including G48:T20 (, 1.8:1), SC:G48 + T20 (, 0.65:1), and FLO:VP105 (, 1.4:0.6), resulting in a droplet size () of 198.4 nm, dissolution efficiency at 15 min in the pH 1.2 medium () of 47.6%, Carr's index () of 16.9, and total quantity () of 562.5 mg. The optimized S-micelle resulted in good correlation showing percentage prediction values less than 10%. The optimized S-micelle formed a nanosized dispersion in the aqueous phase, with a higher dissolution rate than raw ATV and crushed Lipitor®. The optimized S-micelle improved the relative bioavailability of oral ATV (25 mg equivalent/kg) in rats by approximately 509 and 271% compared to raw ATV and crushed Lipitor, respectively. In conclusion, the optimized S-micelle possesses great potential for the development of solidified formulations for improved oral absorption of poorly water-soluble drugs.
为了提高阿托伐他汀钙（ATV）的口服生物利用度，开发了一种新型固态胶束（S-胶束）。使用两种表面活性剂，Gelucire 48/16（G48）和吐温 20（T20）形成胶束，选择两种固体载体（SC），Florite PS-10（FLO）和 Vivapur 105（VP105）作为固体载体。使用三因素 Box-Behnken 设计优化 S-胶束，包括 G48：T20（，1.8：1）、SC：G48+T20（，0.65：1）和 FLO：VP105（，1.4：0.6），结果粒径（）为 198.4nm，在 pH 1.2 介质中 15 分钟的溶解效率（）为 47.6%，Carr 指数（）为 16.9%，总量（）为 562.5mg。优化后的 S-胶束显示出良好的相关性，预测值百分比小于 10%。优化后的 S-胶束在水相中成纳米分散体，比原 ATV 和粉碎的 Lipitor®具有更高的溶解速率。与原 ATV 和粉碎的 Lipitor 相比，优化后的 S-胶束使口服 ATV（25mg 当量/kg）的相对生物利用度在大鼠中分别提高了约 509%和 271%。总之，优化后的 S-胶束为改善难溶性药物的口服吸收而开发固态制剂具有很大的潜力。
