Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, 71511, Egypt.
Sci Rep. 2024 Sep 29;14(1):22584. doi: 10.1038/s41598-024-71980-5.
The aim of this work is to develop and evaluate self-nanoemulsifying drug delivery systems (SNEDDS) containing simvastatin to increase its oral bioavailability. Formulation EO 5 (Ethyl oleate 9.3% w/w: Tween 80 49.4% w/w: Propylene glycol 39.3% w/w) and Formulation CL 14 (Clove oil 54.3% w/w: Tween 80 34.4% w/w: Transcutol-P 9.3% w/w) were thoroughly studied. They showed emulsification time less than 1 min, droplet size in the nanometric range, and almost a complete drug release after 2 h. The in-vitro dissolution profile of both formulations was found to be significant in comparison to the pure drug in pH 1.2 and 7.4 buffers (P < 0.0001). Furthermore, they demonstrated superior anti-hyperlipidemic activity in comparison to simvastatin suspension (10 mg/kg/day). In order to investigate the impact of oil type on oral bioavailability, the selected formulations have been examined in terms of the in-vivo pharmacokinetic study, and formulation EO 5 was found to have higher bioavailability. After oral administration of a single dose (40 mg/kg) of simvastatin-loaded SNEDDS (CL14 and EO 5), a 1.5-fold and 1.95-fold increase in bioavailability were observed, respectively, as compared to simvastatin suspension. Hence, the results indicated that the developed SNEDDS could enhance the therapeutic efficacy and oral bioavailability of simvastatin.
本工作旨在开发和评价含有辛伐他汀的自微乳给药系统（SNEDDS），以提高其口服生物利用度。制剂 EO5（油酸乙酯 9.3%w/w：吐温 80 49.4%w/w：丙二醇 39.3%w/w）和制剂 CL14（丁香油 54.3%w/w：吐温 80 34.4%w/w：Transcutol-P 9.3%w/w）进行了深入研究。它们表现出乳化时间小于 1 分钟，粒径在纳米范围内，并且在 2 小时后几乎完全释放药物。与纯药物相比，两种制剂在 pH1.2 和 7.4 缓冲液中的体外溶解曲线（P<0.0001）均有显著改善。此外，与辛伐他汀混悬剂（10mg/kg/天）相比，它们表现出更好的抗高血脂活性。为了研究油类型对口服生物利用度的影响，对所选制剂进行了体内药代动力学研究，结果发现制剂 EO5 的生物利用度更高。经口服给予辛伐他汀载药 SNEDDS（CL14 和 EO5）单剂量（40mg/kg）后，与辛伐他汀混悬剂相比，生物利用度分别提高了 1.5 倍和 1.95 倍。因此，结果表明所开发的 SNEDDS 可增强辛伐他汀的治疗效果和口服生物利用度。
