Department of Pharmaceutics, College of Pharmacy, King Khalid University, Guraiger, Abha, 62529, Saudi Arabia.
Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, 570015, India.
AAPS PharmSciTech. 2020 May 13;21(4):129. doi: 10.1208/s12249-020-01666-4.
Simvastatin a cholesterol-lowering agent used to treat hypercholesterolemia, coronary heart disease, and dyslipidemia. However, simvastatin (SV) has shown low oral bioavailability in GIT. The main purpose of the work was to develop proliposomal formulations to increase the oral bioavailability of SV. Film deposition on the carrier method has been used to prepare the proliposomes. The proliposomes were assessed for morphology, particulate size, entrapment efficacy, drug-polymer compatibility, in vitro and in vivo studies. FTIR and DSC results revealed no drug-polymer interaction. SEM and XRD analysis conform; proliposomes are spherical, amorphous in nature, so that it enhances the solubility of SV between 15.01 ± 0.026 and 57.80 ± 0.015 μg/mL in pH 7.4 phosphate buffer. The optimised formulation (PL6) shows drug release up to 12 h (99.78 ± 0.067%). The pharmacokinetics of pure SV and SV proliposomes (SVP) in rats were T 2 ± 0.5 and 4 ± 0.7 h, C 10.4 ± 2.921 and 21.18 ± 12.321 μg/mL, AUC0-∞ 67.124 ± 0.23 and 179.75 ± 1.541 μg/mL h, respectively. Optimised SVP shows a significant improvement in the rate and absorption of SV. The optimised formulation showed enhanced oral bioavailability of SV in Albino Wister rats and offers a new technique to improve the poor water-soluble drug absorption in the gastrointestinal system.
辛伐他汀是一种用于治疗高胆固醇血症、冠心病和血脂异常的降脂药物。然而，辛伐他汀（SV）在胃肠道中的口服生物利用度较低。这项工作的主要目的是开发前体脂质体制剂来提高 SV 的口服生物利用度。采用载体膜沉积法制备前体脂质体。对前体脂质体的形态、粒径、包封率、药物-聚合物相容性、体外和体内研究进行了评估。FTIR 和 DSC 结果表明无药物-聚合物相互作用。SEM 和 XRD 分析证实前体脂质体为球形，无定形，从而提高了 SV 在 pH 7.4 磷酸盐缓冲液中的溶解度，范围在 15.01±0.026 至 57.80±0.015μg/mL 之间。优化的配方（PL6）显示药物释放可达 12 小时（99.78±0.067%）。纯 SV 和 SV 前体脂质体（SVP）在大鼠体内的药代动力学参数分别为 T 2±0.5 和 4±0.7 h，C 10.4±2.921 和 21.18±12.321μg/mL，AUC0-∞ 67.124±0.23 和 179.75±1.541μg/mL·h。优化后的 SVP 显著提高了 SV 的吸收速率和吸收程度。优化后的配方在白化 Wistar 大鼠中显示出辛伐他汀口服生物利用度的显著提高，为改善胃肠道系统中水溶性差的药物吸收提供了一种新技术。
