Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Biopharm Drug Dispos. 2021 May;42(5):226-233. doi: 10.1002/bdd.2277. Epub 2021 Apr 23.
The present study was designed to develop a self-emulsifying drug delivery system (SEDDS) of (R)-α-lipoic acid (RLA) to improve the physicochemical and nutraceutical properties of RLA. RLA/SEDDS was prepared using medium-chain triglycerides, Tween 80, and polyethylene glycol 400 as oil, surfactant, and co-surfactant, respectively. The preferable composition of SEDDS was selected according to a pseudo-ternary phase diagram for improved emulsification properties, and its physicochemical and pharmacokinetic properties were evaluated. RLA/SEDDS showed the immediate formation of fine micelles with a mean droplet size of approximately 260 nm when introduced into aqueous media. In simulated gastric fluid, this system could significantly improve the dissolution behavior of RLA and prevent the degradation of RLA, possibly due to the encapsulation of RLA into the emulsion structure. Following the oral administration of RLA/SEDDS (10 mg RLA/kg) in rats, systemic exposure to RLA and dihydrolipoic acid (DHLA), a reduced form of RLA, increased by 7- and 3-fold, respectively. The improved dissolution and gastric stability of RLA could contribute to enhancing systemic exposure to RLA and DHLA after oral administration. From these findings, RLA/SEDDS might be an efficacious dosage option for improving the oral bioavailability as well as nutraceutical properties of RLA.
本研究旨在开发（R）-α-硫辛酸（RLA）的自乳化药物传递系统（SEDDS），以改善 RLA 的物理化学和营养特性。RLA/SEDDS 采用中链甘油三酯、吐温 80 和聚乙二醇 400 分别作为油相、表面活性剂和助表面活性剂制备。根据伪三元相图选择了优选的 SEDDS 组成，以改善乳化性能，并评估了其物理化学和药代动力学性质。RLA/SEDDS 引入水介质时立即形成平均粒径约为 260nm 的细小胶束。在模拟胃液中，该系统可以显著改善 RLA 的溶解行为并防止 RLA 的降解，这可能是由于 RLA 被包封在乳液结构中。在大鼠口服 RLA/SEDDS（10mgRLA/kg）后，RLA 和还原型 RLA 二氢硫辛酸（DHLA）的全身暴露分别增加了 7 倍和 3 倍。RLA 的溶解和胃稳定性的提高可能有助于提高口服后 RLA 和 DHLA 的全身暴露。基于这些发现，RLA/SEDDS 可能是一种有效的剂量选择，可提高 RLA 的口服生物利用度和营养特性。
