Abstract

This work aimed to develop controlled-release lipid-based formulations of microemulsion-loaded oleogels for the oral delivery of the poorly soluble drug carvedilol (CARV). The microemulsion-loaded oleogels were prepared by the oleogelator Compritol® 888 (CP888). CARV was loaded into submicron-sized emulsions (CARV-MEs) of various ratios of surfactant and cosurfactant. The CARV-MEs were entrapped into CP888-based oleogels, forming CARV-ME oleogels. The rheological properties and dissolution studies of the CARV-ME oleogels were determined. MTT assay test was performed to ensure the safety of oleogel formulations. The optimized formulation of CARV-ME oleogel was subjected to stability studies. The results revealed that CARV-MEs were thermodynamically stable of spherical globules of average size 13.3–57.4 nm, polydispersity index (PDI) range of 0.24–0.52, and interfacial tension of 29.9 ± 0.2 mN/m. Oleogels exhibited viscoelastic properties with more elastic behavior. The drug release rate was found to be dependent on the surfactant/cosurfactant ratio. A negative correlation was found between surfactant concentration and IC₅₀. The optimized CARV-MEs oleogel was stable for 3 months at various storage conditions. In conclusion, the entrapment of the CARV-MEs, with various surfactant to cosurfactant ratios, into oleogels influences the dissolution rate and mechanism of drug release and the safety of CARV-MEs oleogels.

摘要

这项工作旨在开发用于口服递送难溶性药物卡维地洛 (CARV) 的微乳油凝胶控释脂质制剂。载有微乳液的油凝胶由油胶凝器 Compritol® 888 (CP888) 制备。CARV 被加载到各种比例的表面活性剂和辅助表面活性剂的亚微米级乳液 (CARV-ME) 中。CARV-ME 被包裹在基于 CP888 的油凝胶中，形成 CARV-ME 油凝胶。确定了 CARV-ME 油凝胶的流变学特性和溶解度研究。进行 MTT 测定测试以确保油凝胶制剂的安全性。对 CARV-ME 油凝胶的优化配方进行了稳定性研究。结果表明，CARV-ME 是热力学稳定的球形小球，平均尺寸为 13.3-57.4 nm，多分散指数 (PDI) 范围为 0.24-0。52，界面张力为 29.9 ± 0.2 mN/m。油凝胶表现出具有更多弹性行为的粘弹性。发现药物释放速率取决于表面活性剂/辅助表面活性剂的比例。发现表面活性剂浓度与 IC 呈负相关₅₀。优化后的 CARV-MEs 油凝胶在各种储存条件下可稳定 3 个月。总之，将具有各种表面活性剂与助表面活性剂比例的 CARV-ME 包埋到油凝胶中会影响溶出速率和药物释放机制以及 CARV-ME 油凝胶的安全性。