State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, PR China.
Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan.
Drug Dev Ind Pharm. 2021 Jun;47(6):857-866. doi: 10.1080/03639045.2021.1892746. Epub 2021 Jul 21.
This study was aimed at improving the water solubility and oral bioavailability of Chl by self-microemulsifying drug delivery system (Chl-SMEDDS).
Compatibility experiments, pseudo-ternary phase diagram and central composite design were used to optimize the formulation. The selected systems were further evaluated for physical characteristics, including particle size, zeta potential, and appearance. The stability, dispersion test, and intestinal perfusion experiments were used to evaluate the SMEDDS.
The optimal composition of Chl-SMEDDS included: Labrafil M 1944 CS (35%), kolliphor RH 40 (46%), Transcutol HP (19%) and 60 mg/g Chl. The appearance of water emulsified Chl-SMEDDS was green and transparent. The particle size, ζ-potential, and transmission electron microscopy studies showed that spherical globules of Chl-SMEDDS with a size of about 22.82 ± 1.29 nm and a negative surface charge of -24.21 ± 3.45 mV were obtained. Chl-SMEDDS could remain stable at 25 °C and 4 °C for at least 6 months. The dispersion test showed that Chl-SMEDDS dispersed spontaneously to form microemulsion after disintegration of capsule shell and 90% drug dispersed in just 30 min in pH 1.2 HCl without any drug precipitation during the test period. intestinal perfusion experiment revealed that the main absorption site for Chl-SMEDDS was duodenum.
This study indicates that SMEDDS formulation could be an effective strategy for the oral administration of Chl.
本研究旨在通过自微乳药物传递系统（Chl-SMEDDS）来提高 Chl 的水溶性和口服生物利用度。
采用相容性实验、伪三元相图和中心复合设计来优化配方。进一步评估所选系统的物理特性，包括粒径、Zeta 电位和外观。采用稳定性、分散试验和肠灌注实验来评价 SMEDDS。
Chl-SMEDDS 的最佳组成包括：Labrafil M 1944 CS（35%）、Kolliphor RH 40（46%）、Transcutol HP（19%）和 60mg/g Chl。水乳化 Chl-SMEDDS 的外观为绿色透明。粒径、ζ-电位和透射电子显微镜研究表明，Chl-SMEDDS 的球形液滴大小约为 22.82±1.29nm，表面带负电荷-24.21±3.45mV。Chl-SMEDDS 在 25°C 和 4°C 下至少稳定 6 个月。分散试验表明，Chl-SMEDDS 胶囊壳崩解后能自发分散形成微乳，在 pH 1.2 HCl 中 90%的药物在 30min 内分散，试验期间无任何药物沉淀。肠灌注实验表明，Chl-SMEDDS 的主要吸收部位是十二指肠。
本研究表明，SMEDDS 配方可能是 Chl 口服给药的有效策略。
