曲马多在 TPGS 胶束中的增溶作用：温度和电解质添加的影响。

Solubilization of Carbamazepine in TPGS Micelles: Effect of Temperature and Electrolyte Addition.

机构信息

Maliba Pharmacy College, UKA Tarsadia University, Gopal-Vidyanagar Campus, Surat, Gujarat, 394350, India.

Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra, 400085, India.

出版信息

AAPS PharmSciTech. 2019 May 28;20(5):203. doi: 10.1208/s12249-019-1412-1.

DOI:10.1208/s12249-019-1412-1

PMID:31139965

Abstract

D-α-Tocopheryl polyethylene glycol succinate (TPGS), a polyethylene glycol condensate, is a biologically important nonionic amphiphile. In this study, we report on aqueous solution behavior of TPGS with a focus on its clouding, surface activity, micellar characteristics, and solubilization capacity for a model hydrophobic drug, carbamazepine (CBZ). Micelles were characterized by dynamic light and small-angle neutron scattering studies as a function of temperature, salt addition, and CBZ solubilization. TPGS showed a cloud point of 78°C and possessed good surface activity (as observed from surface tension reduction and adsorption parameters). The critical micelle concentration (CMC), obtained from surface tension and fluorescence studies, was 0.02 mM. Scattering studies showed formation of stable micelles (average diameter-12 nm), exhibiting no significant changes in size upon salt addition (up to 1 M NaCl), CBZ incorporation (up to 5 mM), and temperature increase (40°C). Micelles in 5 wt% TPGS showed about twentyfold enhancement in CBZ solubility. Considering the remarkable CBZ solubilization and its positioning in the core, we suggest that the formulation can be exploited as a sustained delivery vehicle.

摘要

D-α-生育酚聚乙二醇琥珀酸酯（TPGS），一种聚乙二醇缩合物，是一种生物学上重要的非离子两亲性物质。在这项研究中，我们报告了 TPGS 在水溶液中的行为，重点关注其浊点、表面活性、胶束特性以及对模型疏水性药物卡马西平（CBZ）的增溶能力。通过动态光散射和小角中子散射研究，研究了温度、盐添加和 CBZ 增溶对胶束的影响。TPGS 的浊点为 78°C，具有良好的表面活性（从表面张力降低和吸附参数可以观察到）。通过表面张力和荧光研究获得的临界胶束浓度（CMC）为 0.02 mM。散射研究表明形成了稳定的胶束（平均直径为 12nm），在盐添加（高达 1M NaCl）、CBZ 掺入（高达 5mM）和温度升高（40°C）时，其尺寸没有明显变化。在 5wt%TPGS 中，CBZ 的溶解度提高了约二十倍。考虑到显著的 CBZ 增溶能力及其在核心中的定位，我们建议可以将该制剂用作持续释放载体。