Abstract

Purpose

2-(10,11-Dihydro-10-oxodibenzo [b,f] thiepin-2-yl) propionic acid (Zaltoprofen) is classified as a BCS class II anti-inflammatory drug, having low solubility and less bioavailability.

Methods

This study describes the development and characterization of self-micro emulsifying drug delivery system (SMEDDS) of the poorly water-soluble compound Zaltoprofen that resulted in improved aqueous solubility, dissolution, and in-vivo oral absorption. The solubility of Zaltoprofen was determined in various vehicles, including oils, surfactants, and co-surfactants. Pseudo-ternary phase diagrams were constructed to identify the most efficient self-emulsification region. The optimized SMEDDS used for Zaltoprofen formulations contained 80% mixtures of surfactant:co-surfactant Labrasol:Cremophor RH 40 (4:1), and 20% of oil, ethyl oleate. Further, SMEDDS was characterized by particle size, zeta potential, dissolution studies, and anti-inflammatory activity.

Results

The Zaltoprofen-SMEDDS rapidly formed fine oil-in-water microemulsion, which was thermodynamically stable, having an average particle size of 451.3 ± 3.2 nm. The in-vitro dissolution rate of Zaltoprofen from SMEDDS was significantly higher (p<.01) compared to marketed tablets in 0.1N HCL and pH 4.5 buffer. SMEDDS showed highly significant inhibition (p<.01) of inflammation in rat paw edema compared to the drug.

Conclusions

The study demonstrated that the self-micro emulsifying system poses a promising strategy for developing hydrophobic compounds with low oral bioavailability.

中文翻译：

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扎托洛芬自微乳化给药系统的配方、表征和体内评价

摘要

目的

2-(10,11-Dihydro-10-oxodibenzo [b,f] thiepin-2-yl) propionic acid (Zaltoprofen) 属于 BCS II 类抗炎药，溶解度低，生物利用度低。

方法

本研究描述了水溶性差的化合物扎托洛芬的自微乳化药物递送系统 (SMEDDS) 的开发和表征，该系统可改善水溶性、溶出度和体内口服吸收。Zaltoprofen 在各种载体中的溶解度，包括油、表面活性剂和助表面活性剂。构建伪三元相图以确定最有效的自乳化区域。用于扎托洛芬配方的优化 SMEDDS 包含 80% 的表面活性剂：助表面活性剂 Labrasol:Cremophor RH 40 (4:1) 和 20% 的油、油酸乙酯的混合物。此外，SMEDDS 的特征在于粒径、zeta 电位、溶出度研究和抗炎活性。

结果

Zaltoprofen-SMEDDS 迅速形成细小的水包油微乳液，其热力学稳定，平均粒径为 451.3 ± 3.2 nm。与市售片剂在 0.1N HCL 和 pH 4.5 缓冲液中相比， SMEDDS 中扎托洛芬的体外溶出率显着更高 ( p <.01)。与药物相比， SMEDDS 显示出对大鼠爪水肿炎症的显着抑制 ( p <.01)。

结论

该研究表明，自微乳化系统为开发具有低口服生物利用度的疏水性化合物提供了一种有前景的策略。