R&D Center, Kuhnil Pharm Co., Ltd., Seoul, 153-787, Korea.
Arch Pharm Res. 2010 Sep;33(9):1375-87. doi: 10.1007/s12272-010-0911-0. Epub 2010 Oct 9.
A new triglyceride-free propofol microemulsion for intravenous injection was formulated using nonionic surfactants, poloxamers and polyethylene glycol 660 hydroxystearate. The aim of this investigation was to evaluate the formulation for storage stability, antimicrobial activity, toxicity and preclinical efficacy. The results were compared to the characteristics obtained for the most commonly used formulation of propofol (Diprivan®). The mean particle diameter of the microemulsion was less than 100 nm so that it could be readily sterilized using a 0.22 μm membrane at room temperature. The microemulsion formulation demonstrated enhanced stability compared to the marketed macroemulsion formulation. In a stress storage condition, it was physicochemically stable for at least 40 months. This new formulation showed higher antimicrobial activity, lower risk of hyperlipidemia and better tolerability than Diprivan®. In preclinical studies, the efficacy and pharmacokinetic profile of the microemulsion were similar to those of Diprivan®. Nevertheless, the administration of the microemulsion caused considerably low histamine release compared to the macroemulsion. Based on these results, the newly developed microemulsion of propofol appeared to have several advantages and, thus, could be an alternative to the fat macroemulsions of propofol.
一种新型无甘油三酯丙泊酚微乳注射液，由非离子表面活性剂、泊洛沙姆和聚乙二醇 660 羟硬脂酸酯组成。本研究旨在评估该制剂的储存稳定性、抗菌活性、毒性和临床前疗效。并将结果与丙泊酚最常用的制剂（得普利麻）的特性进行比较。该微乳的平均粒径小于 100nm，因此可以在室温下使用 0.22μm 膜进行无菌过滤。与市售的大乳剂相比，该微乳制剂具有更好的稳定性。在应激储存条件下，至少 40 个月内其理化性质稳定。与得普利麻相比，这种新配方具有更高的抗菌活性、更低的高脂血症风险和更好的耐受性。在临床前研究中，微乳的疗效和药代动力学特征与得普利麻相似。然而，与大乳剂相比，微乳的组胺释放量明显较低。基于这些结果，新开发的丙泊酚微乳似乎具有许多优势，因此可能成为丙泊酚脂肪乳的替代品。
