School of Pharmacy, The University of Auckland, Auckland, New Zealand.
Int J Pharm. 2012 Jul 15;431(1-2):130-7. doi: 10.1016/j.ijpharm.2012.04.020. Epub 2012 Apr 23.
This study is the first to investigate and demonstrate the potential of microemulsions (MEs) for sustained release parenteral drug delivery, due to phase transition behavior in aqueous environments. Phase diagrams were constructed with Miglyol 812N oil and a blend of (co)surfactants Solutol HS 15 and Span 80 with ethanol. Liquid crystal (LC) and coarse emulsion (CE) regions were found adjacent to the ME region in the water-rich corner of the phase diagram. Two formulations were selected, a LC-forming ME and a CE-forming ME and each were investigated with respect to their rheology, particle size, drug release profiles and particularly, the phase transition behavior. The spreadability in an aqueous environment was determined and release profiles from MEs were generated with gamma-scintigraphy. The CE-forming ME dispersed readily in an aqueous environment, whereas the LC-forming ME remained in a contracted region possibly due to the transition of ME to LC at the water/ME interface. Gamma-scintigraphy showed that the LC-forming ME had minimal spreadability and a slow release of (99m)Tc in the first-order manner, suggesting phase conversion at the interface. In conclusion, owing to the potential of phase transition, LC-forming MEs could be used as extravascular injectable drug delivery vehicles for prolonged drug release.
这项研究首次通过水相中的相转变行为，研究并证明了微乳液（MEs）在经肠胃外给药的缓释中的潜力。利用 Miglyol 812N 油和（共）表面活性剂 Solutol HS 15 和 Span 80 与乙醇构建了相图。在相图的水相富区，发现了与 ME 区相邻的液晶（LC）区和粗乳液（CE）区。选择了两种配方，一种是形成 LC 的 ME，另一种是形成 CE 的 ME，并分别对其流变学、粒径、药物释放曲线进行了研究，特别是相转变行为。在水相中的铺展性进行了测定，并通过γ闪烁照相法生成了 ME 的释放曲线。CE 形成的 ME 很容易在水相环境中分散，而 LC 形成的 ME 可能由于 ME 在水/ME 界面处向 LC 的转变而保持在收缩区。γ闪烁照相法表明 LC 形成的 ME 的铺展性最小，并且（99m）Tc 以一级方式缓慢释放，表明界面处发生了相转变。总之，由于相转变的潜力，LC 形成的 ME 可用作延长药物释放的血管外注射药物递送载体。
