Laboratory for Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Belgium.
Eur J Pharm Sci. 2009 Dec 8;38(5):479-88. doi: 10.1016/j.ejps.2009.09.012. Epub 2009 Sep 24.
In order to gain a better understanding of the reasons of successful self-microemulsifying drug delivery systems (SMEDDS) formulation, ten poorly water-soluble drugs, exhibiting different physicochemical properties, were selected. The solubility of the compounds was determined in various oils (long and medium chain) and surfactants (HLB>12 and HLB<10). The best performing excipients were selected for SMEDDS formulation. The droplet size and zeta potential of SMEDDS were measured in the absence and the presence of drug. Media, time and the presence of drug showed little or no influence on droplet size of most systems. Some systems displayed a different zeta potential in the presence of drugs. In vitro pharmaceutical performance of the SMEDDS formulations was investigated using the dialysis bag method in reverse mode next to conventional in vitro release methodology. The results suggested that the measured concentration of the compounds inside the dialysis bag corresponded to solubility of the compound in the release medium, which suggested that the formation of micelles inside the dialysis bag was delayed or disturbed. Conventional in vitro release methodology with pH change from acidic to neutral appeared as a simple method which gives valuable information about the dispersion and the solubilization ability of the SMEDDS formulation at different pHs. In general, formulate-ability in SMEDDS was found to depend on the solubility of the drugs in the excipients and log P of the compounds (the optimal log P was found between 2 and 4).
为了更好地理解成功的自微乳药物传递系统 (SMEDDS) 制剂的原因，选择了十种具有不同物理化学性质的疏水性差的药物。在各种油 (长链和中链) 和表面活性剂 (HLB>12 和 HLB<10) 中测定了化合物的溶解度。选择最佳性能的赋形剂用于 SMEDDS 制剂。在有无药物的情况下测量 SMEDDS 的粒径和zeta 电位。介质、时间和药物的存在对大多数系统的粒径几乎没有或没有影响。一些系统在存在药物时显示出不同的 zeta 电位。通过反向透析袋法在体外研究了 SMEDDS 制剂的药物性能，同时还进行了常规的体外释放方法学研究。结果表明，透析袋内化合物的测量浓度与释放介质中化合物的溶解度相对应，这表明在透析袋内形成胶束的过程被延迟或干扰。从酸性到中性的 pH 值变化的常规体外释放方法学似乎是一种简单的方法，它可以在不同 pH 值下提供有关 SMEDDS 制剂分散和增溶能力的有价值信息。一般来说，SMEDDS 的制剂可加工性取决于药物在赋形剂中的溶解度和化合物的 log P (发现最佳 log P 在 2 到 4 之间)。
