Patel Ashok R, Vavia Pradeep R
Centre for Novel Drug Delivery Systems, Department of Pharmaceutical Sciences, University Institute of Chemical Technology, Matunga, Mumbai, India.
AAPS J. 2007 Oct 26;9(3):E344-52. doi: 10.1208/aapsj0903041.
The present work was aimed at formulating a SMEDDS (self-microemulsifying drug delivery system) of fenofibrate and evaluating its in vitro and in vivo potential. The solubility of fenofibrate was determined in various vehicles. Pseudoternary phase diagrams were used to evaluate the microemulsification existence area, and the release rate of fenofibrate was investigated using an in vitro dissolution test. SMEDDS formulations were tested for microemulsifying properties, and the resultant microemulsions were evaluated for clarity, precipitation, and particle size distribution. Formulation development and screening was done based on results obtained from phase diagrams and characteristics of resultant microemulsions. The optimized formulation for in vitro dissolution and pharmacodynamic studies was composed of Labrafac CM10 (31.5%), Tween 80 (47.3%), and polyethylene glycol 400 (12.7%). The SMEDDS formulation showed complete release in 15 minutes as compared with the plain drug, which showed a limited dissolution rate. Comparative pharmacodynamic evaluation was investigated in terms of lipid-lowering efficacy, using a Triton-induced hypercholesterolemia model in rats. The SMEDDS formulation significantly reduced serum lipid levels in phases I and II of the Triton test, as compared with plain fenofibrate. The optimized formulation was then subjected to stability studies as per International Conference on Harmonization (ICH) guidelines and was found to be stable over 12 months. Thus, the study confirmed that the SMEDDS formulation can be used as a possible alternative to traditional oral formulations of fenofibrate to improve its bioavailability.
本研究旨在制备非诺贝特的自微乳化药物递送系统（SMEDDS），并评估其体外和体内潜力。测定了非诺贝特在各种载体中的溶解度。使用伪三元相图评估微乳化存在区域，并通过体外溶出试验研究非诺贝特的释放速率。对SMEDDS制剂进行微乳化性能测试，并对所得微乳液的澄清度、沉淀和粒径分布进行评估。根据相图结果和所得微乳液的特性进行制剂开发和筛选。用于体外溶出和药效学研究的优化制剂由Labrafac CM10（31.5%）、吐温80（47.3%）和聚乙二醇400（12.7%）组成。与溶出速率有限的普通药物相比，SMEDDS制剂在15分钟内完全释放。使用 Triton 诱导的大鼠高胆固醇血症模型，从降脂疗效方面进行了比较药效学评估。与普通非诺贝特相比，SMEDDS制剂在Triton试验的I期和II期显著降低了血清脂质水平。然后根据国际协调会议（ICH）指南对优化后的制剂进行稳定性研究，发现其在12个月内稳定。因此，该研究证实SMEDDS制剂可作为非诺贝特传统口服制剂的一种可能替代物，以提高其生物利用度。
