School of Pharmaceutical Sciences, Hebei University, Baoding 071002, China.
Int J Pharm. 2011 Nov 28;420(2):251-5. doi: 10.1016/j.ijpharm.2011.08.043. Epub 2011 Sep 3.
The objective of the present study was to formulate a microemulsion system for oral administration to improve the solubility and bioavailability of fenofibrate. Various formulations were prepared using different ratios of oils, surfactants and co-surfactants (S&CoS). Pseudo-ternary phase diagrams were constructed to evaluate the microemulsification existence area. The formulations were characterized by solubility of the drug in the vehicles, mean droplet size, and drug content. The stability was also investigated by store for 3 months under 4°C, 25°C and 40°C and diluted 100 times for 3 days. The optimal formulation consists of 25% Capryol 90, 27.75% Cremophore EL, 9.25% Transcutol P and 38% water (w/w), with a maximum solubility of fenofibrate up to ∼40.96 mg/mL. The microemulsion was physicochemical stable and mean droplet size was about 32.5-41.7 nm. The pharmacokinetic study was performed in dogs and compared with Lipanthy capsule. The result showed that microemulsion has significantly increased the C(max) and AUC compared to that of Lipanthy capsule (p<0.05). The oral bioavailability of fenofibrate microemulsions (FEN-MEs) in ME-3 and ME-4 were 1.63 and 1.30-fold higher than that of the capsule. Our results indicated that the microemulsions could be used as an effective formulation for enhancing the oral bioavailability of fenofibrate.
本研究的目的是制备一种口服微乳系统，以提高非诺贝特的溶解度和生物利用度。使用不同比例的油、表面活性剂和助表面活性剂（S&CoS）制备了各种制剂。构建了伪三元相图来评估微乳存在区域。通过测定药物在载体中的溶解度、平均粒径和药物含量来表征制剂。还通过在 4°C、25°C 和 40°C 下储存 3 个月以及稀释 100 倍 3 天来考察稳定性。最佳制剂由 25%Capryol 90、27.75%Cremophor EL、9.25%Transcutol P 和 38%水（w/w）组成，非诺贝特的最大溶解度高达约 40.96mg/mL。微乳是物理化学稳定的，平均粒径约为 32.5-41.7nm。在狗体内进行了药代动力学研究，并与 Lipanthy 胶囊进行了比较。结果表明，与 Lipanthy 胶囊相比，微乳显著增加了 C(max)和 AUC（p<0.05）。ME-3 和 ME-4 中非诺贝特微乳的口服生物利用度分别比胶囊高 1.63 倍和 1.30 倍。我们的结果表明，微乳可以作为一种有效的制剂，用于提高非诺贝特的口服生物利用度。
