Cho Young-Dae, Park Young-Joon
Pharmaceutical Research Institute CJ Cheiljedang, 522-1, Deokpyeong-ri, Majang-myeong, Gyeonggi-do, Icheon-si, Korea.
Arch Pharm Res. 2014 Feb;37(2):193-203. doi: 10.1007/s12272-013-0169-4. Epub 2013 Jun 11.
Fenofibrate is indicated in hypercholesterolemia and hypertriglyceridemia alone or combined (types IIa, IIb, III, IV, and V dyslipidemias). However, due to its low solubility in water, it has low bioavailability after oral administration. In order to improve the dissolution rate, fenofibrate was formulated into a self-microemulsifying drug delivery system (SMEDDS). We used pseudoternary phase diagrams to evaluate the area of microemulsification, and an in vitro dissolution test was used to investigate the dissolution rate of fenofibrate. The optimized formulation for in vitro dissolution and bioavailability assessment consisted of propylene glycol laurate (Lauroglycol FCC) (60 %), macrogol-15-hydroxystearate (Solutol HS 15) (27 %), and diethylene glycol monoethyl ether (Transcutol-P) (13 %). The mean droplet size of the oil phase in the microemulsion formed by the SMEDDS was 131.1 nm. The dissolution rate of fenofibrate from SMEDDS was significantly higher than that of the reference tablet. In vivo pharmacokinetics study of fenofibrate in beagles administered SMEDDS-A form resulted in a 3.7-fold increase in bioavailability as compared with the reference drug. Our studies suggested that the fenofibrate containing SMEDDS composition can effectively increase the solubility and oral bioavailability of poorly water-soluble drugs.
非诺贝特适用于单纯性高胆固醇血症和高甘油三酯血症或两者合并存在的情况（IIa、IIb、III、IV和V型血脂异常）。然而，由于其在水中的溶解度较低，口服给药后的生物利用度也较低。为了提高溶出速率，非诺贝特被制成了自微乳化药物递送系统（SMEDDS）。我们使用伪三元相图来评估微乳化区域，并采用体外溶出试验来研究非诺贝特的溶出速率。用于体外溶出和生物利用度评估的优化配方由月桂酸丙二醇酯（Lauroglycol FCC）（60%）、聚乙二醇15 - 羟基硬脂酸酯（Solutol HS 15）（27%）和二乙二醇单乙醚（Transcutol - P）（13%）组成。由SMEDDS形成的微乳液中油相的平均液滴尺寸为131.1 nm。非诺贝特从SMEDDS中的溶出速率显著高于参比片剂。在给予SMEDDS - A剂型的比格犬体内进行的非诺贝特药代动力学研究表明，与参比药物相比，生物利用度提高了3.7倍。我们的研究表明，含有SMEDDS组合物的非诺贝特可有效提高难溶性药物的溶解度和口服生物利用度。
