Pestieau Aude, Krier Fabrice, Lebrun Pierre, Brouwers Adeline, Streel Bruno, Evrard Brigitte
Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, C.I.R.M., University of Liège, CHU, Tour 4, 2nd floor, 4000 Liège, Belgium.
Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, C.I.R.M., University of Liège, CHU, Tour 4, 2nd floor, 4000 Liège, Belgium.
Int J Pharm. 2015 May 15;485(1-2):295-305. doi: 10.1016/j.ijpharm.2015.03.027. Epub 2015 Mar 18.
The aim of this study was to develop a formulation containing fenofibrate and Gelucire(®) 50/13 (Gattefossé, France) in order to improve the oral bioavailability of the drug. Particles from gas saturated solutions (PGSS) process was chosen for investigation as a manufacturing process for producing a solid dispersion. The PGSS process was optimized according to the in vitro drug dissolution profile obtained using a biphasic dissolution test. Using a design of experiments approach, the effects of nine experimental parameters were investigated using a PGSS apparatus provided by Separex(®) (Champigneulles, France). Within the chosen experimental conditions, the screening results showed that the drug loading level, the autoclave temperature and pressure, the connection temperature and the nozzle diameter had a significant influence on the dissolution profile of fenofibrate. During the optimization step, the three most relevant parameters were optimized using a central composite design, while other factors remained fixed. In this way, we were able to identify the optimal production conditions that would deliver the highest level of fenofibrate in the organic phase at the end of the dissolution test. The closeness between the measured and the predicted optimal dissolution profiles in the organic phase demonstrated the validity of the statistical analyses.
本研究的目的是开发一种含有非诺贝特和Gelucire(®) 50/13（法国加蒂福斯公司）的制剂，以提高该药物的口服生物利用度。选择气体饱和溶液法制备颗粒（PGSS）工艺作为制备固体分散体的生产工艺进行研究。根据使用双相溶出试验获得的体外药物溶出曲线对PGSS工艺进行了优化。采用实验设计方法，使用法国尚皮尼厄勒的Separex(®)公司提供的PGSS装置研究了九个实验参数的影响。在所选实验条件下，筛选结果表明药物载量、高压釜温度和压力、连接温度以及喷嘴直径对非诺贝特的溶出曲线有显著影响。在优化步骤中，使用中心复合设计对三个最相关的参数进行了优化，而其他因素保持不变。通过这种方式，我们能够确定在溶出试验结束时能在有机相中提供最高水平非诺贝特的最佳生产条件。有机相中测量的和预测的最佳溶出曲线之间的接近程度证明了统计分析的有效性。
