Shi Nian-Qiu, Zhang Yong, Li Yan, Lai Hong-Wei, Xiao Xiao, Feng Bo, Qi Xian-Rong
School of Pharmacy, Jilin Medical University, Jilin132013, Jilin Province, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China.
College of Life Science, Jilin University, 2699 Qianjin Street, Changchun 130012, Jilin Province, China.
Int J Pharm. 2017 Aug 7;528(1-2):563-577. doi: 10.1016/j.ijpharm.2017.06.017. Epub 2017 Jun 7.
The goal of this work was to compare fenofibrate (FEN)-containing self-micellizing solid dispersion (SmSD) and non-self-micellizing solid dispersion (NsSD) systems. Exploration of underlying mechanisms to improve FEN dissolution/solubility profiles was conducted to understand the enhanced therapeutic potential. SmSD and NsSD of FEN systems (SmSD/FEN and NsSD/FEN) were fabricated using a fuse-quench cooling method. The self-micellizing Soluplus cloud point was then determined experimentally and FEN phase solubility was measured in solutions containing self-micellizing Soluplus or non-self-micellizing polymers. Physicochemical characteristics of SmSD/FEN and NsSD/FEN were evaluated using microscopic morphology, amorphous state, thermal performance, dissolution and solubility profiles. FEN exhibited an amorphous state in SmSD/FEN but was not completely amorphous in NsSD/FEN. The dissolution and solubility profile of SmSD/FEN achieved about 1.2- to 2-fold improvement over that of NsSD/FEN. Consequently, relatively enhanced hypolipidemic efficacy in vivo was observed in SmSD/FEN vs NsSD/FEN, as measured by serum levels of total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Compared with non-self-micellizing polymers, self-micellizing Soluplus significantly inhibited FEN crystal growth from a supersaturated state. However, no obvious difference in intermolecular interactions was observed between SmSD/FEN and NsSD/FEN systems. Overall, the SmSD approach exhibited as trengthened dissolution effect, enhancing FEN hyperlipidemic disease therapy efficacy.
这项工作的目标是比较含非诺贝特（FEN）的自微乳化固体分散体（SmSD）和非自微乳化固体分散体（NsSD）系统。对改善FEN溶解/溶解度曲线的潜在机制进行了探索，以了解增强的治疗潜力。采用熔融骤冷法制备了FEN系统的SmSD和NsSD（SmSD/FEN和NsSD/FEN）。然后通过实验确定自微乳化辅料Soluplus的浊点，并在含有自微乳化辅料Soluplus或非自微乳化聚合物的溶液中测量FEN的相溶解度。使用微观形态、非晶态、热性能、溶解和溶解度曲线对SmSD/FEN和NsSD/FEN的物理化学特性进行了评估。FEN在SmSD/FEN中呈现非晶态，但在NsSD/FEN中并非完全非晶态。SmSD/FEN的溶解和溶解度曲线比NsSD/FEN提高了约1.2至2倍。因此，通过总胆固醇（TC）、总甘油三酯（TG）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）的血清水平测量，观察到SmSD/FEN在体内的降血脂功效相对于NsSD/FEN有所增强。与非自微乳化聚合物相比，自微乳化辅料Soluplus显著抑制了FEN从过饱和状态的晶体生长。然而，在SmSD/FEN和NsSD/FEN系统之间未观察到分子间相互作用的明显差异。总体而言，SmSD方法表现出增强的溶解效果，提高了FEN治疗高脂血症疾病的疗效。
