Self-micellizing solid dispersions enhance the properties and therapeutic potential of fenofibrate: Advantages, profiles and mechanisms
作者：Shi NQ, Zhang Y, Li Y, Lai HW, Xiao X, Feng B, Qi XR
關鍵字：Self-micellizing;Fenofibrate;Dissolution/solubility;Hypolipidemic efficacy;Solid dispersions
論文來源：期刊
具體來源：International Journal of Pharmaceutics (IF=3.994)
發表時間：2017年
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.
