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 FENdissolution/solubility profiles was conducted to understand the enhanced therapeuticpotential. SmSD and NsSD of FEN systems (SmSD/FEN and NsSD/FEN) were fabricatedusing a fuse-quench cooling method. The self-micellizing Soluplus® cloudpoint was then determined experimentally and FEN phase solubility was measuredin 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 amorphousstate 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-densitylipoprotein (HDL). Compared with non-self-micellizing polymers,self-micellizing Soluplus® significantly inhibited FEN crystalgrowth from a supersaturated state. However, no obvious difference inintermolecular 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.
