Properties of rapidly dissolving eutectic mixtures of poly(ethylene glycol) and fenofibrate: The eutectic microstructure

Poly(ethylene glycol) or PEG is an ideal inactive component for preparing simple binary eutectic mixtures because of its low entropy of fusion (similar to0.0076 J/mol-K), lower melting point (similar to62degreesC) compared to most pharmaceuticals, miscibility with drugs at elevated temperatures, and its covalent crystalline lattice. Implication of these physicochemical properties on eutectic crystallization and size reduction of the drug is discussed. Enhancement of the dissolution rate of a poorly soluble compound through the formation of PEG-drug eutectics was investigated using fenofibrate. Solid dispersions of PEG-fenofibrate when characterized, revealed that PEG and fenofibrate form a simple eutectic mixture containing 20-25%(w/w) fenofibrate at the eutectic point. Eutectic crystallization led to the formation of an irregular microstructure in which fenofibrate crystals were found to be less than 10 pm in size. Dissolution rate improvement of fenofibrate correlated with the phase diagram, and the amount of fenofibrate released from the dispersions that contained fenofibrate as a eutectic mixture was at least10-fold higher compared to untreated fenofibrate. On aging, the dissolution rate of the dispersion containing 15%(w/w) fenofibrate in PEG remained unaltered. The results indicate that PEG-drug eutectic formation is a valuable option for particle size reduction and subsequent dissolution rate improvement. (C) 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:505-515, 2003.