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 ( approximately 0.0076 J/mol-K), lower melting point (approximately 62 degrees C) 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 microm 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 least 10-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.
Law
Devalina
D
Pharmaceutical and Analytical Research and Development, Global Pharmaceutical Research and Development, Abbott Laboratories, R4P3, AP9, 100 Abbott Park Road, Abbott Park, IL 60064, USA. devalina.law@abbott.com
Wang
Weili
W
Schmitt
Eric A
EA
Qiu
Yihong
Y
Krill
Steven L
SL
Fort
James J
JJ
D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D011345:Fenofibrate / Q000737:chemistry* / Q000493:pharmacokinetics; D008863:Microspheres; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility
D004337:Drug Carriers; D011092:Polyethylene Glycols; D011345:Fenofibrate