Preparation and evaluation of fenofibra te-gelucire 44/14 solid dispersions

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Date
2007
Authors
al-Dhalli, Samer
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Abstract
The potential of solid dispersion-based formulation using Gelucire 44/14 as a carrier to enhance the dissolution and oral bioavailability of fenofibrate, a poorly water-soluble drug, was investigated. Solid dispersions with different drug-tocarrier ratios were prepared by the conventional fusion method and characterized using thermal analysis, optical microscopy and dissolution testing. The dissolution results were compared with those of two fenofibrate formulations; the micronized drug powder and commercial tablet having suprabioavailability. No substantial increase in the drug dissolution, over that of micronized fenofibrate, could be obtained from prepared solid dispersions. Decreased drug dissolution was attributed to the presence of large drug crystals formed during the preparation of the solid dispersions. However, modifying the preparation conditions, by adding the drug to the carrier at a relatively low temperature, and incorporating polyethylene glycol (PEG) 400 to lower the melting point of the matrix, resulted in much smaller drug crystals and rapidly eroding matrices being obtained. Consequently, complete drug dissolution was achieved after approximately 60 minutes of the test, compared with 65% dissolution for micronized drug powder. In vivo evaluation of fenofibrate-Gelucire 44114 solid dispersion containing polyethylene glycol (PEG) 400 showed that the extent of drug absorption, expressed as AUCo-oo, was increased by approximately 60% over that of micronized fenofibrate. On the basis of the results of this study, it was concluded that when the conventional fusion method fails to reduce the drug particle size, the technique of incorporating drug microparticles into the matrix at lower temperatures is worth considering. The findings also suggest that lowering the melting point of the matrix can increase the dissolution rate.
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Keywords
Fenofibra te-gelucire , Solid Dispersions
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