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