Particle Size Distribution Affects the Human Bioavailability of Phenytoin

概要

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The particle size distributions of two commercially available batches of phenytoin (PHT) crystals were determined. Fifty-four percent of PHT crystals of one of the batches was in a large particle size range of 177-350 μm, while the other batch had a rather average particle size distribution in the range of 74-350 μm. Dissolution of the batches was tested in the JPX distintegration test medium No. 1 (pH 1.2)with 0.2% Tween 80. The apparent dissolution rate of the batch of smaller particle size was about 1.9 times faster than that of the batch of larger particle size for initial dissolution up to 30 min, but thereafter the rates became almost the same. This is because smaller particles of PHT dissolved within 30 min and dissolution thereafter was due to the larger particles in the batches. A cross-over clinical study was conducted to compare the bioavailability of these batches in humans. The area under the blood concentration-time curve (AUC) for the batch of smaller particle size was about 2.6 times that of the batch of larger particle size.The present results indicate that differences in particle size distribution' of PHT can cause significant differences in dissolution characteristics, especially at the initial stage of dissolution, and substantial differences in bioavailability.
公益社団法人日本薬学会の論文
1986-10-25