Factors affecting the bioavailability of phenytoin

Abstract

The bioavailability of seven phenytoin (DPH) formulations, five brands of tablets and two suspensions, was measured in a cross-over study with six healthy volunteers. Single doses of 600 mg of DPH were used and the bioavailability was determined as the area under the serum DPH concentration-time curve (AUC). Highly significant differences between the bioavailability of various products were found. The highest bioavailability was obtained with suspension prepared from the micronized raw material of DPH and the lowest bioavailability (26% of that of the former suspension) with the tablets having the largest particle size of DPH. The in vitro dissolution rate of the products in borate buffer at pH 9 showed a significant (p less than 0.01; r=0.93) correlation with the in vivo bioavailability of the DPH products. In addition to the particle size, several other formulation factors are important for dissolution rate and absorption characteristics of DPH products. The properly performed measurement of the in vitro dissolution rate can be used as a preliminary screening test in predicting the bioavailability of DPH products.