In vitro and in vivo availability of hydrophilized phenytoin from capsules.

The effect of phenytoin hydrophilization on the liquid penetration rate into prepared plugs, on the disintegration time, on the in vitro release rate, and on in vivo absorption in humans was studied. Hydrophilization was performed by intensive mixing of the hydrophobic drug with a small amount of methylcellulose solution. Liquid penetration into the treated plugs was independent of the liquid wetting potency and extremely high compared to the pure drug plugs. Analogous results were obtained for the disintegration time and in vitro release rates from capsules loaded with pure and treated drug. A bioavailability study in seven healthy volunteers showed immediate absorption of the treated drug but a 1-hr absorption lag time for the pure drug.