Formulation and in-vitro and in-vivo testing of a phenytoin self-emulsifying drug delivery system (SEDDS)

The goals of our research are to develop and characterize a self-emulsifying drug delivery system (SEDDS) of phenytoin, and to evaluate its relative bioavailability in rats. Hydrophobic drugs can often be dissolved in SEDDS allowing them to be encapsulated as unit dosage forms for oral administration. SEDDS will disperse to form a fine emulsion in the gut so that the drug remains in solution avoiding the dissolution step, which frequently limits the rate of absorption of hydrophobic drugs.;Phenytoin was formulated as SEDDS in hard gelatin capsules. The optimized SEDDS formulation was compared in-vitro to DilantinRTM suspension and chewable tablets using dissolution method and zeta potential. The optimized SEDDS formulation was also compared in-vivo to DilantinRTM suspension. Rats were used as the animal model. In all studies HPLC was used to analyze phenytoin concentrations.;Phenytoin optimized SEDDS formulation showed good in-vitro emulsification characteristics, high zeta potential, and in-vitro release of phenytoin higher than 80% in different dissolution media. The optimized SEDDS formulation showed significantly higher and faster in-vitro release of phenytoin compared to DilantinRTM suspension and chewable tablets. In-vivo studies showed that Both C30 minutes, and AUC-10min-10h of phenytoin after SEDDS administration were significantly higher than after DilantinRTM suspension administration when both formulations were given orally to rats.;Phenytoin was successfully formulated as a SEDDS. The new formulation showed significantly higher in-vitro release of phenytoin to the aqueous media in both simulated gastric and intestinal fluids when compared to both Dilantin RTM suspension and chewable tablets.;The in-vivo study showed that the SEDDS formulation exhibited different absorption behavior from the commercially available suspension (Dilantin RTM). The most significant effect of the SEDDS formulation was the sustained release of phenytoin.