Gastrointestinal absorption of phenytoin from an oil-in-water microemulsion

Abstract

The absorption profile of phenytoin Na emulsion were examined compared to that of phenytoin suspension after oral administration in the rat. The corn oil-in-water emulsion, particle size of 184±57.8 nm, was prepared using a microfludizer, and phenytoin Na added by shaft homogenizer. The phenytoin emulsion or suspension, 100 mg/kg, were intubated intragastrically using oral dosing needle and blood samples were withdrawn via an indwelling cannula from the conscious rat. Plasma concentrations of phenytoin were measured with HPLC using phenacetin as an internal standard. The plasma concentration versus time data were fitted to a one compartment open model and the pharmacokinetic parameters were calculated using the computer program, Boomer. The phenytoin plasma concentrations from the emulsion at each observed time were about 1.5–2 times higher than those from the suspension, significantly at time of 5, 6 and 7 hr after administration. The absorption (k_a) and elimination rate constant (k_e) were not altered significantly, however the AUC increased from 65.6 to 106.7 μg·hr/ml after phenytoin suspension or emulsion oral administration, respectively. From an equilibrium dialysis study, the diffusion rate constant (k_IE) was considerably higher from the phenytoin Na emulsion (0.0439 hr⁻¹) than phenytoin suspension (0.0014 hr⁻¹).