Preparation and In Vitro /In Vivo Study of Phenytoinum Natricum Drug-Resin Sustained-Release Suspension

In the present study, sustained-release suspensions with strong base anion exchange resin as carrier were prepared. Complexes of ion-exchange resins and Phenytoin Natricum (PN), a model drug, were prepared using the batch method. The physicochemical characteristics of the drug-resin complex were studied. The SEM results showed that there was no drug crystallization on the surface of drug resinates. The DSC and XRD studies proved that the drug was in amorphous nature. The sustained-release resin microcapsules of PN were prepared with emulsion-solvent evaporation method. The effects of different factors including formulation process and technique on the release behavior of sustained-release microcapsules were investigated, and the optimum formulation was selected by orthogonal experimental design method. The sustained-release suspension was formulated with xanthan gum as suspending agent. Sedimentation volume and re-dispersibility of the prepared suspension were found to be satisfactory. The release behavior of the PN sustained-release suspensions in vivo and in vitro was investigated. The cumulative release rates of 0.5, 1, and 2 h were 45, 60 and 70%, respectively, in vitro, according to the release requirements in the United States Pharmacopoeia on sustained release capsules. The in vivo pharmacokinetics was studied in male rats. The marketed PN tablets used as reference, the in vivo pharmacokinetics test showed that the suspension and reference had no significant differences in AUC0-24h, but indicated a significant difference in tmax and C-max. The tmax increased from 4 h (reference) to 6 h (test), The C-max reduced from 24.97 mu g/mL(reference) to 16.22 mu g/mL (test), indicating a sustained release property in vivo. The average relative bioavailability of reformulated sustained release suspension was 95.04% compared to PN tablets with decreased C-max, delayed tmax and had an obviously sustained-release effect.