Mechanistic approach for the development of ultrafine o/w emulsions using blends medium and long chain triglycerides: solubility and bioavailability enhancement of perphenazine

Abstract

A thermodynamically stable ultrafine (o/w) emulsion containing perphenazine for solubility and oral bioavailability enhancement using blends of long and medium chain triglyceride was developed. Formulation was prepared using low energy emulsification phase titration method. The optimized formulations consisted of blend of linseed and sefsol 218 (1:1), polysorbate 40, polyethylene glycol 400 and distilled water as an oil, surfactant, cosurfactant and dispersion phase respectively. The formulations were characterized on the basis of viscosity, refractive index, particle size distribution, spectral transmittance and surface morphology. Formulations were evaluated for release study by everted gut sac using intestinal mucosa. The ex vivo release data showed that nanoemulsions significantly increased the permeation rate of perphenazine over the simple suspension. Following oral administration of nanoemulsion in wistar rats, both AUC and C_max of perphenazine increased by 2.9 fold and 2.54-fold respectively compared with the perphenazine suspension. The resultant bioavailability might be due to increased solubility, bypassing the first-pass metabolism through lymphatic absorption and enhanced permeation potential of perphenazine.