Mechanistic approach for the development of ultrafine oil-water emulsions using monoglyceride and blends of medium and long chain triglycerides: enhancement of the solubility and bioavailability of Perphenazine

Abstract

A kinetically stable ultra-fine oil-water (o/w) emulsion containing Perphenazine and blends of long and medium chain triglycerides was prepared. The purpose of the ultra-fine emulsion was to increase the oral bioavailability of Perphenazine. The formulations were prepared using a low energy emulsification phase titration method. The optimized formulations consisted of blends of linseed oil and Sefsol 218 (1:1) (oil phase), polysorbate 40 (surfactant), polyethylene glycol 400 (cosurfactant) and distilled water (dispersion medium). Characterization of viscosity, refractive index, particle size distribution, spectral transmittance and surface morphology of the formulations was performed. The release rate of Perphenazine from the formulations was quantified using the everted gut sac of rat intestinal mucosa. The ex vivo release data demonstrated that the formulated nanoemulsions increased significantly the permeation rate of Perphenazine when compared with a suspension. Following oral administration of selected nanoemulsions in Wistar rats, the AUC and Cmax of Perphenazine increased by 2.9 and 2.54-fold respectively compared with the Perphenazine suspension. The observed increase in bioavailability may be due to the increase in the dissolution rate from the molecularly dissolved drug in the oil phase and an increased rate of dispersion of the drug in the gastrointestinal (GI) tract which leads to greater absorption into the blood