Enhanced oral absorption of halofantrine enantiomers after encapsulation in a proliposomal formulation.

ABSTRACT

In this study, we evaluated the ability of a coated, encapsulated formulation to increase the oral bioavailability of (+/-)-halofantrine (HF) enantiomers, a drug with low and erratic oral bioavailability. After encapsulation of HF in distearoylphosphatidylcholine, the dried particles were coated with cellulose acetate phthalate. A suspension of the product was made using methylcellulose as a dispersion agent, and the product was administered to Sprague-Dawley rats to provide a HF dose of 7 mg kg-1 as the HCl salt. HF HCl powder in 1% methylcellulose with or without liposomal product excipients was also administered to separate groups of rats, which served as control groups. Serial blood samples were obtained from the rats and plasma was assayed by stereospecific high-performance liquid chromatography. There were no significant differences in the area under the concentration-time curve (AUC) or maximum concentration (Cmax) between the two control groups. Plasma concentrations of both HF enantiomers were significantly higher in the rats given HF as an encapsulated proliposomal formulation compared with the control groups. Compared with methylcellulose control, the encapsulation product resulted in increases of 41 to 47% in the AUC of HF enantiomers, and 90 to 100% in Cmax. The ability of an encapsulated proliposomal product to significantly increase the oral absorption of HF was clearly demonstrated.