Formulation design and bioavailability assessment of lipidic self-emulsifying formulations of halofantrine

The potential for lipidic self-emulsifying drug delivery systems (SEDDS) and self-microemulsifying drug delivery systems (SMEDDS) to improve the oral bioavailability of a poorly absorbed, antimalarial drug (Halofantrine, Hf) was investigated in fasted beagles. Hf free base, rather than the commercially available hydrochloride salt (Hf.HCl), was studied due to its much higher solubility in lipidic triglyceride solvents. The multi-component delivery systems were optimised by evaluating their ability to self-emulsify when introduced to an aqueous medium under gentle agitation, and by determination of particle size of the resulting emulsion. Optimised formulations selected for bioavailability assessment were medium-chain triglyceride SEDDS and SMEDDS, and a long-chain triglyceride SMEDDS. The relevant pharmacokinetic parameters of Hf, and its desbutyl metabolite, were determined relative to an intravenous formulation. The lipid-based formulations of Hf base afforded a six- to eight-fold improvement in absolute oral bioavailability relative to previous data of the solid Hf.HCl tablet formulation. These data indicate the utility of dispersed lipid-based formulations for the oral delivery of Hf free base, and potentially other lipophilic drugs. (C) 1998 Elsevier Science B.V. All rights reserved.