Clinical studies with oral lipid based formulations of poorly soluble compounds

Dimitrios G Fatouros¹, Ditte M Karpf¹, Flemming S Nielsen¹, Anette Mullertz¹

Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark; ¹Contributed equally to this work

Abstract: This work is an attempt to give an overview of the clinical data available on lipid based formulations. Lipid and surfactant based formulations are recognized as a feasible approach to improve bioavailability of poorly soluble compounds. However not many clinical studies have been published so far. Several drug products intended for oral administration have been marketed utilizing lipid and surfactant based formulations. Sandimmune^® and Sandimmune Neoral^® (cyclosporin A, Novartis), Norvir^® (ritonavir), and Fortovase^® (saquinavir) have been formulated in self-emulsifying drug delivery systems (SEDDS). This review summarizes published pharmacokinetic studies of orally administered lipid based formulations of poorly aqueous soluble drugs in human subjects. Special attention has been paid to the physicochemical characteristics of the formulations, when available and the impact of these properties on the in vivo performance of the formulation. Equally important is the effect of concurrent food intake on the bioavailability of poorly soluble compounds. The effect of food on the bioavailability of compounds formulated in lipid and surfactant based formulations is also reviewed.

Keywords: lipid formulations, poorly soluble compounds, pharmacokinetics, human clinical studies, lipophilic compounds, SEDDS, emulsions, food effect