Separation and characterization of the colloidal phases produced on digestion of common formulation lipids and assessment of their impact on the apparent solubility of selected poorly water-soluble drugs

Colloidal mixtures containing bile salts (BS), phosphatidylcholine (PC), and medium and long-chain monoglycerides and fatty acids were prepared as model systems to represent typical intestinal contents after digestion of formulation derived lipids under both low (5 mM BS/1.25 mM PC) and high (20 mM BS/5 mM PC) BS and PC conditions. Size-exclusion chromatography of the colloidal species that formed in the medium-chain digests indicated the presence of vesicles, mixed micelles, and simple micelles, whereas the long-chain digests contained only vesicles and mixed micelles. In the long-chain digests the mixed micellar phase was the predominant drug solubilizing species for griseofulvin, danazol, and halofantrine, although for increasingly lipophilic drugs, the vesicular phase contributed an increasing proportion of the solubilization capacity. In contrast, the solubilization capacity of the vesicular phase was predominant in the medium-chain digests, and no clear trends were evident in the relationship between drug lipophilicity and proportional solubilization. These data highlight the need to consider the colloidal species that form in the small intestine during the digestion of common formulation lipids and the coincident enhancement in drug solubilization provided under these circumstances. (C) 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:634-648, 2003.