Drug solubilization behavior during in vitro digestion of simple triglyceride lipid solution formulations

Purpose. The purpose of this study was to characterize the solubilization and precipitation characteristics of a range of poorly watersoluble drugs during digestion of either long-chain or medium-chain triglyceride (TG) lipid formulations. Methods. TG solution formulations of five selected drugs ( griseofulvin, diazepam, danazol, cinnarizine, and halofantrine) were digested in vitro and drug distribution/solubilization behavior in the resulting digests assessed. Results. For the less lipophilic drugs, the mass of drug dissolved in either medium or long-chain TG was low and the drugs partitioned rapidly into the aqueous digestion phase. For the higher log P drugs, drug transfer to the aqueous phase was limited by accumulation in undigested long-chain TG. In contrast, medium-chain TG was digested completely producing a dispersed aqueous phase that was capable, at least in the case of the high log P drugs, of supporting supersaturated drug concentrations. Conclusions. The solubilization behavior of lipophilic drugs on digestion of simple TG lipid formulations is a function of the lipophilicity of the drug ( which dictates the drug dose and the partitioning behavior), the nature of the colloidal phases produced on digestion of the different formulation lipids, and the kinetics of drug transfer between the digesting formulation and the colloidal phases produced.