Lipid-based formulations: exploring the link between in vitro supersaturation and in vivo exposure

Lipid based drug delivery systems (LBDDS) hold great promise as vehicles to enhance the bioavailability of drugs where low aqueous solubility provides a barrier to effective exposure after oral administration. Unlike traditional solid formulations, LBDDS typically present drugs to the gastrointestinal tract (GIT) in solution, albeit in non-aqueous solution, and the challenge to the formulator is to identify approaches that maintain drug in a solubilized form throughout GI transit. Within the GIT, however, LDBBS are diluted and digested – conditions which typically reduce solublization capacity and promote drug precipitation. Inherent in this process is a period of supersaturation prior to drug precipitation. Approaches to kinetically stabilize this supersaturated state provide a viable approach to the generation of more robust formulations. Here we address the conditions under which the processing of lipid based formulations is most likely to lead to supersaturation, the factors that impact on the attainment of a supersaturated state, the conditions under which polymeric excipients are most likely to aid in supersaturation stabilization and finally the link between in vitro supersaturation and in vivo exposure.