Influence of lipolysis on drug absorption from the gastro-intestinal tract

Bioavailability of hydrophobic drugs from the gastro-intestinal (GI) tract can be enhanced by formulation in digestible oils. This form of delivery is an effective way of avoiding the slow dissolution step which limits availability from solid dosage forms. Essentially the drug remains in solution during its passage and prior to absorption. Digestion of the oily components of the formulation will have a major influence on the fate of the drug in the gut. In many cases digestion will be advantageous in that the drug may be solubilized within mixed micelles of bile components and the products of triglyceride lipolysis. The solubility of hydrophobic drugs in the presence of such micelles is greatly enhanced. This has the effect of dispersing the drug extremely finely and allows rapid partitioning of the drug into the aqueous continuum for absorption. However, formulation of oils with surfactants may inhibit lipolysis, which suggests that formulation should include an in vitro assessment of the lipolysis of the delivery system. Here we review the solubilization of drugs in bile salt micelles, describe methods which can be used for assessment of lipolysis in vitro, and present preliminary biostudies using formulations optimised for rapid lipolysis. There is a need for more systematic studies on the influence of lipolysis on absorption from the GI tract, but current data suggest that optimisation of lipolysis will be an important strategy in formulation of oily systems.