INFLUENCE OF LIPOLYSIS ON DRUG ABSORPTION FROM THE GASTROINTESTINAL-TRACT

Bioavailability of hydrophobic drugs from the gastro-intestinal (GI) t ract can be enhanced by formulation in digestible oils. This form of d elivery is an effective way of avoiding the slow dissolution step whic h limits availability from solid dosage forms. Essentially the drug re mains in solution during its passage and prior to absorption. Digestio n of the oily components of the formulation will have a major influenc e 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 so lubility of hydrophobic drugs in the presence of such micelles is grea tly enhanced. This has the effect of dispersing the drug extremely fin ely and allows rapid partitioning of the drug into the aqueous continu um for absorption. However, formulation of oils with surfactants may i nhibit lipolysis, which suggests that formulation should include an in vitro assessment of the lipolysis of the delivery system. Here we rev iew the solubilization of drugs in bile salt micelles, describe method s which can be used for assessment of lipolysis in vitro, and present preliminary biostudies using formulations optimised for rapid lipolysi s. There is a need for more systematic studies on the influence of lip olysis on absorption from the GI tract, but current data suggest that optimisation of lipolysis will be an important strategy in formulation of oily systems.