The impact of solid and liquid lipids and their lipolysis on griseofulvin bioavailability. In vitro dissolution, in vivo and ex vivo porcine model study

Lipids, either as food components or as drug delivery formulations, are known to enhance the absorption of poorly water-soluble drugs in the gastrointestinal tract. Most research on the effects of different lipids and their lipolysis on dissolution and solubilization of poorly water-soluble drugs is conducted using liquid lipids, including liquid meals. In the present study, we examine the effects of a pure solid lipid, Tristearin (TS), compared to a liquid lipid, Triolein (TO), on the in vitro dissolution and the in vivo bioavailability of the BCS class II drug griseofulvin. Solid hydrophobic drugs may adsorb to solid lipids, and potentially decrease their bioavailability, however, we found that griseofulvin adsorbs negligibly to TS, which undergoes only partial lipolysis and therefore does not seem to contribute to griseofulvin dissolution nor to delay it and therefore TS is not expected to aid or impede griseofulvin bioavailability. Using the swine model to validate this prediction, we observed faster gastric emptying in the fasted state but similar overall bioavailabilities in the fasted and fed states, regardless of meal composition. This prompted an examination of the swine gastrointestinal contents for fed and fasted animals. Similar and high bile acids concentrations were found in fasted and fed states, suggesting a lack of difference in bile levels between the two states which may explain the observed lack of food effect. The use of the swine model to investigate lipid-enhanced bioavailability should be further explored, paying attention to the differences between different swine breeds. The results from in vitro experiments suggest that solid lipids are not expected to affect the bioavailability of BCS class II drugs.