Gastrointestinal lipolysis of lipid-based excipients intended for the oral drug delivery of poorly water-soluble drugs

Labrasol®and Gelucire®44/14 are lipid-based excipients used for the oral drug delivery of poorly water-soluble drugs. These macrogolglycerides are composed of acylglycerols and PEG esters, potential substrates of digestive lipases. We developed an in vitro method to simulate the gastrointestinal lipolysis of these excipients and to evaluate the impact of lipolysis in vivo. At the end of the gastric phase, the composition of both excipients was significantly modified underlining the importance of gastric lipolysis in vivo. We also studied the influence of excipients’ lipolysis on the solubilization of a poorly water-soluble drug, cinnarizine, in aqueous phase. Gastrointestinal lipolysis of Labrasol®was a prerequisite to maintain cinnarizine in aqueous solution, whereas the lipolysis of Gelucire®44/14 did not affect the cinnarizine solubilization.