Labrasol® is an efficacious intestinal permeation enhancer across rat intestine: Ex vivo and in vivo rat studies

Labrasol (R) ALF (Labrasol (R)), is a non-ionic surfactant excipient primarily used as a solubilising agent. It was investigated here as an intestinal permeation enhancer in isolated rat colonic mucosae in Ussing chamber and in rat in situ intestinal instillations. Labrasol (R) comprises mono-, di- and triglycerides and mono- and di-fatty acid esters of polyethylene glycol (PEG)-8 and free PEG-8, with caprylic (C-8)- and capric acid (C-10) as the main fatty acids. Source components of Labrasol (R) as well as Labrasol (R) modified with either C-8 or C-10 as the sole fatty acid components were also tested to determine which element of Labrasol (R) was responsible for its permeability-enhancing properties. Labrasol (R) (4, 8 mg/mL) enhanced the transport of the paracellular markers, [C-14] mannitol, FITC-dextran 4000, and FITC-insulin across colonic mucosae. The enhancement was non-damaging, transient, and molecular weight-dependent. The PEG ester fraction of Labrasol (R) also had enhancing properties. When insulin was administered with Labrasol (R) in instillations, it had a relative bioavailability of 7% in jejunum and 12% in colon. C-8- and C-10 versions of Labrasol (R) and the PEG ester fraction also induced similar bioavailability values in jejunal instillations: 6, 5 and 7% respectively. Inhibition of lipases in instillations did not reduce the efficacy of Labrasol (R), suggesting that its mechanism as a PE is not simply due to liberated medium chain fatty acids. Labrasol (R) acts as an efficacious intestinal permeation enhancer and has potential for use in oral formulations of macromolecules and BCS Class III molecules.