Simultaneous lipolysis/permeation in vitro model, for the estimation of bioavailability of lipid based drug delivery systems

The simultaneous processes of lipid digestion and absorption together determine the oral bioavailability of drugs incorporated into lipid based drug delivery systems (LBDDS). A number of slightly different protocols for in vitro lipolysis are widely accepted; however, the permeation process has so far not been included into the models due to the harsh conditions of lipid digestion compromising permeation barriers. The present study for the first time combines biomimetic permeation and lipolysis of LBDDS. The focus of the current work was on the functional stability of the barrier - Permeapad (R) during lipid digestion. Using calcein as a marker molecule the investigations demonstrated that the barrier was able to maintain its permeation properties in the presence of the SNEDDS (self-emulsifying drug delivery system) formulation, the lipolysis medium, and the lipolysis medium while digesting the SNEDDS. Furthermore, the permeation of cinnarizine (CINN) from SNEDDS was demonstrated to be lower, if the formulation as such was applied as compared to the digested formulation. This support the general perception that meaningful in vitro evaluation of lipid based formulations requires consideration of both, the digestion and absorption, i.e. lipolysis and permeation. (C) 2017 Published by Elsevier B.V.