In vitro–in vivo correlation for consolidation of permeation parameters using different membranes in Franz Cell with a transdermal rivastigmine patch

The permeation and release of transdermal drug delivery systems can be evaluated through in vitro Franz Cells performance assays. These can use different types of synthetic and natural membranes to make bioavailability predictions of transdermal formulations using in vitro – in vivo correlation (IVIVC) models. However, the methodology is not currently standardized, and this is required urgently. The aim of this work is to standardize membranes for the permeability assay of transdermal formulations through a conventional methodology using Franz Cells. It also aims to develop IVIVC models for the prediction of transdermal rivastigmine pharmacokinetic profiles. The permeation assay of a commercial formulation was conducted using natural membranes (human, pig, and rat skin) and synthetic membrane (Strat-M®). Formulation permeation profiles were similar among rat skin and Strat-M®, but showed significant differences compared to pig and human skin, which were also different from each other. The in silico pharmacokinetic model of rivastigmine was able to accurately simulate systemic drug disposition and can be considered the first to be developed for transdermal rivastigmine. The IVIVC models were established in GastroPlus™ followed by a convolution step, and the highest correlation coefficient was observed for human skin, followed by porcine skin, Strat-M®, and finally rat skin. This difference between the permeation profiles of the membranes may be attributed to the arrangement and thickness of their skin compartments. This study will contribute to the standardization of membrane use in transdermal permeation testing, as well as in the development of reliable in silico models for predicting transdermal bioavailability. • Standardization of membranes for studies on Franz Cells is urgently required. • Permeation profile of Exelon®Patch was discriminated between different membranes. • The developed in silico model simulated the systemic disposition of rivastigmine. • The in vitro–in vivo correlation was established followed by a convolution step. • Human skin is the standard for permeation; pig ear skin is a suitable alternative.