Lidocaine Transdermal Patch: Pharmacokinetic Modeling and In Vitro–In Vivo Correlation (IVIVC)

Abstract

The present study aims to develop the correlation between in vitro and in vivo skin permeation of lidocaine in its transdermal patch. In order to minimize the run-to-run variability during in vitro skin permeation studies, release normalized cumulative percent (%Ctn) was calculated. A suitable polynomial mathematical model was used to establish a correlation between time and %Ctn. Percent in vivo absorbed was calculated by using numerical deconvolution (NDC) and non-compartmental analysis (NCA) methods. Pharmacokinetic (PK) parameters such as AUClast and Cmax were predicted with the established in vitro–in vivo correlation (IVIVC) models. The minimum prediction errors in NDC method for Cmax were found to be −30.9 and −25.4% for studies I (in vivo study in human volunteers with one batch of Lidoderm patch; internal validation) and II (in vivo study in human volunteers with another batch of Lidoderm patch; external validation), respectively, whereas minimum prediction errors in NCA method were relatively low (3.9 and 0.03% for studies I and II, respectively) compared to those in NDC method. The prediction errors for AUClast were found to be less than 2% for both methods and studies. The established method in this study could be a potential approach for predicting the bioavailability and/or bioequivalence for transdermal drug delivery systems.