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 (%Ct n) was calculated. A suitable polynomial mathematical model was used to establish a correlation between time and %Ct n. Percent in vivo absorbed was calculated by using numerical deconvolution (NDC) and non-compartmental analysis (NCA) methods. Pharmacokinetic (PK) parameters such as AUC last and C max were predicted with the established in vitro-in vivo correlation (IVIVC) models. The minimum prediction errors in NDC method for C max 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 AUC last 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.
Keywords: IVIVC; bioequivalence; lidocaine; numerical deconvolution; transdermal.