Comparative Study of Rotigotine Release and Permeation from the Neupro® Transdermal Patch: An In Vitro-In Vivo Correlation

Rotigotine (RTG) is a non-ergolinic dopaminergic agonist indicated for Parkinson’s and Willis-Ekbom diseases, administered exclusively via Neupro® transdermal patch. Given the therapeutic relevance and physicochemical challenges of RTG, this study aimed to characterize its transdermal delivery profile by employing USP dissolution testing and Franz diffusion cells as complementary methodologies for evaluating drug release and skin permeation, and to establish an in vitro–in vivo correlation (IVIVC) based on retrospective correlation between in vitro release/permeation data and previously reported in vivo pharmacokinetic data. In vitro release tests were conducted using USP Apparatus 5 and 6 under varying agitation speeds and media compositions, while permeation studies employed Franz diffusion cells with synthetic membranes and pig ear skin. RTG quantification was performed using HPLC–DAD. An IVIVC was established using the Wagner–Nelson deconvolution method based on previously published pharmacokinetic data. USP Apparatus 5 at 75 rpm in pH 6.0 phosphate buffer showed most discriminative release performance, while in vitro permeation data using pig ear skin exhibited strong retrospective correlation with in vivo fraction absorbed data (R2 = 0.9819). Synthetic membranes allowed full RTG release but failed to replicate skin barrier function. Kinetic modeling revealed Higuchi behavior for release and zero-order kinetics for permeation through natural skin. The developed methods effectively differentiated between modified and reference patches, confirming their applicability for quality control and post-registration changes. Additionally, the results highlight the role of in vitro models in predicting in vivo performance of the RTG transdermal system, contributing to formulations optimization/development and guiding regulatory decisions in bioequivalence studies.