Multimodal in vitro characterization techniques for assessing the adhesion of transdermal patches: A proof-of-concept study

Abstract

Adhesion is a critical factor in determining the quality, efficacy, and safety of transdermal patches. The adhesive properties directly influence drug permeation and flux, especially for matrix system patches. For potent therapeutics, the strength of adhesion and any minor tampering during wear can significantly impact the patch’s in vivo performance. Adhesive properties can vary over time due to changes in polymer interactions, with storage-induced three-dimensional alterations potentially affecting both adhesive strength and drug characteristics. Despite these complexities, no standardized method currently exists for measuring adhesive strength in transdermal patches. Therefore, reliable and consistent testing methods are essential to ensure patch quality and therapeutic efficacy. This study presents a multimodal approach to assess the adhesion of transdermal patches, incorporating traditional probe-tack and in vitro permeation tests, along with innovative techniques such as interferometry for surface topography analysis and infrared thermography to evaluate structural and adhesive deficiencies. The feasibility of these methods was validated by tampering fresh and expired patches across multiple rounds (2R, 5R, 10R). Validation was confirmed by measuring patch thickness before and after tampering with digital calipers, quantifying removed drug, and analyzing patch roughness and topography via interferometry. Adhesive performance was further assessed using the probe-tack test, while nicotine permeation profiles (both intact and tampered) were evaluated using vertical Franz diffusion cells. Statistical analysis, including one-way ANOVA and Tukey’s post-hoc test, identified significant differences between the datasets. The study utilized two different brands of 14 mg nicotine patches as models. Results indicated that the reference patches exhibited superior adhesive performance and uniform distribution compared to the test patches. The data demonstrates the potential of thermal imaging and interferometry as complementary techniques to distinguish adhesive performance differences in Q2-equivalent transdermal patches produced by different manufacturers.