Mechanistic Insights Underlying the Drug Release and Skin Permeation of Guanfacine Transdermal Patch with Various Acrylic Pressure-Sensitive Adhesives

Acrylic pressure-sensitive adhesives (PSAs) are widely applied in transdermal drug delivery systems (TDDS). However, the molecular mechanisms underlying the effect of functional groups of PSAs on drug release and transdermal permeation properties remain insufficiently clear. In this study, we investigated the effect of acrylic PSAs' functional groups on the in vitro release and transdermal permeation properties of a model drug guanfacine (GFC). The rates of release and permeation were hydroxyl PSA (PSA-OH) > non-functional group PSA (PSA-None) > carboxyl PSA (PSA-COOH). Thermal analysis, molecular modeling, Raman spectroscopy, and FTIR were employed to characterize the drug-PSA interactions. The strength of the interaction force between GFC and PSA-None was determined to be negligible. The primary amino of GFC formed a medium-strength hydrogen bond with the hydroxyl of PSA-OH and a strong ionic interaction with the carboxyl of PSA-COOH. Compared to PSA-None, PSA-OH featured a weaker mechanical strength, a higher rheological phase shift angle (δ), and a lower glass transition temperature (T_g), resulting in improved molecular mobility. Furthermore, PSA-OH exhibited higher tack, viscosity, and polarity, providing superior skin adhesion. Overall, it has been demonstrated that drug release and permeation were determined by a combination of interaction strength, molecular mobility, and skin adhesion. The novel discovery expands our understanding of the molecular mechanism of drug-PSA-skin interactions, offering a crucial point of reference for the development‌ of GFC transdermal patches.