Influence of Polymer Hydrophobicity on Transdermal Drug Absorption

ABSTRACT Transdermal drug delivery systems (TDDS) rely on carefully engineered polymer matrices and adhesives to meter drug flux across the stratum corneum (SC) while maintaining patch adhesion, comfort, and stability. Polymer hydrophobicity—captured by solubility parameters, water contact angle, and partition behavior—plays a central role in drug loading, solid–state form, thermodynamic activity, interfacial partitioning into the skin, and overall permeation. This review synthesizes fundamental skin‐transport theory with polymer science to explain how the hydrophobicity of pressure‐sensitive adhesives (PSAs), rate‐controlling membranes, and backing/liners governs transdermal performance. We unify classic barrier models and recent mechanistic data to (i) map polymer hydrophobicity to drug distribution (polymer↔SC), (ii) highlight formulation levers (tackifiers, plasticizers, ionic liquid cosolvents) that tune microenvironment polarity without compromising adhesion, (iii) compare acrylic, silicone, and polyisobutylene (PIB) systems for lipophilic vs hydrophilic drugs, (iv) discuss in vitro/in vivo correlations (IVIVC) and QSPR/PBPK frameworks that include polymer descriptors, and (v) outline regulatory, quality, and manufacturability implications.