Elucidating the release and permeation mechanisms of emulsion-type cataplasms from a structural perspective

Drug release and permeation play crucial roles in the therapeutic efficacy of cataplasms. However, due to the lack of research on the mechanisms underlying drug release and permeation, achieving optimal release and permeation characteristics through trial-and-error methods is inefficient. Therefore, we aimed to investigate the mechanisms of drug release and permeation in emulsion-type cataplasms from a structural perspective.Cataplasms with varied crosslinking densities, drug loadings, and drug types were prepared; drug release and permeation studies were performed using Franz diffusion cells, while the microstructural evolution of both the cataplasms and the skin was characterized via scanning electron microscopy, differential scanning calorimetry, Fourier-transform infrared spectroscopy, and histology.It was revealed that drug release essentially occurred as the drug escaped from structural constraints through the swelling of the crosslinked network. Drug permeation was demonstrated to be governed by four synergistic mechanisms: (1) the physical contact established by the intimate adhesion between cataplasms and the skin; (2) the influence of drug release amount on drug permeation behavior; (3) stratum corneum hydration induced by water-mediated keratin swelling; (4) disruption of the stratum corneum lipid structure resulting from L-menthol. In addition, this study revealed that the acidity and basicity of the drug itself constituted a key determinant of drug permeation. Overall, the present work is expected to provide a scientific basis for the rational design of cataplasms, improve research and development efficiency, and further promote advances in this field.