Molecular mechanism of high capacity-high release transdermal drug delivery patch with carboxyl acrylate polymer: Roles of ion-ion repulsion and hydrogen bond.

In this study, a high capacity-high release transdermal patch was conducted with COOH polyacrylate polymer (PA-1) and non-steroidal anti-inflammatory drugs (NSAIDs), which were characterized using miscibility study, in vitro drug release, drug skin absorption studies in vitro and in vivo. And ibuprofen with the highest cargo loading capacity was chosen as a model drug to investigate innovative molecular mechanism, which was proposed based on ion-ion repulsion and hydrogen bond by FT-IR, Raman, 13C NMR and X-ray photoelectron spectroscopy (XPS). Drug loading and skin absorption in PA-1 was improved up to 2.4 and 2.5 times, respectively. The hydrogen bond formed between drug (COOH) and PA-1 (COOH) was weaken by repulsive interaction using FT-IR and Raman spectra, and molecular mobility of PA-1 was elevated by dielectric spectroscopy. And COO- was confirmed as molecular basis of repulsion in PA-1 through new peak appearance (α-carbon of COOH: 77.22 ppm) of 13C NMR and 9% increased carbonyl content in XPS spectra. It was further confirmed by enhanced conductivity of PA-1 with dielectric spectroscopy, EPR spectra, four-point probe method and molecular modeling by appearance of COO-. In conclusion, our results revealed that ion-ion repulsion decreased hydrogen bonding to construct a high capacity-high release patch.