Application of high-polarity hydroxyl polyacrylate pressure sensitive adhesive in rizatriptan transdermal drug...

This study aimed to design a rizatriptan (RIZ) transdermal patch by combining of high-polarity hydroxyl pressure sensitive adhesive (PSA) AAOH-45 with an ion-pair strategy and investigate the molecular mechanism of high content hydroxyl PSA to enhance drug-PSA miscibility. RIZ free base, ion-pair complexes and PSAs containing hydroxyl group were prepared and characterized. Formulation factors including counter-ions, PSAs, drug-loading and others were optimized through single-factor studies and evaluated through pharmacokinetic studies and skin irritation tests. The properties of high polarity PSA and molecular mechanism of drug-PSA miscibility were investigated through molecular simulation, FTIR spectra, ¹³C NMR spectra, DSC, and rheology study. The optimized formulation contained 20 % (w/w) RIZ-OA (Rizatriptan-Oleic acid), 80 % AAOH-45 (w/w) as the matrix, and had a thickness of 90 μm. Compared with the oral group (MRT_0-t = 5.96 ± 0.97 h) and the control patch group (MRT_0-t = 11.30 ± 1.78 h), the pharmacokinetic behavior of the optimization group demonstrated sustained drug delivery behavior (MRT_0-t = 20.21 ± 0.61 h) with no irritation phenomenon. The miscibility of RIZ with PSAs was positively correlated with the mass percentage of 2-HEA. Higher polar similarity, lower flowability, and stronger intermolecular interaction were responsible for the higher compatibility of high hydroxyl PSA with the drug. This study provided a reference for increasing the drug-loading in PSA and developing RIZ patch.