Roles of molecular interaction and mobility on loading capacity and release rate of drug-ionic liquid in long-acting controlled release transdermal patch

This study aimed to develop long-acting controlled release transdermal patches containing ionic liquids (ILs) of weak acid drugs and investigate effects of pressure sensitive adhesives (PSAs) on drug-ILs loading and release. Here, ketoprofen, flurbiprofen and loxoprofen were chosen as model drugs, and triethylamine was selected as model counterion. Three types of PSAs containing carboxyl (PSA-COOH), hydroxyl (PSA-OH) and non-functional group (PSA-none) were respectively synthesized. Microscopy results showed that the solubility of drug-ILs in PSA-COOH was enhanced up to 4.50 times compared with that in other PSAs. Drug release results showed that the average release percentage of drug-ILs in PSA-COOH (70.97%) had no significant difference with that in PSA-OH (73.22%) and PSA-none (73.47%). While drug skin penetration performances demonstrated that the average skin flux of drug-ILs in PSA-COOH (23.73 μg/(cm 2 h)) was much higher than that in PSA-OH (6.75 μg/(cm 2 h)) and PSA-none (4.32 μg/(cm 2 h)). As illustrated by FTIR, Raman and DSC analysis, ionic hydrogen bonding determined drug-ILs loadings, and interaction strength between drug-ILs and PSA-COOH was the strongest owing to the deprotonated PSA-COO – . Rheology study revealed that decreased storage modulus and increased phase shift angle of PSA-COOH determined drug-ILs release owing to strong plasticization at high drug-ILs loading. Remarkably, the long-acting controlled release patches were successfully developed and molecular mechanisms were revealed.