Effect of the combination of ion-pairs strategies and permeation enhancers on iguratimod transdermal patch against rheumatoid arthritis.

Iguratimod (IGU) is a novel anti-rheumatic drug, which has anti-inflammatory effects, inhibits bone destruction, and promotes bone formation. However, the gastrointestinal side-effects caused by oral tablets of IGU pose a challenge. This study aimed to develop an IGU transdermal patch for Rheumatoid Arthritis (RA) through ion-pair and chemical penetrant strategies to improve the therapeutic efficacy. The IGU patch were prepared using IGU-HERP (ion-pair), POCC (permeation promoter), DT 87-4098 (pressure-sensitive adhesive (PSA)), Backings 9720(backing layer), with component ratios optimized through BBD experiments. The resulting formulations increase the IGU loading and skin penetration of the patch. Then the mechanism of permeation promotion of POCC was investigated in terms of drug and skin. The molecular interactions between POCC and IGU ion-pairs were investigated by in vitro artificial membranes, FT-IR, C NMR and molecular simulation experiments. The interaction between POCC and skin stratum corneum was investigated using saturated drug solution permeation assay, exfoliation of stratum corneum assay, ATR-FTIR assay, SEM assay and molecular simulation experiment. The results showed that hydrogen bonding between IGU-HEPR and POCC promoted drug release, while POCC would disrupt the dense structure of the stratum corneum and enhance drug penetration. When IGU-HEPR transdermal patches was applied on the mice model, IGU-HEPR transdermal exhibited good analgesic and anti-inflammatory effect. In conclusion, this study successfully developed an IGU patch against RA, providing a reference for improving the penetration of transdermal patches by using ion-pair strategy.