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

Abstract

Iguratimod (IGU) is a novel anti-rheumatic drug that 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 was 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 the drug and skin. The molecular interactions between POCC and IGU ion-pairs were investigated by ex vitro artificial membranes, FT-IR, ¹³C 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 were applied to the rat model, IGU-HEPR transdermal patches exhibited good analgesic and anti-inflammatory effects. In conclusion, this study successfully developed an IGU patch for local administration against RA, providing a reference for improving the penetration of transdermal patches by using an ion-pair strategy.