Development of mabuterol transdermal patch: Molecular mechanism study of ion-pair improving patch stability

This paper aimed to prepare a Mabuterol (MAB) patch for treating asthma by ion-pair strategy to overcome the drug's thermal instability and elucidate the molecular mechanisms of the stabilization effect. The formulation factor, including counter-ion and pressure-sensitive adhesive (PSA), was optimized by the stability and in vitro skin permeation studies. The molecular mechanism of ion-pair stability was characterized using TGA, Raman, FT-IR, NMR, XPS, and molecular modeling. The optimized patch comprised MAB-Lactic acid (MAB-LA) and hydroxyl adhesive (AAOH) as the matrix, with Q = 126.47 ± 9.75 μg/cm² and F_abs = 75.27%. The increased TGA (213.11 °C), disproportionation energy (ΔG = 97.44 KJ), and ion-pair lifetime (T_life = 2.21 × 10³) indicated that the counter-ion improved MAB stability through strong ionic and hydrogen bonds with LA. The remaining drug content in the MAB-LA patch was 15% higher than that of the pure MAB patch after storage for 12 months at room temperature, which was visualized by Raman imaging. The interaction between MAB-LA and AAOH PSA via hydrogen bond decreased the diffusion rate and increased the drug stability further. This study successfully developed the MAB patch, which provided a reference for applying ion-pairing strategies to improve the stability of transdermal patches.