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

• Published in: International journal of pharmaceutics 2023-09, Vol.644, p.123302-123302, Article 123302
• Main Authors: Wang, Liuyang, Pang, Yu, Zheng, Qi, Ruan, Jiuheng, Fang, Liang, liu, Chao
• Format: Article
• Language: English
• Subjects: Ion-pair; Mabuterol; Molecular interaction; Stability; Transdermal patch
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2023.123302

[Display omitted] 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 Fabs = 75.27%. The increased TGA (213.11 °C), disproportionation energy (ΔG = 97.44 KJ), and ion-pair lifetime (Tlife = 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.