The effect of ion-pair formation combined with penetration enhancers on the skin permeation of loxoprofen

Abstract

Context: Loxoprofen (LOXO) is a non-steroidal anti-inflammatory drug. Repeated oral administrations induce gastrointestinal side effects. Patches are a promising alternative. Objective: The aim of this study was to investigate the effects of organic amines on the skin permeation of LOXO and finally design a patch with a comparable permeation profile and pharmacodynamic effects to the commercial LOXONA® plaster. Materials and methods: The effects of organic amines were assessed by flux values of LOXO from isopropyl myristate (IPM), using horizontal diffusion cell and rabbit skin. FTIR spectroscopy was used to confirm ion-pair formation. Anti-inflammatory and analgesic activity assessments were performed in the adjuvant arthritis rat model and acetic acid-induced writhing syndrome in mouse, separately. Results and discussion: Results showed that triethylamine (TEA) was the most potential candidate in IPM, with the highest flux of 499.75 ± 32.40 µg/cm2/h. In patch, the highest flux of 369.37 ± 34.32 µg/cm2/h was still obtained by LOXO–TEA. Combined with penetration enhancers, the cumulative amounts were further increased in presence of 5% IPM, which exhibited a flux of 840.04 ± 66.38 µg/cm2/h as two times of the commercial one. Ultimately, anti-inflammatory and analgesic activity assessment presented that a comparable pharmacodynamic activity with the commercial one could be obtained by the patch we designed. Additionally, we also found that LOXO patch applied topically exerted a systemic effect, and the effect was dose-dependent. Conclusion: It was feasible for LOXO patch design by combination of ion-pair technology and chemical enhancers.