Mei Hui1, Peng Quan1, Yingying Yang1, Liang Fang1. 1. a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , People's Republic of China.
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/cm(2)/h. In patch, the highest flux of 369.37 ± 34.32 µg/cm(2)/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/cm(2)/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.
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 arthritisrat 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/cm(2)/h. In patch, the highest flux of 369.37 ± 34.32 µg/cm(2)/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/cm(2)/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.
Entities:
Keywords:
Drug-in-adhesive patch; organic amine; pharmacodynamics; preformulation; transdermal drug delivery
Authors: Elisabeth D Chang; Christer Hogstrand; Thomas H Miller; Stewart F Owen; Nic R Bury Journal: Environ Sci Technol Date: 2019-01-15 Impact factor: 9.028