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


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.


CONCLUSIONS
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.


CONCLUSIONS
It was feasible for LOXO patch design by combination of ion-pair technology and chemical enhancers.
a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , People's Republic of China.
Mei
M
Hui
a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , People's Republic of China.
Peng
P
Quan
a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , People's Republic of China.
Yingying
Y
Yang
a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , People's Republic of China.
Liang
L
Fang
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D009226:Myristates / Q000737:chemistry*; D010666:Phenylpropionates / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D017550:Spectroscopy, Fourier Transform Infrared; D057968:Transdermal Patch
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009226:Myristates; D010666:Phenylpropionates; C008205:isopropyl myristate; C040656:loxoprofen
Drug-in-adhesive patch; organic amine; pharmacodynamics; preformulation; transdermal drug delivery