Effect of O-acylterpineol derivatives on transdermal delivery of meloxicam

LI Yan; ZHAO Li-gang; WANG Chun-yan; ZHENG Li-na; WANG Hui-li

Abstract：Objective:To develop O-acylterpineol derivative as transdermal penetration enhancers for meloxican (MLXC),including 2-(4-methylcyclohex-3-en-l-yl) propan-2-yl butanoate (T-BUT),2-(4-methylcyclohex-3-en-l-yl) propan-2-yl hexanoate (T-HEX),2-(4-methylcyclohex-3-en-l-yl) propan-2-yl heptanoate (T-HEP),2-(4-methylcyclohex-3-en-l-yl) propan-2-yl decanoate (T-DEC),2-(4-methylcyclohex-3-en-l-yl) propan-2-yl dodecanoate (T-DOD),2-(4-methylcyclohex-3-en-l-yl) propan-2-yl tetradecanoate (T-TET),2-(4-methylcyclohex-3-en-l-yl)propan-2-yl stearate (T-STE) and (E)-2-(4-methylcyclohex-3-en-l-yl) propan-2-yl octadec-9-enoate (T-OA).Methods:The compounds were synthesized by using α-terpineol and fatty acid.The in vitro permeation studies of MLXC were conducted in isopropyl myristate(IPM) solution or from patches in side-by-side diffusion cells,and the enhancing effects of O-acylterpineol,l-menthol,azone and N-methylpyrrolidone(NMP) on the permeation behavior of MLXC were also investigated.Results:The results of in vitro permeation experiment showed that the compounds including 5 ％ terpineol,5 ％ T-BUT,5％ T-HEX,5 ％ T-HEP,5 ％ menthol and 5 ％ NMP had significant enhancing effects on the penetration of MLXC compared with the control(P ＜ 0.05),additionally,NMP and T-HEX had higher penetration activity than terpineol(P ＜ 0.05).While in the DIA patches only α-terpineol,menthol,T-HEX and NMP could promote the penetration of MLXC.The combination of 5％ NMP and 5％ T-HEX could provide the largest penetration amount of MLXC within 8 h (5.08-fold) compared with the control group (P ＜ 0.05).Conclusion:O-acylterpineol derivatives have significant promoting effects on the penetration of MLXC,which indicates that O-acylterpineol might be a promising enhancer.