塞来昔布凝胶透皮促渗剂的配方研究

Study on the formulation of penetration enhancers in Celecoxib Gels

目的评价不同配方的透皮促渗剂对塞来昔布凝胶剂中塞来昔布皮肤渗透性的影响,为优化塞来昔布凝胶剂配方提供实验依据。方法以卡波姆为凝胶基质,按照析因设计的原则,选用4种不同配方的透皮促渗剂制备凝胶剂;采用改良Franz扩散池,以HPLC法测定塞来昔布凝胶剂中塞来昔布在12h内的累积渗透量(Q),并计算其稳态流量(J)和渗透系数(Kp)。结果 4个实验组中塞来昔布在12h内的累积渗透量(Q)分别为12.24,11.76,14.13和12.39μg·cm-2,其中以薄荷醇5g·kg^(-1)和氮酮20g·kg-1为配方时Q值最大,达14.13μg·cm^(-2);塞来昔布的渗透过程符合Higuchi方程,稳态流量(J)及渗透系数(Kp)高于其他3个实验组。结论以卡波姆为凝胶基质时,薄荷醇和氮酮联用作透皮促渗剂对塞来昔布透皮特性有协同增效作用,两者最佳配方为薄荷醇和氮酮分别为5和20g·kg^(-1)。

Objective To provide experimental evidence for the optimizing formulation of Celecoxib Gels by studying the effects of different doses of penetration enhancers on the penetration of celecoxib through skin in vitro . Methods With carbopol as the gel base,the factorial design method was used to choose the optimal formulation of penetration enhancers among 4 different formulations to prepare Celecoxib Gels.The release rate of celecoxib in the release media was detected by modified Franz diffusion cells method,and the steady percutaneous speed （ J ）,permeability coefficient （K p） and the accumulative permeation quantity （ Q ） in 12 h were calculated. Results The accumulative permeation quantity （ Q ） in 12 h of celecoxib from the Celecoxib Gels made with the 4 different tests were 12.24,11.76,14.13 and 12.39 μg·cm -2 ,respectively.The gel with 5 g·kg -1 menthol and 20 g·kg -1 azone as penetration enhancers had the maximum Q value,14.13 μg·cm -2 ,its penetration process conformed to Higuchi equation,and the steady percutaneous speed （ J ） and permeability coefficient （ K p）were also higher than the other 3 experimental groups. Conclusion With carbopol as the gel base,menthol and azone have a synergistic effect on the percutaneous penetration of Celecoxib Gels,and the optimalformulation is 5 g·kg -1 menthol and 20 g·kg -1 azone.