运用裂区设计寻找塞来昔布凝胶最佳配方  

Application of split-plot experiment design in screening celecoxib gels

作　　者：熊静悦[1] 朱九群[2] 艾佳晨 曾明辉[3] 谭正怀[1] 

机构地区：[1]四川省中医药科学院,四川成都610041 [2]四川省人民医院,四川成都610072 [3]邛崃市医疗中心医院,四川邛崃611530

出　　处：《中国医院药学杂志》2017年第21期2117-2121,共5页Chinese Journal of Hospital Pharmacy

基　　金：四川省中医药管理局科研课题(编号:2010-G-093);四川省卫生厅科研基金资助项目(编号:090437)

摘　　要：目的:寻找塞来昔布(celecoxib,CLX)凝胶的最佳配方。方法:采用三裂式裂区设计,主区为羟丙基甲基纤维素、海藻酸钠及卡波姆3种基质,副处理为透皮剂月桂氮芯卓酮(氮酮)的两种水平(1.0%和2.0%),亚副处理为透皮剂薄荷醇的两种水平(0.5%和1.0%),重复3次实验。运用改良的Franz扩散池,选用不同配方塞来昔布制剂作促渗性试验,采用HPLC法测定和计算药物12 h累积释放量(Q)。结果:裂区分析发现区组之间并无显著差异,但各种基质之间存在显著差异;透皮剂氮酮及薄荷醇均对CLX透过皮肤起着非常重要的促进作用,氮酮、薄荷醇均与基质存在显著的协同交互作用;薄荷醇与氮酮之间,以及薄荷醇、基质和氮酮三者之间均存在显著的协同交互作用。进一步的析因设计的方差分析发现在以羟丙基甲基纤维素为基质的凝胶中,氮酮在促进CLX透过皮肤的过程中发挥主要作用;薄荷醇则对CLX透过皮肤无明显作用,但氮酮与薄荷醇合用对CLX透过皮肤表现出显著的协同增效作用。在海藻酸钠为基质的凝胶中,氮酮、薄荷醇均可显著促进CLX透过皮肤;两者合用,对CLX透过皮肤表现出显著的协同增效作用。在以卡波姆为基质的凝胶中,氮酮以及薄荷醇均无显著促进CLX透过皮肤的作用;氮酮与薄荷醇合用也无显著的协同或拮抗作用。结论:本研究结果提示,塞来昔布凝胶配方以6号(海藻酸钠+1.0%氮酮和0.5%薄荷醇)为最佳。同时也表明一种化学物质透过皮肤的量,既与其本身的性质有关,也与透皮剂的种类及性质有关,还与凝胶基质的性质有关。OBJECTIVE To screen the optimum formula of celecoxib gels.METHODS The three factors split-plot experiment design was used to choose the optimal formulation and preparation process of celecoxib gels.Hydroxypropyl methyl cellulose,sodium alginate and carbopol were used as gelling agents,while azone （1.0% and 2.0%） and menthol （0.5% and 1.0%） were used as transdermal agents.The levels of celecoxib permeated from gels into Franz-diffusion cells during 12 hours were detected by high performance liquid chromatography （HPLC）,respectively.Furthermore,the factorial design analysis of variance was carried out to observe the interactions between azone,menthol and each gel.RESULTS The results of split-plot analysis of variance showed that there were significant differences among the 12 h cumulative penetration amount of celecoxib form hydroxypropyl methyl cellulose,sodium alginate and carbopol.Azone and menthol both enhanced the transdermal penetration of celecoxib.Moreover,there were significant interactions between azone,menthol and each gel.The results of factorial design analysis of variance showed that 12 h penetration amount of celecoxib was promoted by azone alone or combined with menthol in hydroxypropyl methyl cellulose gel,but not menthol alone.In sodium alginate gel,the 12 h penetration amount of celecoxib was promoted by azone and/or menthol,which exerted synergistic action.There was little effect of the two transdermal agents together or alone on celecoxib penetration amount in carbopol gel.CONCLUSION The optimal formulation of celecoxib gel is sodium alginate mixed with 1.0% azone and 0.5% menthol.The transdermal penetration amount of celecoxib is not only related to its own nature,but also related to the properties of transdermal agents and gels.

关 键 词：塞来昔布 透皮吸收 月桂氮芯卓酮 薄荷醇 裂区设计 凝胶 

分 类 号：R96[医药卫生—药理学]