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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 find the best formula for celecoxib (CLX) gel. Methods: Three-split split zone design was adopted. The main areas were hydroxypropylmethyl cellulose, sodium alginate and carbomer. The secondary treatment was two kinds of transdermal agents (Azone) Levels (1.0% and 2.0%), sub-subtreatments were transdermal menthol at both levels (0.5% and 1.0%), and the experiment was repeated 3 times. A modified Franz diffusion cell was used. The celecoxib formulation with different formulations was used as a permeation enhancer, and the cumulative 12-h drug release (Q) was determined and calculated by HPLC. RESULTS: The split-zone analysis showed no significant difference between the groups, but there was a significant difference between the various substrates; transdermal Azone and menthol all play a very important role in promoting the passage of CLX through the skin. Azone, There was a significant synergistic interaction between menthol and matrix. There was a significant synergistic interaction between menthol and azone, as well as menthol, matrix and azone. Further analysis of variance in factorial design revealed that azone plays a major role in promoting CLX penetration through the skin in hydroxypropylmethylcellulose-based gels; menthol has no apparent effect on CLX penetration through the skin But the combination of azone and menthol shows a significant synergistic effect of CLX through the skin. In sodium alginate-based gels, azone and menthol significantly promoted the penetration of CLX through the skin; the combination of the two led to a significant synergistic effect of CLX through the skin. In the carbomer-based gels, neither Azone nor Menthol promoted the penetration of CLX through the skin. There was no significant synergism or antagonism between Azone and Menthol. CONCLUSIONS: The results of this study suggest that celecoxib gel formulation No. 6 (sodium alginate + 1.0% azone and 0.5% menthol) is the best. It also shows that the amount of a chemical that penetrates the skin is both related to its own properties, to the type and nature of the transdermal agent, and to the nature of the gel matrix.