裂区设计探讨萘丁美酮凝胶的最佳配方

Optimization of the formula of Nabumetone gels by Split-plot experiment design

目的以川芎挥发油和氮酮为透皮吸收剂,寻找萘丁美酮凝胶的最佳配方。方法运用三裂式裂区设计,将羟丙基甲基纤维素、海藻酸钠、卡波姆等基质作为主区,透皮吸收剂氮酮(1.0%、2.0%)为副处理,透皮吸收剂川芎挥发油(1.0%、3.0%)为亚副处理,重复3次试验。用改良的Franz扩散池进行奈丁美酮的透皮实验,采用HPLC法测定透过液中萘丁美酮的浓度,并计算其12 h的累积透皮释放量。结果不同区组萘丁美酮透过皮肤的效果无差异,但不同基质间存在明显差异;氮酮、川芎挥发油、基质之间有明显的协同交互作用。以羟丙基甲基纤维素和卡波姆为基质时,川芎挥发油、氮酮都可明显促进萘丁美酮透过皮肤,两者之间存在协同增效作用;以海藻酸钠为基质时,氮酮、川芎挥发油并不促进萘丁美酮透过皮肤,二者之间无明显的交互作用。结论萘丁美酮凝胶配方以12号(卡波姆+2%氮酮+3%川芎挥发油)最佳,提示药物的透皮量不仅与药物性质有关,还与透皮吸收剂的性质及基质的种类和性质有关。

OBJECTIVE To screen the optimal formula of Nabumetone gels which uses azone and aetherolea from Chuanxiong as penetration enhancers.METHODS The three factors Split-plot experiment design was used to obtain the optimal formulation and preparation process of nabumetone gels.Hydroxypropyl methyl cellulose,sodium alginate and carbopol were used as gelling agents,while azone(1.0%and 2.0%)and aetherolea from Chuanxiong(1.0%and 3.0%)were used as transdermal agents.The levels of Nabumetone permeated from gels into Franz-diffusion cells during 12 hours were detected by HPLC,respectively.RESULTS There was no significant difference among different groups in the 12 h cumulative penetration amount of Nabumetone.However,there were significant differences among hydroxypropyl methyl cellulose,sodium alginate and carbopol.There were significant interactions among azone,aetherolea from Chuanxiong and each gel.The azone and aetherolea from Chuanxiong both enhanced the transdermal penetration of Nabumetone in hydroxypropyl methyl cellulose gel and carbopol gel.In sodium alginate gel,azone and aetherolea from Chuanxiong had no alone or synergistic effect on promoting 12 h penetration amount of Nabumetone.CONCLUSION The optimal formulation of Nabumetone gel is carbopol with 2.0%azone and 3.0%aetherolea from Chuanxiong.The transdermal penetration amount of Nabumetone is related to not only its own nature,but also the properties of transdermal agents and gels.