利多卡因纳米乳制备及体外经皮吸收的实验研究  

Preparation of lidocaine nanoemulsion and its transdermal absorption by rat skin ex vivo

作　　者：朱晓亮[1] 李国锋[2] 曾抗[1] 陈志良[2] 

机构地区：[1]南方医科大学南方医院皮肤科,广东广州510515 [2]南方医科大学南方医院药学部,广东广州510515

出　　处：《南方医科大学学报》2010年第3期451-454,共4页Journal of Southern Medical University

基　　金：国家自然科学基金(30902019);广东省医学科研基金(A2008414)

摘　　要：目的制备5%利多卡因纳米乳,考察利多卡因纳米乳对离体大鼠皮肤的透皮能力。方法伪三元相图法结合origin软件分析确定制备5%利多卡因纳米乳的最佳Km值(表面活性剂/助表面活性剂比值)及各组份比例;Zeta粒度分析仪测定纳米乳粒径大小及分布范围;透射电镜观察纳米乳形态及体系类型;采用改良Franz扩散池联用高效液相色谱(HPLC)比较含5%利多卡因的纳米乳、凝胶和酊剂的累积透皮吸收量Q和表观皮肤透皮速率(Kp)值,分析利多卡因纳米乳的透皮渗透类型。结果利多卡因纳米乳平均粒径为(29.8±14.4)nm,其中98%的粒径范围介于15.1～45.5nm之间,2%介于77.9～261.3nm之间;纳米乳体系为大小不均的球形多分散体系;纳米乳的Kp值(3.07±0.74cm·h-1)显著高于凝胶[(1.27±0.35)cm·h-1]和酊剂[(0.97±0.18)cm·h-1],纳米乳的透皮速率为[(69.82±7.48)μg·cm-2·h-1],透皮过程符合零级释放动力学过程。结论伪三元相图法结合origin软件分析确定纳米乳各组份比例的方法简便、准确,马尔文粒径测定结合透射电镜观察测定纳米乳的粒径、分布、形态及体系类型的方法较为全面,利多卡因纳米乳有较强的透皮能力,有望成为新型皮肤局麻透皮给药制剂。Objective To prepare lidocaine nanoemulsion and investigate its transdermal delivery ability in vitro. Methods The optimal Km （surfactant/cosurfactant） value and the component proportion were determined by pseudoternary phase diagrams combined with Origin software analysis. The diameter and distribution range were detected by Zeta particle size analysis instrument, and the morphology of the nanoemulsion was observed by electron microscope. The permeation flux of lidocaine was determined in vitro using the modified Franz diffusion cell combined with HPLC, and the cumulative transdermal absorption amount and the apparent skin transdermal velocity were compared among nanoemulsion, gel and tincture containing 5% lidocaine. The permeation mode of lidocaine nanoemulsion was analyzed. Results The average drop size of lidocaine nanoemulsion was 29.8±14.4 nm, and 98% of the drop sizes ranged from 15.1 to 45.5 nm and 2% from 77.9 to 261.3 nm. The nanoemulsion drop showed a spherical morphology in a polydisperse system. The Kp value of the nanoemulsion （3.07±0.74 cm/h） was significantly higher than that of gel （1.27±0.35 cm/h） and tincture （0.97±0.18 cm/h）, and the permeation rate of the nanoemulsion was 69.82±7.48 μg·cm-2·h-1, which fitted the the Zero-order release dynamic procedure. Conclusions The component proportion of lidocaine nanoemulsion can be conveniently obtained through pseudoternary phase diagrams and Origin software analysis, and the drop size, distribution, morphology and system type can be determined by Malvern Zetasizer combined with electron microscopy. The results also indicate that the nanoemulsion system with high permeation rate may provide a new promising means for local anesthesia.

关 键 词：利多卡因 纳米乳 透皮吸收 

分 类 号：R943[医药卫生—药剂学]