盐酸丁卡因凝胶的制备及评价研究

Preparation and evaluation of tetracaine hydrochloride gel

目的通过体外经皮渗透试验和药效学评价研究,筛选盐酸丁卡因凝胶的最佳处方。方法采用Valin-Chien双室渗透扩散池,以大鼠离体皮肤为透过介质,以8 h的累积渗透量为指标,考察促渗剂氮酮、丙二醇及中和剂三乙醇胺用量对体外透皮性能的影响,筛选出最优处方。并采用小鼠热板法对最佳处方制备的凝胶与市售制剂进行对比,进行药效学评价。结果最优处方的组成为:盐酸丁卡因5 g,卡波姆1 g,乙醇20 g,聚山梨酯-80 6 g,氮酮1 g,丙二醇10 g,三乙醇胺6 g,纯化水补足至100 g。以最优处方制得的凝胶8 h的累积渗透量和渗透速率分别为(416.9±9.95)μg/cm,(69.18±1.27)μg/(cm·h)。与市售制剂相比较,小鼠痛阈值在给药后2 h内显著提高。结论制得的盐酸丁卡因凝胶基本性质良好,具有较佳的体外经皮渗透性,可进一步开发利用。

Objective To optimize the formulation of tetracaine hydrochloride gel and evaluate its characters both in vitro and in vivo.Methods The effects of azone amount, propylene glycol amount, and triethanolamine amount on the permeation ability, cumulative permeation rate and steady-state permeation rate at 8 h of tetracaine hydrochloride gel were evaluated using the Valin-Chien permeation cell with isolated skin. The pharmacodynamics of the optimized tetracaine hydrochloride gel was also evaluated in mice compared with the commercial preparation.Results The optimal formulation was composed with 5 g tetracaine hydrochloride, 20 g ethanol, 6 g Tween 80, 1 g azone, 10 g propylene glycol, 6 g triethanolamine, and purified water to 100 g. The accumulative permeation amount and penetration rate of the optimal tetracaine hydrochloride gel were(416.9 ± 9.95)μg/cm and(69.18 ± 1.27)μg/(cm·h) at 8 h. The pain threshold of mice was significantly improved within 2 h after administration of the optimal tetracaine hydrochloride gel compared with that of the commercial preparation.Conclusion The ideal properties, better transdermal permeation in vitro and increased pharmacodynamics in mice were observed for the optimal tetracaine hydrochloride gel, which indicated that the tetracaine hydrochloride gel in this paper could be further developed and utilized.