Krishnaiah Y S R, Kumar M Shiva, Raju V, Lakshmi M, Rama B
Department of Pharmaceutics, Faculty of Pharmacy, Kuwait University, Kuwait.
Drug Deliv. 2008 May;15(4):227-34. doi: 10.1080/10717540802006633.
The aim of this investigation was to study the effect of an ethanol-water solvent system and ehtanolic solution of menthol on the permeation of ondansetron hydrochloride across the rat epidermis in order to select a suitable ethanol-water vehicle and optimal concentration of menthol for the development of a transdermal therapeutic system. The solubility of ondansetron hydrochloride in ethanol, water and selected concenetrtaion of ethanol-water vehicles (20:80 v/v, 40:60 v/v and 60:40 v/v) was determined. The effect of these solvent vehicles, containing 1.5% w/v of ondansetron hydrochloride, on the in vitro permeation of the drug was studied across the rat epidermis. The highest permeation was observed from 60% v/v of ethanol-water vehicle that showed highest solubilty. Hence, the hydroxypropyl cellulose (HPC) (2% w/w) gel formulations containing 1.5% w/w of ondansetron hydrochloride and selected concentrations of menthol (0, 2, 4, 8 and 10% w/w) were prepared using 60% v/v of ethanol-water vehicle, and subjected to in vitro permeation of the drug across rat epidermis. The transdermal permeation of ondansetron hydrochloride was enhanced markedly by the addition of menthol to HPC gel drug reservoir formulations. A maximum flux of ondansetron hydrochloride (77.85 +/- 2.85 mu g/cm(2.)h) was observed with a mean enhancement ratio of 13.06 when menthol was incorporated at a concentration of 8% w/w in HPC gels. However, there was no significant increase in the drug flux with 10% w/w menthol when compared to that obtained with 8% w/w of menthol in HPC gel formulations. The results suggest that 2% w/w HPC gel drug reservoir formulation, prepared with 60% v/v ethanol-water, containing 8% w/w of menthol provides an optimal transdermal permeation of ondansetron hydrochloride.
本研究的目的是研究乙醇 - 水溶剂系统和薄荷醇乙醇溶液对盐酸昂丹司琼透过大鼠表皮的渗透作用，以便为透皮治疗系统的开发选择合适的乙醇 - 水载体和薄荷醇的最佳浓度。测定了盐酸昂丹司琼在乙醇、水和选定浓度的乙醇 - 水载体（20:80 v/v、40:60 v/v和60:40 v/v）中的溶解度。研究了这些含有1.5% w/v盐酸昂丹司琼的溶剂载体对药物在大鼠表皮上的体外渗透作用。从显示出最高溶解度的60% v/v乙醇 - 水载体中观察到最高的渗透率。因此，使用60% v/v乙醇 - 水载体制备了含有1.5% w/w盐酸昂丹司琼和选定浓度薄荷醇（0、2、4、8和10% w/w）的羟丙基纤维素（HPC）（2% w/w）凝胶制剂，并使其进行药物在大鼠表皮上的体外渗透。向HPC凝胶药物储库制剂中添加薄荷醇可显著增强盐酸昂丹司琼的透皮渗透。当薄荷醇以8% w/w的浓度加入HPC凝胶中时，观察到盐酸昂丹司琼的最大通量为（77.85±2.85μg/cm²·h），平均增强比为13.06。然而，与HPC凝胶制剂中8% w/w薄荷醇相比，10% w/w薄荷醇时药物通量没有显著增加。结果表明，用60% v/v乙醇 - 水制备的、含有8% w/w薄荷醇的2% w/w HPC凝胶药物储库制剂能提供盐酸昂丹司琼的最佳透皮渗透。
