Nair Anroop, Reddy Chandrasekhar, Jacob Shery
PES College of Pharmacy, Hanumanth Nagar, Bangalore, Karnataka, India.
Skin Res Technol. 2009 May;15(2):187-94. doi: 10.1111/j.1600-0846.2009.00350.x.
BACKGROUND/PURPOSE: Oral therapy with antihypertensive agents is generally associated with severe GI side effects and low patient compliance. Therefore, development of a method of drug delivery that maintains the proper drug level for a prolonged period without adverse effects is required. Thus, transdermal delivery has all the necessities that are required for delivery of classical antihypertensive agents. However, the different approaches to enhance the transport of atenolol through intact skin have not resulted in a remarkable improvement.
The effect of the drug concentration and a binary system (water-ethanol) on the atenolol flux was investigated. Further, the effects of chemical enhancers (menthol, oleic acid, polyethylene glycol 400, sodium lauryl sulphate, di methyl formamide and N-methyl-2-pyrrolidone) at different concentrations and their combined effects with iontophoresis were examined.
Among the binary systems, the highest flux was obtained when 75% v/v ethanol in water was used. Atenolol flux enhanced significantly (P<0.001) at the 5% w/v concentration among all the enhancers studied. It was also observed that the combination of iontophoresis with oleic acid (5% w/v) showed the maximum benefit with a steady-state flux of 2.66 mumol/cm(2)/h.
The combination of iontophoresis with permeation enhancers was found to be promising in delivering atenolol across the skin, and the highest permeation was attained when oleic acid was combined with iontophoresis. The in vitro flux value obtained (when oleic acid combined with iontophoresis) was 0.71 mg/cm(2)/h, which points to the fact that a therapeutically effective concentration can be attained with 1.2 cm(2) of skin contact area.
背景/目的：口服抗高血压药物治疗通常会伴有严重的胃肠道副作用，且患者依从性较低。因此，需要开发一种能长时间维持适当药物水平且无不良反应的给药方法。经皮给药具备递送传统抗高血压药物所需的一切必要条件。然而，增强阿替洛尔透过完整皮肤转运的不同方法并未带来显著改善。
研究了药物浓度和二元体系（水 - 乙醇）对阿替洛尔通量的影响。此外，还考察了不同浓度的化学渗透促进剂（薄荷醇、油酸、聚乙二醇400、十二烷基硫酸钠、二甲基甲酰胺和N - 甲基 - 2 - 吡咯烷酮）的作用以及它们与离子导入联合使用的效果。
在二元体系中，使用75%（v/v）乙醇水溶液时获得了最高通量。在所研究的所有渗透促进剂中，阿替洛尔通量在5%（w/v）浓度时显著增强（P<0.001）。还观察到，离子导入与油酸（5%，w/v）联合使用时效果最佳，稳态通量为2.66 μmol/cm²/h。
发现离子导入与渗透促进剂联合使用在阿替洛尔经皮递送方面具有前景，油酸与离子导入联合使用时达到最高渗透率。所获得的体外通量值（油酸与离子导入联合使用时）为0.71 mg/cm²/h，这表明通过1.2 cm²的皮肤接触面积可达到治疗有效浓度。
