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  • Title: Delivery of a classical antihypertensive agent through the skin by chemical enhancers and iontophoresis.
    Author: Nair A, Reddy C, Jacob S.
    Journal: Skin Res Technol; 2009 May; 15(2):187-94. PubMed ID: 19622129.
    Abstract:
    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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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