Abstract
The study aimed to enhance the transdermal permeation of diclofenac sodium using combined strategy of constant voltage iontophoresis (CVI) and chemical penetration enhancers (CPE). Four hydrogels of diclofenac sodium were formulated with the key CPE and hydroxyethyl cellulose (HEC) as a viscosity imparting agent. In vitro permeation studies of the hydrogels indicated CVI significantly increased (ANOVA, P < 0.05) the steady state flux of diclofenac sodium through the porcine skin in the order geraniol (F1) > l-menthol (F2) > thymol (F3) > SLS-urea (F4) compared to the Fc (Passive control) under the applied voltage. F1 was identified as the lead formulation as an overall increase in steady state flux of 5.157 fold compared to Fc was observed at 1.5V. Pharmacokinetic studies in rats indicated that CVI at 1.5V following application of the lead formulation increased the Cmax and AUC0-8h by ∼3.5 folds compared to passive treatment. The higher systemic levels of diclofenac are likely to enhance the drug concentration in synovial fluid which is the site of action in most musculoskeletal disorders. The results of the study indicate that CVI can effectively deliver therapeutic amounts of diclofenac sodium transdermally to relieve chronic deep-seated muscular pain in several rheumatic disorders.
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