Formulation and evaluation of iontophoretic patch System of diclofenac salts

Abstract

Chronic pain is considered to be a major burden prevailing across the globe arising from newlinevarious musculoskeletal disorders. Diclofenac is used as first line drug for treatment of MSK newlinedisorders. However, most of the topical and transdermal preparations of diclofenac are found to newlinebe less effective due to poor permeation of the drug. Therefore, the purpose of this work was to newlineenhance the transdermal delivery of diclofenac salts by constant voltage iontophoresis (CVI). In newlinevitro screening studies in Franz diffusion cell using porcine skin as barrier indicated that newlinechemical penetration enhancers (CPE) like 5% terpenes (geraniol, l-menthol and thymol) and newlineSLS (5%)-urea (20%) were found to significantly (ANOVA, P lt 0.05) improve the permeation newlineof diclofenac salts at 1.5V. Bioadhesive hydrogels were formulated including the key CPE and newlinehydroxyethyl cellulose (HEC) as matrix former. newlineCVI was found to increase the iontophoretic efficiency in the order of geraniol gt l-menthol newlinegt thymol gtSLS-urea at the applied voltage. CVI was able to increase the permeation of newlinediclofenac sodium from lead formulation that contained geraniol (F newline) by 5.16 and 5.28 fold at newlinevoltage of 1.5 and 3.0 V respectively compared to passive (F newlineXX newline newlineC newline1 newline). Similarly, CVI increased the newlinepermeation of diclofenac potassium from lead formulation that had geraniol (K newline) by 4.73 and newline5.23 at voltage of 1.5 and 3.0 V respectively compared to passive (K newlineC newline). newlineIn vivo studies in rat indicated that CVI following application of lead formulations of newlinediclofenac significantly suppressed (ANOVA, P lt 0.001) the carrageenan induced oedema newlinecompared to the passive treatment at all time points throughout the study that lasted for 8 h. newlinePharmacokinetic studies in rats indicated that CVI at 1.5V following application of lead newlineformulation of diclofenac sodium containing geraniol was found to increase the C newline by ~ 3.5 folds compared to the passive treatment. The higher systemic levels of diclofenac are newlinelikely to enhance the drug concentration in the synovial fluid which eventual