Synergistic effect of iontophoresis and chemical enhancers on transdermal permeation of tolterodine tartrate for the treatment of overactive bladder

Abstract

Purpose: The objective of the study was to evaluate the synergistic transdermal permeation effect of chemical enhancers and iontophoresis technique on tolterodine tartrate (TT) transdermal gel and to evaluate its pharmacokinetic properties. Materials and Methods: Taguchi robust design was used for optimization of formulations. Skin permeation rates were evaluated using the Keshary-chein type diffusion cells in order to optimize the gel formulation. In-vivo studies of the optimized formulation were performed in a rabbit model and histopathology studies of optimized formulation were performed on rats. Results: Transdermal gels were formulated successfully using Taguchi robust design method. The type of penetration enhancer, concentration of penetration enhancer, current density and pulse on/off ratio were chosen as independent variables. Type of penetration enhancer was found to be the significant factor for all the responses. Permeation parameters were evaluated when maximum cumulative amount permeated in 24 hours (Q 24 ) was 145.71 ± 2.00µg/cm 2 by CIT4 formulation over control (91.89 ± 2.30µg/cm 2 ). Permeation was enhanced by 1.75 fold by CIT4 formulation. Formulation CIT4 containing nerolidol (5%) and iontophoretic variables applied (0.5mA/cm 2 and pulse on/off ratio 3:1) was optimized. In vivo studies with optimized formulation CIT4 showed increase in AUC and T1/2 when compared to oral suspension in rabbits. The histological studies showed changes in dermis indicating the effect of penetration enhancers and as iontophoresis was continued only for two cycles in periodic fashion so it did not cause any skin damage observed in the slides. Conclusion: Results indicated that iontophoresis in combination with chemical enhancers is an effective method for transdermal administration of TT in the treatment of overactive bladder.

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“…A cell similar to the one designed by Keshary and Chein was used for permeation studies and it had a water jacket for maintaining the temperature at 37±0.5°C [33,34]. The vertical double-walled diffusion cell consisted of two half cells with diffusion areas of 9.0 cm 2 and the capacity of the receiver chamber was 40 ml.…”