title: Synergistic effect of iontophoresis and chemical enhancers on transdermal permeation of tolterodine tartrate for the treatment of overactive bladder.
abstract: OBJECTIVE
  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.
  
  
  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 (Q24) was 145.71 ± 2.00µg/cm² by CIT4 formulation over control (91.89 ± 2.30µg/cm²). Permeation was enhanced by 1.75 fold by CIT4 formulation. Formulation CIT4 containing nerolidol (5%) and iontophoretic variables applied (0.5mA/cm² 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.
  
  
  CONCLUSIONS
  Results indicated that iontophoresis in combination with chemical enhancers is an effective method for transdermal administration of TT in the treatment of overactive bladder.
authors.affiliation: G. Pulla Reddy College of Pharmacy, Osmania University, Hyderabad 500-028, India. drlakshmisuresh@gmail.com
authors.forename: D
authors.initials: D
authors.lastname: Prasanthi
authors.forename: P K
authors.initials: PK
authors.lastname: Lakshmi
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003408:Cresols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004357:Drug Synergism; D005782:Gels; D007478:Iontophoresis / Q000379:methods*; D008297:Male; D023421:Models, Animal; D010665:Phenylpropanolamine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012869:Skin Absorption; D013997:Time Factors; D000068737:Tolterodine Tartrate; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*; D064804:Urological Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D001559:Benzhydryl Compounds; D003408:Cresols; D005782:Gels; D064804:Urological Agents; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate