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

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 (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. 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. .

Optimization of different cultural conditions for m-cresol degradation by free and immobilized bacillus laterosporus cells

Optimization of the cultural conditions that facilitate the degradation of m-cresol by a locally isolated bacterial strain Bacillus laterosporus free and entrapped cells was attempted. Bacterial cells entrapped in 2% Ca-allginate beads were more active than free cells and showed a 20% higher rate of m-cresol degradation. Medium No. 1 was most favorable for m-cresol utilization. Supplementing the medium with yeast extract stimulated degradation especially at concentration 0.2 g/l. Optimum concentration of ammonium salts, phosphate salts and magnesium sulfate were 3 g/l and 1.5 g/l, respectively. Optimum concentration of trace elements was 4 ml/l and its omission reduced the rate of degradation. Initial pH of the medium that gave the highest rate of degradation was pH 7 and incubation temperature of 35C. Addition of some amino acids to the mineral medium did not improve degradation rate. The best alginate concentration was 2% and the optimum quantity of beads was 20 ml/ 100 ml medium. The rate of degradation increased by increasing the m- cresol concentration up to 500 mg/l, while higher concentrations [1 g/l] decreased the degradation ability of the entrapped cells