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. .

Effectiveness of tolterodine in nonneurogenic voiding dysfunction.

The efficacy of tolterodine was analysed in children with non-neurogenic voiding dysfunction, using dysfunctional voiding symptom score (DVSS). Of 44 patients (mean age 9.3 yrs; M:F = 25:19), 36 received long acting tolterodine tartrate at a dose of 2mg OD and 8 at a dose of 4mg OD. The mean (SD) DVSS before and after the treatment was 17.1 (2.8) and 12.0 (2.4). There was a significant improvement in the mean DVSS score at the end of the treatment (Students t test P < 0.01). The dysfunctional symptoms were cured in 28(63.6 %), improved in 14(31.8 %) and failed to show improvement in 2 (4.6 %). Over all 95 % were compliant with the single daily medication. Our results demonstrate that long acting tolterodine is effective in children with voiding dysfunction. The single daily dose has good compliance and minimal side effect profile.

Derivative spectrophotometry for simulataneous analysis of chlorpheniramine maleate, phenylephrine HCI, and phenylpropanolamine HCI in ternary mixtures and pharmaceutical dosage forms

In this study, different derivative spectrophotometric methods are proposed for the simultaneous determination of chlorpheniramine maleate [CP], phenylephrine HCl [PE] and phenylpropanolamine HCl [PP] in their ternary mixtures and in pharmaceutical dosage forms. Spectra of single component and ternary mixtures of various concentrations and combinations from zero- to fourth-derivation were obtained. Also the spectra of the excipients including lactose, starch, and microcrystalline cellulose were obtained to study the possible interference from matrices. Zero-crossing derivative spectrophotometry based on recording the second-derivative curve for PE at 286.5 nm and fourth-derivative curve for PP at 220 nm were used for determining each component. Third component, CP, was determined by measuring absolute amplitudes at 265.8, 262.2, 269.5, and 273.8 nm in its second derivative spectra. Results showed that the matrices have no interferences. The calibration curves were linear in the range of 1-8 micro g/ml for PE; 5-30 micro g/ml for PP; and 2-8 micro g/ml for CP. The limits of detection were 0.2 micro g/ml for PE, 0.1 micro g/ml for PP, and 0.3 micro g/ml for CP. The mean percentage recoveries obtained for different synthetic mixtures by using this method were 95.3% with coefficient of variation of 4.3% for PE, 101.5% with coefficient of variation of 1.4% for PP, and 99.4% with coefficient of variation of 1.5% for CP. This method has been applied successfully for the determination of PE and PP in its combination with CP in Antihistamine Decongestant tablets with a high percentage of recovery, good accuracy and precision

Role of tolterodine in management of over active bladder [OAB] in different age groups

To assess the efficacy of tolterodine in management ofnon neurogenic overactive bladder in all ages and both sexes, also to evaluate the expected side effects and compliance of the patients with such anticholinergic drug. In prospective study one hundred patients 43 females, 50 males, and 7 children entered in the study all came complaining of symptoms of OAB to the urology clinic, all had a base line pressure flow studies except the children. After the initial evaluation, all patients were treated by tolterodine [Detrusitol] 2mg twice daily and in some resistant cases it may increase into three times daily, basically for three months period extends to 6 months in partially responded patients and repeated for those with relapsed after being good responders. Of the 100 patients, complete response occurred in 63 [63%], partial response in 27 [27%], and no response in 10 [10%], with the female population showed the majority of responders, followed by non bladder outflow obstruction [B.O.O] male patients, also in pediatric patients it shows considerable response

Sustained release phenylpropanolamine hydrochloride from ATO 888 matrix

Sustained release phenylpropanolamine HCl tablets were prepared with compritol as a retardant material. The effects of varying wax levels and methods of matrix formation on drug release were investigated. Also the compaction profiles were recorded for all formulations. The amount of drug in the formula was held constant (10 per cent w/w), while the wax level was varied from 10 per cent to 50 per cent w/w. Two methods were used for the preparation of drug: wax systems; physical mixture and solid dispersion. The drug release from tablets containing 10 per cent Compritol and prepared by solid dispersion was 97 per cent after six hours of testing dissolution. Tablets prepared with 30 per cent wax released 72 per cent of the drug, while tablets containing 50 per cent wax released only 30 per cent of the drug after six hours. Tablets prepared by physical mixture gave higher drug release than tablets prepared by solid dispersion method. The incorporation of Compritol decreased the ejection forces of tablets during compaction. The drug release from tablets prepared by solid dispersion followed the diffusion controlled model described by Higuchi for inert porous matrix