Separation and Simultaneous Quantitation of Tolterodine Tartrate and Tamsulosin Hydrochloride in Capsule Formulation by using Stability-Indicating RP-HPLC-DAD Method

In the present work, a precise, accurate and selective stability-indicating RP-HPLC method has been developed and validated according to International Conference on Harmonization guidelines Q2-(R1) for the simultaneous quantitative determination of Tolterodine tartrate and Tamsulosin hydrochloride in bulk and its capsule formulation. The chromatographic separation was achieved on Hypersil octadecyl silane C18 (250 x 4.6mm, 5 μm) column at room temperature and mobile phase comprised of methanol: 0.05 M phosphate buffer, pH 7.0 in the ratio of 90:10 V/V. The flow rate of mobile phase was set at 1.0mL/min and compounds were monitored at 255nm using photodiode array detector. Tamsulosin hydrochloride and Tolterodine tartrate retention time were found to be 4.15±0.2 min and 8.42±0.2 min, respectively. The drug substances and products were subjected to acid hydrolysis, alkali hydrolysis, oxidative hydrolysis, photolytic and thermal degradation. The percent degradation of drugs was calculated in all stressed conditions. The analytical method validation parameters such as linearity, accuracy, precision, detection limits, quantitation limits and robustness indicate that drug substances and products were efficiently separated in present of their degradants and successfully applied for the routine analysis of Tolterodine tartrate and Tamsulosin hydrochloride in bulk and its capsule formulation in the quality control laboratory.

FEATURES TREATMENT OF IDIOPATHIC OVERACTIVE BLADDER WITHOUT DETRUSOR OVERACTIVITY

Introduction. The basis syndrome Overactive Bladder (OB) is detrusor overactivity (DO) – urodynamic concept that refers to spontaneous or provoked by involuntary detrusor contractions during the filling phase Bladder. Currently, there are two main forms of DO: neurogenic and idiopathic. The purpose was to evaluate the effectiveness of monotherapy with M-anticholinergic Tolterodine tartrate and its combined administration with the cyclic structural analogue of g-aminobutyric acid Gabantin in patients with idiopathic overactive bladder without detrusor overactivity (IOB). Object and methods. Patients were divided into two groups: group A – 31 patients (19 patients with IOB without Urinary Incontinence (UI) and 12 patients with UI and group B – 32 patients (21 patients with IOB without UI and 11 patients with UI). According to the study design, patients in group A were prescribed M-anticholinergic therapy Tolterodine tartra. Patients in group B received combined therapy with Tolterodin tartrate and Gabapentin for a total course for 8 weeks. Results and discussions. Analysis of the results in group A showed that this type of treatment does not lead to significant improvement. However, 3 patients (9.67 %) had a good result, and 7 patients (22.58 %) had a satisfactory result, the rest (21 patients, 67.74 %) had an unsatisfactory result. But among patients in the group B general, a satisfactory result of treatment was noted in 24 (75 %) patients. An unsatisfactory result was observed in 8 (25 %) patients. Conclusions. Monotherapy with M-anticholinergic in patients with IOB and the absence of DO has little effectiveness and is implemented mainly by reducing Pollakiuria. The symptoms of Urgency are resolved moderately (in 22.58 % of patients) and extremely rarely in full (in 9.67 % of patients). The proposed method of treatment by the combined administration of Tolterodine tartrate and Gabapentin allows to achieve a significantly more pronounced clinical effect manifested in a decrease in Pollakiuria by 64.17 %, Nocturia by 82.18 % and Urgency by 81.40% and UI by 80.66 %.

Preparation and Evaluation of Sustained Release Matrix Tablets of Tolterodine Tartrate Using Guggul Resin

The present study is based on preparation of sustained release matrix tablets of tolterodine tartrate (for overactive bladder treatment) using guggul resin. Tolterodine tartrate is a highly soluble drug, to increase the duration of action the release of the drug has to be sustained. Natural resin is used as a polymer to sustain the release of drug, which was isolated from guggul gum by petroleum ether. Natural polymers are economical, biodegradable and can be chemically modified. Different ratios of drug and guggul resin were tried in the formulation of sustained release matrix tablets of tolterodine tartrate. Wet granulation technique was adopted for preparation of tolterodine tartrate granules, showed good flow properties and compressibility. The fabricated tablets were evaluated for various physicochemical characteristics and in vitro release studies like hardness, thickness, weight variation, friability, drug content and content uniformity were found to be within the limits. The drug release of optimized formulation (F6) was fitted to various kinetic models and the R2 value is 0.988 and the n value of drug release is 0.787. Therefore, the drug release follows zero order with non-fickian diffusion. The mechanism of drug release involves erosion and diffusion. Stability studies were performed for the optimized formulation as per ICH guidelines climatic zone III and were found to be stable with insignificant changes in physicochemical characteristics and in vitro release studies.Bangladesh Pharmaceutical Journal 21(1): 24-34, 2018

DEVELOPMENT AND EVALUATION OF NOVEL DRUG DELIVERY SYSTEM OF TOLTERODINE TARTRATE

Objective: Tolterodine tartrate (tolterodine) is used for treating overactive bladder (OAB) with symptoms of urinary frequency, urgency and leakage. Tolterodine is an antimuscarinic (anticholinergic) agent. It works by blocking a chemical that causes contractions of the bladder. Present work involved development of a novel drug delivery system of tolterodine intended to be taken once daily.Methods: Extended release (ER) pellets of tolterodine were prepared and optimized for in vitro drug release. Subsequently, these pellets were filled into a suitable sized capsule. The resulting capsules were evaluated for in vitro drug release. Optimized formulation was subjected to accelerated stability studies for 3 mo and was evaluated for description, average weight, assay and drug release.Results: The optimized ER capsule exhibited similar dissolution profile as that of the reference listed drug (RLD), with approximately 45%, 75% and more than 80% release in 3 h, 5 h and 7 h respectively. Accelerated stability studies indicated good physical and chemical stability of the formulation.Conclusion: ER formulation of tolterodine was optimized and can be used as once a day dosage, reducing the frequency of administration when compared with the immediate release formulation. The developed formulation exhibited similar behavior as that of reference formulation Detrol LA marketed in the US.