Stability Indicating RP-HPLC Method Development and Validation for the Determination of Solifenacin Succinate in Bulk and its Pharmaceutical Formulation

The current work aims to establish a novel and advanced reverse phase isocratic liquid chromatography system followed by validation and to conduct stability analysis in active pharmaceutical ingredients and formulations for the quantification of Solifenacin Succinate. The optimized elution was achieved with column Sunfire C8 (4.6 x 150mm, 5µm), using the mobile phase of Buffer: Methanol: Acetonitrile in the composition ratio of 45:45:10 v/v. The wavelength of detection was selected as 220nm with 1.0ml/ min flow rate and 30μl injection volume. The retention time of Solifenacin Succinate was found 2.94 min respectively. The method developed has been validated for various analytical parameters according to ICH guidelines. The Linearity was attained at 20 to100 μg/ml of concentration range. The established method was proved as reproducible. The Assay was obtained as 100.40%. The degradation studies were carried out at all degradative conditions and the results of degradation studies denote that the current method was specific, reliable, and economical. Hence, the developed method can be applied for the qualitative and quantitative determination of the selected drug and its commercial formulations.

Transcutaneous electrical nerve stimulation and solifenacin succinate versus solifenacin succinate alone for treatment of overactive bladder syndrome: A double-blind randomized controlled study

Objective We evaluated a combination of transcutaneous electrical nerve stimulation (TENS) and solifenacin succinate versus solifenacin alone in the treatment of overactive bladder (OAB). Methods Ninety-seven female outpatients with OAB were screened for this double-blind randomized controlled study. Eighty-six patients who met our inclusion criteria were divided randomly into two groups. In group A (43 patients), patients received oral solifenacin and “fake” TENS on the foot; in group B (43 patients), patients received oral solifenacin and effective TENS on the foot. Improvements in OAB symptoms were assessed by Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire (OAB-q), voiding diaries and urodynamic tests. 70 of 86 patients (36 in group A, 34 in group B) completed the 2 months of treatment and 3 months of follow-up. Results Statistically, the maximum bladder volume and OAB symptoms of both groups improved significantly after treatment. The improvement in group B was significantly better than that in group A, as indicated by the maximum bladder volume, OAB-q score and voiding diary. Some mild adverse effects were observed, including dry mouth, stomach upset, constipation, muscle pain and local paresthesia. Conclusion The combination of TENS and solifenacin was more effective in improving OAB symptoms than solifenacin alone.

Different antimuscarinics when combined with atomoxetine have differential effects on obstructive sleep apnea severity

The combination of the noradrenergic agent atomoxetine plus the anti-muscarinic oxybutynin has recently been shown to improve upper airway physiology and reduce obstructive sleep apnea (OSA) severity. However, the effects of different anti-muscarinics when combined with atomoxetine is limited. This study aimed to determine the effects of atomoxetine combined with two different anti-muscarinics with varying M-subtype receptor selectivity on OSA severity and upper airway physiology.10 people with predominantly severe OSA completed a double-blind, randomised, placebo-controlled, cross-over trial. Participants completed 3 overnight in-laboratory sleep studies after either 80mg atomoxetine+5mg solifenacin succinate (ato-sol) or 80mg atomoxetine+2mg biperiden hydrochloride (ato-bip) or placebo. OSA severity, ventilatory stability (loop gain), respiratory-arousal threshold (via epiglottic manometry), next day subjective sleepiness (Karolinska Sleepiness Scale:KSS) and alertness were compared between conditions. Neither drug combination altered the apnea/hypopnoea index versus placebo (p=0.63). Ato-sol caused a shift towards milder respiratory events with reduced frequency of obstructive apneas (13±14vs. 22±17events/h; mean±SD, p=0.04) and increased hypopneas during NREM (38±21vs. 24±18events/h, p=0.006) with improved nadir oxygenation versus placebo (83±4vs. 80±8%, p=0.03). Both combinations reduced loop gain by ~10% versus placebo; sleep efficiency and arousal threshold were unaltered. Ato-bip reduced next-day sleepiness versus placebo (KSS=4.3±2.2vs. 5.6±1.6, p=0.03).Atomoxetine+biperiden hydrochloride reduces perceived sleepiness and atomoxetine+solifenacin modestly improves upper airway function in people with OSA but to a lesser extent versus recently published atomoxetine+oxybutynin (broad M-subtype receptor selectivity) findings. These results provide novel mechanistic insight into the role of noradrenergic and anti-muscarinic agents on sleep and breathing and are important for pharmacotherapy development for OSA.

Comparison of the Effects of Solifenacin Succinate for the Treatment of Overactive Bladder with Extended Release Tolterodine

Objective: To compare the therapeutic effects of solifenacin succinate with extendedrelease tolterodine for the treatment of overactive bladder (OAB) in Bangladeshi patients. Methods: A prospective, randomized, single-blind, two-arm, parallel-group, clinicaltrial was conducted in the department of Urology, Bangabandhu Sheikh Mujib MedicalUniversity (BSMMU), Dhaka from January 2013 to June 2014. A total of 65 patientswith OAB were treated with solifenacin succinate 5 mg (experimental group, n=33)and extended release tolterodine 4 mg (control group, n=32), both at night daily for 12weeks. Efficacy and safety variables were assessed and compared with baseline and at 12weeks treatment in between the two groups. Results: At week 12, solifenacin succinate and extended release tolterodine demonstratedreduction in the mean number of micturition (50% vs. 51%), urgency (87% vs. 73%),urge incontinence (89% vs. 71%), nocturia (89% vs. 74%), usage of pads (90% vs.71%) per 24 hours. There was increased in the mean voided volume of each micturitionin both the groups without any difference in between them. The incidence of major adverseevents were dry mouth (15.2% vs. 9.4%), constipation (9.1% vs. 15.6%), and blurredvision (6.1% vs. 3.1%) respectively. Conclusions: Solifenacin succinate had greater efficacy to extended release tolterodine intreating overactive bladder. There were no significant treatment difference between the twogroups in decreasing the number of micturition and increasing the voided volume of eachmicturition and the incidence of major adverse events. All the adverse effects were mild andtransient in nature and discontinuation of medication due to adverse effects were low. Bangladesh Journal of Urology, Vol. 23, No. 1, January 2020 p.76-81