No abstract

BackgroundTramadol hydrochloride is available as 50 mg immediate-release (IR) and 100 mg, 200 mg, and 300 mg sustained-release (SR) tablets. The recommended dose of tramadol is 50–100 mg IR tablets every 4–6 hours. The tramadol SR 200 mg tablet is a better therapeutic option, with a reduced frequency of dosing, and improved patient compliance and quality of life. The present study evaluated the bioequivalence of a generic tramadol SR 200 mg tablet.MethodsA comparative in vitro dissolution study was performed on the test and reference products, followed by two separate single-dose bioequivalence studies under fasting and fed conditions and one multiple-dose bioequivalence study under fasting conditions. These bioequivalence studies were conducted in healthy human subjects using an open-label, randomized, two-treatment, two-period, two-sequence, crossover design. The oral administration of the test and reference products was done on day 1 for both the single-dose studies and on days 1–5 for the multiple-dose study in each study period as per the randomization code. Serial blood samples were collected at predefined time points in all the studies. Analysis of plasma concentrations of tramadol and O-desmethyltramadol (the M1 metabolite) was done by a validated liquid chromatography-mass spectrometry analytical method. The standard acceptance criterion of bioequivalence was applied on log-transformed pharmacokinetic parameters for tramadol and its M1 metabolite.ResultsThe ratios for geometric least-square means and 90% confidence intervals were within the acceptance range of 80%–125% for log-transformed primary pharmacokinetic parameters for tramadol and its M1 metabolite in all the three studies.ConclusionThe test product is bioequivalent to the reference product in terms of rate and extent of absorption, as evident from the single-dose and multiple-dose studies. Both the treatments were well tolerated.

A stability-indicating reversed-phase liquid chromatographic method has been developed and validated for simultaneous determination of losartan potassium and ramipril. Separations were achieved using a C18 column with mobile phase consisting of acetonitrile and (0.2% v/v, pH 2.5) aqueous trifluoroacetic acid (45:55, v/v) in isocratic mode at 1 ml/min flow rate. Column effluent was monitored at 210 nm using a UV detector. The method was validated for selectivity, linearity, accuracy, precision, sensitivity and robustness. Novel microwave-assisted forced degradation technique was employed for evaluation of selectivity. The method demonstrated excellent linearity for losartan potassium and ramipril with regression coefficients of 0.9999 and 0.9998, respectively. The linearity range was found to be 62.5-5000 ng/ml and 125-10,000 ng/ml with the mean percentage recoveries of 100.36% (±2.27) and 100.16% (±3.33) for losartan potassium and ramipril, respectively. In a robustness study, a full factorial design revealed that the analytical response remains unaffected by small variations in the critical chromatographic factors. The method was found to be sensitive with quantification limits of 44.30 and 79.93 ng/ml for losartan potassium and ramipril. The method was successfully employed for the determination of losartan potassium and ramipril in commercially available and in-house prepared tablets.