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Publications (4)4.69 Total impact

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    ABSTRACT: To study the bioequivalence of Losartan Potassium Tablets 50 mg manufactured by Micro Labs Ltd. India to Cozaar® Tablets 50 mg, manufactured by Merck Sharp and Dohme Ltd., UK in normal healthy adult subjects under fasting condition along with the comparative safety evaluation of both treatments. The in vitro dissolution studies were carried out on 12 units each of test and reference products using the paddle method and dissolution media like water, 0.1 N hydrochloric acid with pH 1.2, pH 4.5 acetate buffer and pH 6.8 phosphate buffer. An open label, randomized, two-treatment, two-period, two-sequence, crossover bioequivalence study with a washout period of 7 days was conducted in 60 healthy Indian male subjects. Serial blood samples were collected after drug administration in each study period. Plasma concentrations of losartan and losartan acid were determined using a validated LC-MS-MS method. The pharmacokinetic parameters of losartan and losartan acid were determined using a non compartmental model. Occurrence of adverse events, change in systolic blood pressure, diastolic blood pressure, heart rate and QT interval from the baseline to 3.50 h post dose were studied and compared between the two treatments as safety parameters. The in vitro study proved the essential similarity of both the formulations as evident from the similarity factor of > 50% in all the dissolution media. The ratios for geometric least square means and 90% confidence intervals were within the acceptance criteria of 80% to 125% for log transformed C(max), AUC(0-t) and AUC(0-∞) for losartan. No statistically significant difference between the two treatments was observed for either of the safety parameters. The test product Losartan Potassium tablets 50 mg manufactured by Micro Labs Limited, India was bioequivalent to Cozaar® tablets 50 mg, manufactured by Merck Sharp and Dohme Ltd., UK in terms of rate and extent of absorption. Both treatments were well tolerated and had similar non significant effect on the safety parameters.
    International journal of clinical pharmacology and therapeutics 05/2012; 50(5):349-59. · 1.20 Impact Factor
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    ABSTRACT: Tramadol 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. A 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. The 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. The 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.
    Drug Design, Development and Therapy 01/2010; 4:367-74. · 3.49 Impact Factor
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    ABSTRACT: Background and objective: The existing fixed-dose combination, Coartem® (artemether 20 mg and lumefantrine 80 mg) requires 4 tablets per dose and a total of 24 tablets for the six-dose regimen for the treatment of uncomplicated P. falciparum malaria compromising the patient compliance. Also, the cardiotoxicity due to lumefantrine because of its structural similarity with halofantrine remains a matter of debate in therapeutics. To enhance the patient compliance, the fixed-dose combination of artemether/lumefantrine (80/480 mg) is formulated by Sequel Pharmachem Pvt. Ltd. India. In the present study, this fixed dose combination (test product) was evaluated for its bioequivalence to the reference product, Coartem® 20/120 mg (artemether 20 mg and lumefantrine 120 mg) of Novartis Pharma Ltd. with assessment of cardio-hepatic safety. Methods: A randomized, open label, two-treatment, two-period, two-sequence, single-dose, crossover bioequivalence study with comparative safety evaluation was conducted on 72 healthy Indian human subjects under a fed condition. Quantification of artemether, dihydroartemisinin, and lumefantrine was done by a validated LC-MS/ MS method. For bioequivalence, AUC0-240, AUC0-inf and Cmax for artemether and lumefantrine were considered. Safety assessment was done by monitoring vital signs, QTc interval, serum ALT and AST values before and after treatment. Max QTc, baseline-corrected QTcmax, AST and ALT values were considered for statistical comparison between the two treatments. Drug plasma concentrations estimated at identical time points with the ECG recordings were correlated with ECG parameters. Results: The test product was bioequivalent to the reference product as per the standard bioequivalence criteria. There was no clinically significant difference between the two treatments for all the safety parameters. No significant observation suggestive of cardiotoxicity and hepatotoxicity was noted in this study. Conclusion: The test product can be used as a therapeutic option with likely better patient compliance in the treatment of uncomplicated P. falciparum malaria.
    Journal of Bioequivalence & Bioavailability 01/2010;
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    ABSTRACT: Background and Objective: Prolonged pharmacokinetic sampling is a challenge for successful conduction of thebioequivalence studies for drugs having long elimination half-lives. The regulatory authorities have recommended analternative to consider the partial AUC (AUC0-72) for studying bioequivalence. However, the results obtained from suchtruncated approach are not consistent and needs further exploration. We have investigated the suitability of truncatedAUC in the fi eld of bioequivalence.Methods: The bioequivalence studies conducted with conventional approach for Bicalutamide, Topiramate andAmitriptyline having long elimination half-lives were investigated. The pharmacokinetic data obtained from these studieswas truncated at 72hrs and 2 half-lives post dose. The 90% confi dence intervals constructed for the ratios of means oflog-transformed partial AUC (at 72hrs and 2 half-lives post dose) were compared individually with those of the total AUC.The intra-subject variability obtained for partial AUC at 72hrs and 2 half-lives post dose was compared individually forpercentage change from that of the total AUC.Results: No change in the study outcome irrespective of the point of truncation of AUC was observed. The 90%confi dence intervals constructed for the ratio of means of log-transformed partial AUC (at 72hrs and 2 half-lives postdose) were well within the acceptable bioequivalence criteria of 0.8-1.25. The intra-subject variability for AUC was notinfl uenced irrespective of the point of truncation of AUC.Conclusion: Limiting the pharmacokinetic sample collection period to 72 hours in bioequivalence studies for thedrugs having long elimination half-lives is equally accurate and sensitive alternative to the conventional approach.
    Journal of Bioequivalence & Bioavailability 01/2010;