A simple stability indicating reverse phase high performance liquid chromatography method was developed and validated for simultaneous estimation of naproxen and esomeprazole magnesium in combined delayed release dosage form 500/20 mg, 375/20 mg, using a single unit of tablet. Chromatographic separation was achieved with Agilent's high performance liquid chromatography and Xterra RP-18 column, with the mobile phase-1 of perchlorate buffer (pH 8.7): acetonitrile methanol (700:200:100, v/v/v) and mobile phase-2 of per chlorate buffer (pH 8.7): acetonitrile (700:300, v/v) by gradient elution technique. The flow rate was maintained at 1.5 ml/min and the detection wavelength was 305 nm. Naproxen and esomeprazole were eluted at 3.3 min and 6.1 min respectively using the developed method. Analytical method validation was performed according to International Conference on Harmonization Q2 (R1) guidelines. The method was linear in the range of 60-1500 μg/ml for naproxen and 2-60 μg/ml for esomeprazole, with r 2 value of 0.9996 and 0.9997 respectively. The sample recoveries observed were 100.38-101.39% and 99.67-99.94% respectively for naproxen and esomeprazole magnesium, which confirm the non-interference of formulation additives in the estimation. The forced degradation studies were carried out and the stressed samples were analyzed using the developed method. The purity angle of the peak was observed lesser than the threshold angle, which confirms the non-interference from degradants in quantitating naproxen and esomeprazole in bulk and marketed formulation.
Objectives: This research work is aimed to develop bio relevant dissolution method by simulating human gastrointestinal condition at post-prandial state. The quality control dissolution procedure for modified release product using simple buffers of specific pH is not adequate for prediction of in vivo performance. Methods: Percentage of drug absorbed is derived by deconvolution of drug plasma concentration at post-prandial condition using Wagner-Nelson deconvolution method. Quality control dissolution test is performed using office of generic drugs recommended dissolution method. Bio relevant dissolution method is developed using USP Apparatus 3 (reciprocating cylinder), with quality by design approach. A full factorial design of experiment study is performed for optimization of dips per minute and media volume. Separate dissolution method is developed for tamsulosin and dutasteride, since the formulation design and release profile are different for both drugs. Results: The dissolution profile obtained using quality control procedure is observed faster in comparison to percentage of drug absorbed. The bio relevant dissolution method developed for tamsulosin part is, 250ml of Fed state simulated change over dissolution media with 15DPM, based on desirability factor 0.8767 and for dutasteride part is, 100ml of pH 6.5 Fed state simulated intestinal fluid with 20DPM, based on desirability factor 0.5836, achieved from multiple response optimizations. The dissolution results are comparable to percentage of drug absorbed. The regression coefficient (R 2) value of 0.998 and 0.982 demonstrates a very good in vitro/in vivo correlation under post-prandial condition for tamsulosin and dutasteride respectively. Conclusion: The developed method shall be used as a predictive in vitro tool for evaluation of in vivo performance under post-prandial condition.
Aims: This research work was about biorelevant dissolution method development for fluvoxamine extended-release capsule by correlating preprandial and postprandial in vivo performance. Materials and Methods: The mean plasma concentration profile obtained after oral administration of extended-release capsules was deconvoluted using Wagner-Nelson deconvolution technique, to achieve percentage fraction of drug absorbed, and target dissolution profile was derived. Biorelevant dissolution method was developed using USP Apparatus-3, with dissolution media simulating gastrointestinal tract sink condition. A full factorial design of experiment was carried out for optimizing dissolution volume and dips per minutes, to achieve target dissolution profile. Results: The dissolution results observed using office of generic drugs recommend dissolution method were not comparable with target dissolution profile and observed with F 2 value of 37 at preprandial and 43 at postprandial condition. The achieved dissolution profile was comparable with target and observed with F 2 value of 81 at preprandial condition and 85 at postprandial condition. Conclusion: The developed dissolution method establishes good correlation between in vitro drug release and in vivo drug absorption and observed with R 2 value of 0.998 at preprandial condition and 0.997 at postprandial condition. The method gives the advantage of giving biowaiver.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.