A ROBUST METHOD FOR SIMULTANEOUS QUANTITATIVE DETERMINATION OF EPLERENONE POLYMORPHS IN TABLET FORMULATION BY X-RAY POWDER DIFFRACTION

摘要

Objective: Eplerenone (EPL) is a selective aldosterone blocker used for the treatment of cardiovascular disease. It is known from the literature that the Polymorphs of EPL, form-H and form-L exist thermodynamically enantiotropic in relation, and encompass noticeably different dissolution rates in aqueous media. In view of increasing regulatory concern and bio-pharmaceutical performance, having an accurate method to quantitatively eva-luate the solid phase(s) of the drug substance in drug product is reasonably vital. The aim of this work is to develop and validate an accurate, pre-cise, rapid and robust method for simultaneous quantitative determination of EPL polymorphs in tablets formulation by X-Ray Powder Diffraction. Me thods: Geometric mixtures were prepared by taking varying amounts of form-H and from-L, while keeping placebo amount fixed. These spiked samples were scanned using X-Ray Powder Diffractometer and the method was validated. Robustness of the method was tested against intensity variation, scan time variation and specimen holder type. Results: Validation results of the method demonstrated acceptable correlation (R20.9991) between actual and predicted values, acceptable accu-racy (recovery from 88% to 102%) and precision with an RSD less than 1.0%. Additionally, the method was tested for robustness, and found to be very robust to the effects caused by the plausible variations in X-ray intensity, scan time and sample quantity. Conclusion: The method can readily be used by any quality control laboratory as a control measure for Eplerenone polymorphs composition in tablets so as to ensure the quality and efficacy