APPLICATION OF QUALITY BY DESIGN IN RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR EFAVIRENZ IN BULK AND TABLET DOSAGE FORM

Abstract

Objective: This study focused on designing and validating a reliable and efficient Quality by Design assisted RP-HPLC analytical procedure for efavirenz in bulk and tablet dosage form. Methods: The significant analytical variables (CMPs) were optimized by using Central Composite Design, analytical variables; including solvent ratio composition and chromatographic flow condition, to achieve the desired Critical Quality Attributes (CQAs). Chromatographic resolution was achieved using a C18 stationary phase under finalized experimental settings. Subsequently, validation of the analytical procedure was performed according to ICH recommendations; covering specificity, linear response, recovery, repeatability, robustness, reproducibility, detection limit and quantification capability. Results: The finalized chromatographic procedure generated efficient peak separation with a retention period near 3.75 minutes. Excellent calibration behavior was observed across the concentration interval of 5-25 µg/ml, with a strong regression value (R2 = 0.9999). Recovery analysis verified the accuracy of the developed procedure (98-102 %), while precision was satisfactory, with %RSD < 2.0. Acceptable sensitivity characteristics were exhibited by the analytical technique, with LOD of 0.0098 µg/ml and LOQ of 0.0297 µg/ml. Minor intentional modifications; mobile phase composition and detection wavelength introduced during robustness evaluation produced no meaningful influence on analytical performance (%RSD = 0.01-0.03%), while ruggedness studies also confirmed reproducibility across analysts (%RSD = 0.03%). Evaluation of the commercial tablet dosage form (EFAVIR), resulted in an assay value of 99.43%. Conclusion:The developed QbD-assisted RP-HPLC technique was stable, accurate and appropriate for regular quantitative determination of efavirenz in bulk drug and tablet dosage forms.