Abstract

IMPLEMENTATION OF QbD APPROACH TO THE RP-HPLC METHOD DEVELOPMENT AND VALIDATION OF ROFLUMILAST IN BULK AND TABLET DOSAGE FORM: AN APPLICATION IN DEGRADATION STUDY

Arpit D. Shah*, Dr. Chhaganbhai N. Patel

ABSTRACT

Quality by Design (QbD) is a philosophy that refines the level of knowledge associate with a product that use process understanding to deliver a product with the desired critical quality attributes. The objective of this present study was to develop and demonstrate an integrated multivariate QbD approach to develop and quantify the constitute concentration of Roflumilast drug in bulk and tablet dosage form. To facilitate studies investigating the determination of Roflumilast, RP-HPLC method was developed and validated according to ICH Q2 guideline and application of this method to different stress condition of Roflumilast. The developed method employed mobile phase Acetonitrile and Potassium Dihydrogen phosphate buffer (pH 6) (65:35, v/v) and flow rate 1.0 ml/min which was optimized with help of design expert software. Method was developed using column C18 ACE (150 mm x 4.6 mm, 5μm) and detection wavelength at 250nm. The retention time was 5.34 min. High linearity of the developed method was confirmed over concentration range of 20 – 50 μg/mL and correlation coefficient of 0.9989. The percentage RSD for precision and accuracy of the method was found to be less than 2%. The drug was subjected to acidic, alkali, neutral, oxidative, heat and photo degradation stress. All the peaks of degradation product separate were well resolved from the standard drug peak with significant Relative retention time. Drug shows significantly degraded in acidic and alkali condition while remain stable in other conditions

Keywords: Roflumilast (RFL), Quality by Design (QbD), Design expert optimization, RPHPLC, Degradation study, Validation