IMPLEMENTATION OF QUALITY BY DESIGN APPROACH TO DEVELOP AND VALIDATE STABILITY INDICATING ASSAY METHOD FOR SIMULTANEOUS ESTIMATION OF SOFOSBUVIR AND LEDIPASVIR IN BULK DRUGS AND TABLET FORMULATION

This study developed a stability-indicating reversed-phase high-performance liquid chromatography method for simultaneous estimation of sofosbuvir and ledipasvir of bulk drug and formulation by using a QbD approach. Literature survey reveals that there were very few analytical methods available for the simultaneous estimation of sofosbuvir and ledipasvir. An attempt was made to develop and validate stability indicating assay method using RP-HPLC through QbD approach. In a QbD approach, Box-Behnken screening based on critical method parameters, i.e. (Buffer pH, organic phase-% methanol and flow rate). The interaction effect of these parameters on the response variables (Retention Time, NTP and tailing factor) were evaluated through 3D response graphs. The plots revealed the final chromatographic conditions of the method. The chromatographic separation was achieved using C18 inertsil ODS-2, 250 mm × 4.6 mm × 5µ column, buffer ammonium acetate and PDA detector at 254 nm. The developed method was successfully applied for the determination of the two drugs from its pharmaceutical formulation as well as successfully applied for forced degradation studies. Force degradation studies include acid hydrolysis, base hydrolysis, oxidation, thermal degradation and photolytic degradation of sofosbuvir and ledipasvir in combination. The methods can be used for routine analysis of formulations containing any of the above drugs or combinations without any alteration in the chromatographic conditions.