Development and Validation of a QbD-Based Stability indicating UV Spectrophotometric Method for Simultaneous Estimation of Lenvatinib and Palbociclib in Bulk and Formulation with Greenness Assessment

Abstract

The present study aimed to develop and validate a simple, environmentally sustainable, stability-indicating UV spectrophotometric method for simultaneous estimation of lenvatinib (LEN) and palbociclib (PAL) in bulk drugs and liposomal formulations. An Analytical Quality by Design approach using Central Composite Design was employed to optimize the analytical conditions. A methanol mixture (50:50, v/v) was selected as the optimum solvent. LEN and PAL showed maximum absorbance at 243 and 220 nm, respectively, with a common isosbestic point at 256 nm. The method was validated according to ICH Q2(R2) guidelines. Both drugs exhibited linearity over 2–10 µg/mL, with correlation coefficients above 0.99. Recovery values were close to 100%, while precision, ruggedness, robustness and repeatability studies showed %RSD values below 2%. The method demonstrated adequate sensitivity, with LOD/LOQ values of 0.48/1.46 µg/mL for LEN and 0.22/0.683 µg/mL for PAL. Forced degradation studies confirmed its stability-indicating capability under acidic, alkaline, oxidative, thermal and photolytic conditions. Greenness assessment using AGREE, AGREEprep, ComplexGAPI and BAGI indicated favorable environmental performance. The developed method is simple, economical, reliable and suitable for routine quality control and stability assessment of LEN and PAL formulations.