Analytical Quality by Design-Based RP-HPLC Method for the Quantification and Stability Assessment of Nilotinib in Bulk and Nanoformulations

Abstract

Background: Nilotinib, a tyrosine kinase inhibitor of the second generation, is susceptible to stress-induced degradation that could undermine therapeutic effectiveness.Materials and Methods: The accelerated stability studies have been performed on both bulk Nilotinib as well as its nanoformulation in an acidic, basic, oxidative, thermal, and photolytic environment following ICH-recommended guidelines. The developed RP-HPLC method showed efficient separation of Nilotinib from its degraded products and thus is proven to be an appropriate stability-indicating analytical method for the analysis of Nilotinib and its nanoformulation. Supporting Fourier-Transform Infrared Spectroscopy (FTIR) analysis offered molecular-level proof of these changes.Results: Degradation processes included amide hydrolysis, dealkylation, oxidative N-oxide formation, thermal rearrangement, and photolytic radical-mediated cleavage. In all conditions of stress, the nanoformulation uniformly showed diminished degradation than the bulk drug, which emphasizes the shielding effect of the carrier matrix.Conclusion: In combination, HPLC and FTIR profiling created a complete degradation map of Nilotinib, highlighting the nanoformulation's improved stability and corroborating its viability for enhanced therapeutic dependability.

Keywords: Analytical Quality by Design (AQbD); Box-Behnken Design; Nilotinib; Pharmaceutical Analysis; RP-HPLC; Stability-Indicating Method