Formulation Design and Characterization of Nilotinib Polymeric Nanoparticles by Nanoprecipitation Technique for the Improved Drug Solubility and Dissolution Rate

Nilotinib is a BCS class-IV poorly water-soluble kinase inhibitor drug, that was used for this study to prepare the polymeric nanoparticles by nanoprecipitation technique using Eudragit RL-100 and RS-100 as polymers, Killophore P-188 as a surfactant, and PEG 400 used as a non-volatile, and nontoxic solvent for the improvement of the drug solubility and dissolution rate. The initial process and formulation variables are screened out based on the selected critical quality attributes such as drug release (%), particle size (nm), zeta potential (mV), and polydispersity index. The FT-IR and DSC studies reveal that the drug has no compatibility between the selected drug and the polymers and does not show any additional drug peaks after physical mixing and formulations. The prepared nanoparticles were further characterized to evaluate the particle size (nm), polydispersity index (PDI), zeta potential (mV), entrapment efficiency (%), and in-vitro drug release (%). From the in vitro drug release study, Eudragit RL-100 and Killophore P-188-based formulations showed optimum drug entrapment efficiency with improved drug solubility and dissolution rate in PEG 400 compared to Eudragit RS-100-based formulations. The accelerated stability data for the optimized formulation batch (F6) before and after storage conditions at 40±2 0 C and 75±5% RH indicates that the optimized formulation (F6) is more stable for up to 6 months without changes in drug entrapment efficiency and in vitro dissolution rate. Dissolution kinetic data and diffusion exponent values suggested that optimized formulation followed the Higuchi model with a non-Fickian transport mechanism. According to the results, the preparation method proposed in this study is the most suitable for generating polymeric nanoparticles of nilotinib for improved drug solubility and dissolution rate. The nilotinib-based polymeric nano-formulation proved a potential alternative for better drug release with an enhanced solubility rate.