Quality by Design-Driven Development of Hydroxyurea-Loaded Polymeric Nanoparticles

The proposed research aimed to study the hydroxyurea-laden polycaprolactone nanoparticulate formulation (HxU-loaded PCL NPs). The nanoparticles were optimized by employing the “Quality by Design” approach with Design Expert software (version 9.0). After setting Quality Target Product Profile (QTPP), different compositional and process parameters were selected that could have a significant impact on response variables, viz., particle size, polydispersity index (PDI), and % entrapment efficiency. The Box-Behnken design was selected as a suitable design for optimization purposes as it gives higher-order response surfaces and requires less number of runs compared to normal factorial design. Optimized HxU-loaded PCL NPs were then validated and further characterized for morphology, in vitro release, and stability testing as per ICH guidelines. The HxU-loaded PCL NPs were successfully formulated by employing the QbD approach (BBD design) after assessing the influence of process and formulation variables on critical quality attributes. The optimized batch of NPs had a particle size of 234.13 ± 0.99 nm, PDI of 0.08 ± 0.03, and 77.38 ± 1.10% entrapment efficiency. Morphological analysis through scanning electron microscopy (SEM) demonstrated NPs to be spherical and uniform. In vitro release at pH 6.8 simulated salivary solution demonstrated sustained release of hydroxyurea from polycaprolactone nanoparticles.