Integrating Risk Assessment and Design of Experiments for the Rational Design of Albumin-Based Nanoparticles

Background: Ibudilast is a promising therapeutic agent, but its poor oral bioavailability limits its clinical efficacy. Nanoparticle-based drug delivery systems, especially those utilizing albumin as a carrier, offer a potential strategy to enhance drug solubility, stability, and controlled release. However, nanoparticle formulation is influenced by various product and process parameters, which can lead to inconsistency in quality. To overcome these challenges, a Quality by Design (QbD) approach was employed to systematically optimize formulation variables and ensure the robust development of nanoparticles. Methods: A thorough risk assessment was performed to define the Quality Target Product Profile (QTPP) and identify critical material attributes and process parameters. A D-optimal experimental design was used to optimize the concentrations of albumin and ibudilast. The prepared nanoparticles were evaluated for key physicochemical parameters, including particle size, polydispersity index (PDI), entrapment efficiency (EE%), zeta potential, and drug release behavior. Results: The optimized formulation (O1) exhibited a particle size of 185.23 nm, a PDI of 0.264, indicating uniform distribution, and an entrapment efficiency of 78.02 %. The zeta potential of −22.9 mV suggested good colloidal stability. Furthermore, the optimized nanoparticles demonstrated an extended-release profile compared to free ibudilast, indicating improved drug delivery potential. Conclusion: This study successfully demonstrates the application of the QbD framework in developing albumin-based ibudilast nanoparticles with improved encapsulation and release characteristics. The findings support the potential of this delivery system to enhance therapeutic outcomes for poorly bioavailable drugs, such as ibudilast.