Formulation and Optimization of Pyrazinamide-Loaded Solid Lipid Nanoparticles by Employing a Design of Experiments Approach.

Objectives: Tuberculosis (TB) remains a major worldwide health challenge causing morbidity and mortality, necessitating novel approaches for its effective therapy. Pyrazinamide (PYZ), a nicotinamide analogue, is a key frontline drug significantly involved in the treatment of TB. However, its dose-dependent hepatotoxicity is a major concern that needs to be addressed. The aim of the current research was to develop PYZ-loaded solid lipid nanoparticles (PYZ-SLNs) as a potential therapeutic intervention for treating TB. Materials and Methods: The PYZ-SLNs were formulated by a high-pressure homogenization technique and optimized using a 23-factorial design. The drug concentration, emulsifier concentration, and homogenization cycles were considered critical formulation and processing parameters to study their effects on essential attributes of quality of PYZ-SLNs, i.e., entrapment efficiency (EE%), drug loading (DL%), and particle size. Results: The optimized PYZ-SLNs showed a particle size of 401±08 nm, EE% of 86.24±1.15, DL% of 14.38±0.85. The Conclusion: PYZ-SLNs could be a promising carrier for the treatment of TB via the oral intestinal lymphatic pathway, circumventing its hepatic first-pass metabolism and thereby preventing hepatic adverse effects.