Enhancing Rifampicin Solubility: Development and Evaluation of Biodegradable Chitosan Nanosuspensions

Tuberculosis is the leading cause of mortality from infectious diseases worldwide, with rifampicin as a first-line drug. However, its poor solubility and inconsistent bioavailability limit therapeutic outcomes and contribute to drug resistance. This study aimed to enhance rifampicin solubility and delivery using chitosan-based nanosuspensions. Rifampicin-loaded nanosuspensions were prepared by the ionic gelation method employing chitosan as a biodegradable polymer and Pluronic F68, Tween 80 and Span 60 as stabilizers. The formulations were evaluated for drug entrapment efficiency, particle size, Polydispersity Index (PDI), zeta potential, morphology (SEM), in-vitro drug release, kinetic modeling and stability. Entrapment efficiency ranged from 75.7% to 89.3%, with Pluronic F68 formulations showing the highest values. The optimized batch (F24) demonstrated a mean particle size of 120.08 nm, PDI of 0.110 and zeta potential of +48.49 mV, indicating good stability. SEM confirmed spherical, nonagglomerated particles. The optimized nanosuspension achieved a sustained drug release of 87.17% over 12 h and followed zero-order and Korsmeyer–Peppas kinetics. Stability studies revealed consistent performance under refrigerated storage for 60 days. Chitosan-based nanosuspensions significantly improved rifampicin solubility, stability and release profile. The optimized formulation offers a promising approach to overcome bioavailability limitations of rifampicin and may enhance therapeutic efficacy in tuberculosis management. This strategy can potentially be extended to other poorly soluble drugs.