Inhalable Chitosan Microparticles: A Spray-Drying Approach for Enhanced Pulmonary Delivery of Rifampicin

The study aimed to produce spray-dried microparticles with a higher payload of rifampicin and a suitable size range for targeted drug delivery to alveolar macrophages. The microparticles were initially optimized with respect to solution feed rate, concentration of chitosan, and addition of surfactant, followed by homogenization. The optimized formulations were loaded with rifampicin in the ratios of 1:1 (F4L), 1:2 (F3L and F5L), and 1:4 (F2L), respectively. The microparticles were assessed for their particle size, morphology, drug content, flow properties, drug release, and aerodynamic performance. The chemical compatibility of the drug with excipients in microparticles was assessed using FTIR, while the crystalline and/or amorphous nature of the spray-dried powder was confirmed using XRD analysis. The pharmacokinetic parameters were compared after oral and intratracheal administration in rats. The microparticles, within the size range of 2 to 6 μm and percentage yield of 23-51%, were efficiently synthesized. The structure of the microparticles was significantly altered with increasing concentrations of rifampicin in the microparticles. The microparticles had a drug association efficiency of above 60%. The microparticles released rifampicin in a sustained fashion (>95%) by anomalous non-Fickian diffusion. The optimized microparticles (F5L) achieved a dispersed fraction of 89%, an inhaled fraction of 69% with FPF_{≤3 μm} of 51.51%. The microparticles achieved a significantly lower area under the curve (AUC) of 80.845 ± 9.42 μg/mL·h than marketed tablets (140.468 ± 12.53 μg/mL·h) due to higher lung drug retention. The <i>in vitro</i> and <i>in vivo</i> findings indicate the suitability of microparticles for potential applications in tuberculosis.