Novel eccentric-pelletisation for rifampicin agglomerates: Process optimization and high-dose pulmonary delivery

High-dose inhaled therapy offers a promising approach for respiratory infections, requiring efficient particle engineering. While fine particles from the milling process improved lung deposition, their poor flowability and high cohesion posed significant challenges for handling and dosing. In this study, a novel eccentric-pelletisation machine was developed to transform purely fine rifampicin powders into spherical agglomerates, significantly improving their flowability, dispersibility, and handling properties. Key manufacturing parameters − including relative humidity (60–70%), eccentric speed (240 rpm), eccentric time (20 min), and sieve size (400 µm) − were systematically optimized using an L₉(3⁴) orthogonal design. The optimized rifampicin agglomerates exhibited favorable properties, including bulk density (∼0.35 g/cm³), flow rate (∼0.59 g/s), roundness (∼0.92), yield (∼89.68%), and fine particle fraction/mass (>55%/5 mg), ensuring efficient high-dose delivery. Furthermore, the optimized agglomerates from three batches demonstrated excellent reproducibility of aerodynamic and physical properties. This study highlights the potential of the eccentric-pellestisation machine as a robust and scalable platform for producing inhalable rifampicin formulations, providing a foundation for industrial production and clinical applications for respiratory infections.