Electrosprayed co-crystals of levofloxacin for inhalation: a strategy for excipient-free dry powder antibiotics

Pulmonary delivery of antibiotics provides a targeted means of treating lower respiratory tract infections, yet the development of dry powder inhaler (DPI) formulations is limited by the poor aqueous solubility and physical instability of many active pharmaceutical ingredients. Here, we report a dual-platform strategy that combines mechanochemical co-crystallisation and electrospraying to produce, for the first time, an excipient-free inhalable formulation of levofloxacin (LEV). Three GRAS-listed co-formers-fumaric acid, salicylic acid, and isonicotinic acid-were screened using liquid-assisted grinding. Co-crystals of LEV with salicylic acid (SA) and isonicotinic acid (IN) were identified as crystalline, thermally stable, and physically robust. These co-crystals were processed via cone-jet electrospraying, yielding uniform, spherical microparticles with aerodynamic diameters below 5 µm, suitable for deep-lung deposition. Powder X-ray diffraction and microscopy confirmed that co-crystal integrity and morphology were preserved throughout electrospraying. This work establishes a scalable, low-temperature manufacturing platform for producing high-performance, excipient-free inhalable antibiotics. Beyond levofloxacin, this approach provides a general framework for on-demand, personalised pulmonary drug delivery, bridging solid-state chemistry with advanced particle engineering.