Development of high-dose carrier-free inhalable heparin sodium microparticles using co-jet-milling technology

Pulmonary drug delivery represents a non-invasive and efficient alternative to traditional routes of administration, with benefits including enhanced absorption and better patient adherence. This study focuses on the design of inhalable heparin sodium (HS) particles tailored for managing pulmonary infectious diseases and associated complications like pulmonary thromboembolism. A carrier-free dry powder formulation has been developed using co-jet-milling technique, utilizing magnesium stearate (MgSt) as an excipient to optimize particle properties. MgSt demonstrated the ability to modify particle characteristics, enhance aerosolization performance, and improve formulation stability. Experimental results showed that co-milling with MgSt significantly improved the emitted rate (ER) and emitted fine particle fraction (E-FPF) and stability of the formulation. These findings underscore MgSt's dual functionality in stabilizing and enhancing the aerosolization performance of carrier-free HS formulations for dry powder inhalers (DPIs), presenting an approach for high-dose carrier-free DPI formulation design.