Pulmonary delivery of pyrazinamide-loaded large porous particles.

摘要: We have improved the aerodynamic properties of pyrazinamide loaded large porous particles (PZA-LPPs) designed for pulmonary delivery. To overcome segregation different components occurring during spray drying process and to obtain homogeneous LPPs, parameters were modified decrease speed. As a result, good lung delivery obtained with fine particle fraction (FPF) 40.1±1.0%, an alveolar (AF) 29.6±3.1%, mass median diameter (MMADaer) 4.1±0.2μm geometric standard deviation (GSD) 2.16±0.16. Plasma epithelial lining fluid (ELF) concentrations evaluated after intratracheal insufflation PZA-LPPs (4.22mgkg(-1)) into rats compared intravenous administration (iv) solution (5.82mgkg(-1)). The in vivo pharmacokinetic evaluation reveals that leads rapid absorption plasma absolute bioavailability 66%. This proves dissolve fast upon deposition PZA crosses efficiently barrier reach systemic circulation. 1.28-fold higher ELF than iv ratio over was 2-fold greater. Although these improvements are moderate, appears interesting alternative oral molecule should now be tested infected animal model evaluate its efficacy against Mycobacterium tuberculosis.