The influence of amino acids on aztreonam spray-dried powders for inhalation

Abstract The dry powder inhalation of antibiotics for the treatment of lung infections has attracted drastically increasing attention as it offers rapid local therapy at lower doses and minimal side effects. In this study, aztreonam (AZT) was used as the model antibiotic and spray-dried to prepare powders for inhalation. Amino acids of glycine (GLY), histidine (HIS) and leucine (LEU) were used as excipients to modify the spray-dried particles. It was demonstrated that the GLY-AZT spray-dried powders formed huge agglomerates with the size of 144.51 µm, which made it very difficult to be delivered to the lungs (FPF: 0.29% w/w only). In comparison with the AZT spray-dried powders, HIS-modified spray-dried powders showed increased compressibility, indicating larger distance and less cohesion between particles; while the LEU-modified spray-dried particles showed a hollow structure with significantly decreased densities. The fine particle fraction for HIS- and LEU-modified powders was 51.4% w/w and 61.7% w/w, respectively, and both were significantly increased (one-way ANOVA, Duncan's test, P  0.05) compared to that of AZT spray-dried powders (45.4% w/w), showing a great potential to be applied in clinic.