(66a) Design of Experiments Study to Formulate Dry Powder Aerosols for Bacterial Biofilm Eradication

Pulmonary bacterial infections are often difficult to eradicate due to the presence of bacterial biofilms, colonies of bacteria protected by their own polysaccharide matrix. Our lab is working to develop combination therapies using a nutrient dispersion compound to entice bacteria out of the biofilm communities and to increase their susceptibility to antibiotics.
The objective of this study was to develop dry powder aerosols containing colistin sulfate (antibiotic), sodium citrate (nutrient dispersion compound), and leucine (to increase flowability) that exhibit high yield, suitable aerodynamic properties, high drug loading, and good antimicrobial properties. Aerosols were generated using a Büchi 190 spray dryer, keeping inlet temperature and pressure drop constant. A two-level central composite design, generated using Minitab® software, was used to vary solution flow rate, atomizer flow rate, leucine concentration, and solution concentration across the sample space. Powders were characterized to determine their yield, water content, chemical composition, and aerodynamic particle size.

Results from this study indicate that various formulation parameters can be tuned to control the yield, water content, and aerodynamic particle size of the spray dried powders. In particular, increasing atomizer flow rate or solution concentration significantly increased powder yield. Powder water content increased with increasing solution concentration or solution flow rate. Aerodynamic particle size, the key parameter that determines deposition of powders in the lungs, was significantly dependent on solution concentration, solution flow rate, and atomizer flow rate. Importantly, spray dried powders were effective in killing 1-day old biofilms of Pseudomonas aeruginosa.