Spray-Dried Carrier-Free Dry Powder Tobramycin Formulations With Improved Dispersion Properties

Tobramycin was spray dried at different temperatures from different water to isopropanol feed ratios (0:100-20:80) in order to obtain dry powder formulations for inhalation. The spray-dried powders were characterized for their physicochemical properties including crystallinity, morphology, density, water content, and particle size distribution using X-ray powder diffraction, scanning electron microscopy, tapped density measurements and laser diffraction. Aerosol performance was studied by dispersing the powders into a Multi-Stage Liquid Impinger with an Aerolizer (R) device. The results indicate that formulations spray dried at temperatures below 200 degrees C exhibited poor powder flow properties and were therefore unlikely to display optimal aerosolisation characteristics. Nevertheless, it is interesting to note that the presence of water in the suspensions used for spray-drying markedly enhanced the fine particle fraction, which was about 37% for the raw tobramycin and about 57% for a powder obtained from a suspension containing 2% (v/v) water. Overall, this latter formulation was shown to keep its initial particle size distribution and aerodynamic behaviour for 12 months of storage at 40 degrees C and 75% RH. These new carrier-free formulations provide an attractive alternative for delivering high doses of antibiotics directly to the site of infection while minimising systemic distribution. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1463-1475, 2009