Abstract: Introduction: Colistin, a cyclic polypeptide linked to a fatty acyl tail, is an old antibiotic with potential toxicity when administered intravenously; however, for treating lung infections, dry powder inhalers (DPIs) have potential to deliver high doses directly to the site of infection. This study has examined the potential to engineer microparticles of colistin, with optimised surface energy, to create particles for effective use in DPIs. Methods: Spray dried colistin sulphate powders were obtained using a Buchi Mini-Spray Drier 190. Inverse Gas Chromatography (IGC) was used to determine the surface energies of the different particles. In vitro dispersion efficiency was measured by aerosolising into a twin stage impinger. Results and Discussion: Spray drying colistin increased the number of inhalable particles (< 6.5 µm) from 23.6% to 78%, providing a substantial improvement in the particle size distribution for delivery to the lower lung.This contributed to the increase in fine particle fraction (FPF) significantly (p< 0.001) from 15 % to 39 % when dispersed from a common commercial device. All spray dried formulations have a significantly higher (p < 0.001) fine particle fraction percentage than colistin as received. IGC surface energy measurements found there is a significantly lower (p < 0.001) total surface energy for all formulations after spray drying when compared to the colistin as received. This was proposed to be due to the peptide's surface active properties. It is further proposed that there is a relationship between the total surface energy and aerosolisation performance, as the total surface energy decreases the FPF increases. Conclusions: This study provides support for the development of an inhalable colistin dry powder formulation engineered via spray drying, that delivers high aerosolisation efficiency from a simple passive inhaler device. The IGC measurement provides evidence to support the surface self-assembly hypothesis for this peptide, that may account for the apparent high FPF.