Electrostatic charge and aerodynamic size distributions analysis were performed using an Electrical-Single Particle Aerodynamic Relaxation Time (E-SPART) Analyzer in formulation screening of dry powders for use in aerosol delivery to the lung. The respirable fraction (RF) of drugs delivered by dry powder inhalers (DPIs) can be improved more effectively by using hydrophobic microspheres as carriers. Poly (D,L-lactide-co-glycolide) microspheres (PLGA) prepared in the respirable size range (3-7 mu m) were treated with polyamino acids and isopropanol in order to obtain particles of surface charge suitable for use in DPIs. The powder formulations were evaluated for their degree of aggregation by cascade impaction following delivery by the Pfeiffer(R) DPI. The IPA treated PLGA microspheres had a significantly higher RF (12.9%) as compared to the PL and PGA treated microspheres (3.3 and 2.4%, respectively), and untreated microspheres (3.8%). Results of electrostatic charge determined by E-SPART analysis suggested that the higher RF for the IPA formulation may be due to its inter-particle repulsive forces caused by the unipolar charge (+56.3 mu C/g) distribution of the powder.