Respirable nanoparticle agglomerates of ibuprofen were produced by wet milling and spray drying. The impact of formulation factors on the yield and performance of the powders was studied using a 23 full factorial design. The nanoparticle agglomerates were crystalline and exhibited enhanced dissolution profiles. The stabilizer used for the formation of the nanosuspensions can affect the yield and size of nanoparticle agglomerates. Mannitol and leucine are useful excipients for the spray drying of nanosuspensions to produce respirable particles.