In this study, lactose crystalline powder was produced to improve its stability. The effect of micronised crystalline lactose on a dry powder inhalation formulation was investigated. Supercritical carbon dioxide (scCO(2)) modified with menthol was used for the conditioning of spray-dried amorphous lactose and salbutamol sulphate to generate micro-spherical crystalline powders. The optimum processing conditions, which include: menthol concentration, temperature and processing time, were determined by experimental design to produce crystalline and a desired particle size. The average particle size of spray-dried amorphous lactose decreased from 8.15 +/- 0.28 mu m to 7.60 +/- 0.10 mu m after conditioning with modified CO2 at 150 bar and 50 degrees C for a period of 5h. The SEM results shows that these particles kept their micro-spherical shape, however, the particle surface became rough due to crystallisation. This particle size reduction was most likely due to increasing surface roughness, which decreased agglomeration between particles. The blend of this fine powder and coarse crystalline lactose enhanced salbutamol sulphate inhalation performance. The emitted fine particle fraction of salbutamol sulphate was enhanced to 40 +/- 0.3% compare to the samples that contained only coarse lactose (38.2 +/- 0.6%) or conditioned lactose (24.6 +/- 0.4%). Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.