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The aim of this study was to improve the aerosolisation behaviour of disodium cromogycate (DSCG), using spray drying technique. The effect of vehicle on the drug particle properties was investigated. l-leucine was selected as a natural antiadherent amino acid to improve the deagglomeration of DSCG particles. Spray dried samples of DSCG alone or with l-leucine were prepared from water and ethanol under the same conditions. The powder properties of the samples were examined by laser diffraction, helium densitometer, X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. The in vitro deposition was determined, using an Andersen cascade impactor with a Spinhaler® at a flow rate of 60 l/min. An amorphous form of the drug was obtained when water was used. However, crystal transformation of original DSCG in the presence of ethanol during spray drying resulted in production of elongated particles. These particles exhibited improved aerodynamic properties, compared to the amorphous and commercial materials. Significant differences in fine particle fraction were observed using the two vehicles. Co-spray drying of DSCG and l-leucine improved the deposition profiles of the drug. These results indicated that the change in crystal structure of DSCG during spray drying process was susceptible to the nature of the vehicle. A crystalline form of DSCG with good aerodynamic properties was achieved during spray drying process. In addition, the processing of DSCG with l-leucine in a single step using ethanol resulted in an improvement in dispersion properties of the drug particles.