Yes / Objectives  In this work we investigated the residual organic solvent content and physicochemical properties of spray-dried chlorothiazide sodium (CTZNa) and potassium (CTZK) salts. Methods  The powders were characterised by thermal, X-ray diffraction, infrared and dynamic vapour sorption (DVS) analyses. Solvent levels were investigated by Karl–Fischer titration and gas chromatography. Key findings  Spray-drying from water, methanol (MeOH) and mixes of MeOH and butyl acetate (BA) resulted in amorphous microparticles. The glass transition temperatures of CTZNa and CTZK were ∼192 and ∼159°C, respectively. These materials retained their amorphous nature when stored at 25°C in dry conditions for at least 6 months with no chemical decomposition observed. DVS determined the critical relative humidity of recrystallisation of CTZNa and CTZK to be 57% RH and 58% RH, respectively. The inlet temperature dependant oxidation of MeOH to formaldehyde was observed; the formaldehyde was seen to deposit within the amorphous matrix of spray-dried product. Spray-drying in the open blowing mode coupled with secondary drying resulted in a three-fold reduction in residual BA (below pharmacopoeial permitted daily exposure limit) compared to spray-drying in the closed mode. Conclusions  Experiments showed that recirculation of recovered drying gas increases the risk of deposition of residual solvents in the spray-dried product. / The Irish Research Council for Science and Engineering Technology (IRCSET), the Solid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under grant number (07/SRC/B1158) and the Irish Drug Delivery Research Network, a Strategic Research Cluster grant (07/SRC/B1154) under the National Development Plan co-funded by EU Structural Funds and Science Foundation Ireland.