Impact of process variables on the micromeritic and physicochemical properties of spray-dried microparticles - Part II. Physicochemical characterisation of spray-dried materials

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.