Impact of process variables on the micromeritic and physicochemical properties of spray-dried porous microparticles, part I: introduction of a new morphology classification system

YesObjectives This work investigated the impact of spray drying variables such as feedconcentration, solvent composition and the drying mode, on the micromeriticproperties of chlorothiazide sodium (CTZNa) and chlorothiazide potassium(CTZK).Methods Microparticles were prepared by spray drying and characterised usingthermal analysis, helium pycnometry, laser diffraction, specific surface area analysisand scanning electron microscopy.Key findings Microparticles produced under different process conditions pre-sented several types of morphology.To systematise the description of morphology ofmicroparticles, a novel morphology classification system was introduced. The shapeof the microparticles was described as spherical (1) or irregular (2) and the surfacewas classified as smooth (A) or crumpled (B). Three classes of morphology of micro-particles were discerned visually: class I, non-porous; classes II and III, comprisingdiffering types of porosity characteristics. The interior was categorised as solid/continuous (a), hollow (b), unknown (g) and hollow with microparticulate content(d). Nanoporous microparticles of CTZNa and CTZK, produced without recircula-tion of the drying gas, had the largest specific surface area of 72.3 and 90.2 m2/g,respectively, and presented morphology of class 1BIIIa.Conclusions Alteration of spray drying process variables, particularly solvent com-position and feed concentration can have a significant effect on the morphology ofspray dried microparticulate products. Morphology of spray dried particles may beusefully described using the morphology classification system.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

Impact of process variables on the micromeritic and physicochemical properties of spray-dried microparticles, part II: physicochemical characterisation of spray-dried materials

YesObjectives  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