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

• Published in: Journal of pharmacy and pharmacology 2012-11, Vol.64 (11), p.1570-1582
• Main Authors: Paluch, Krzysztof J., Tajber, Lidia, Corrigan, Owen I., Healy, Anne Marie
• Format: Article
• Language: English
• Subjects: amorphous; Chemistry, Pharmaceutical - methods; Chlorothiazide - chemistry; Helium - chemistry; Microscopy, Electron, Scanning; Microspheres; morphology; nanoporous microparticles; Porosity; Salts; Solvents - chemistry; specific surface area; spray drying; Surface Properties
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/j.2042-7158.2012.01539.x

Objectives  This work investigated the impact of spray drying variables such as feed concentration, solvent composition and the drying mode, on the micromeritic properties of chlorothiazide sodium (CTZNa) and chlorothiazide potassium (CTZK). Methods  Microparticles were prepared by spray drying and characterised using thermal analysis, helium pycnometry, laser diffraction, specific surface area analysis and scanning electron microscopy. Key findings  Microparticles produced under different process conditions presented several types of morphology. To systematise the description of morphology of microparticles, a novel morphology classification system was introduced. The shape of the microparticles was described as spherical (1) or irregular (2) and the surface was classified as smooth (A) or crumpled (B). Three classes of morphology of microparticles were discerned visually: class I, non‐porous; classes II and III, comprising differing types of porosity characteristics. The interior was categorised as solid/continuous (α), hollow (β), unknown (γ) and hollow with microparticulate content (δ). Nanoporous microparticles of CTZNa and CTZK, produced without recirculation of the drying gas, had the largest specific surface area of 72.3 and 90.2 m2/g, respectively, and presented morphology of class 1BIIIα. Conclusions  Alteration of spray drying process variables, particularly solvent composition and feed concentration can have a significant effect on the morphology of spray dried microparticulate products. Morphology of spray dried particles may be usefully described using the morphology classification system.