PROCESS-INDUCED CRYSTALLINITY CHANGES IN ALBUTEROL SULFATE AND ITS EFFECT ON POWDER PHYSICAL STABILITY

Pharmaceutical powders are often milled to achieve the optimum particl e size. These size reduction processes can introduce dislocations and/ or defects onto particle surfaces affecting the overall crystallinity of the powder. If enough energy is imparted, amorphous regions on the particle surfaces may be produced. These amorphous regions have the pr opensity to absorb significant quantities of water. In this study the effect of sorbed water on the physical characteristics of albuterol su lfate is investigated. Physical properties of this compound are studie d in both micronized and unmicronized states using scanning electron m icroscopy, differential scanning calorimetry, powder x-ray diffraction , solution microcalorimetry, laser diffraction particle size analysis and water vapor sorption analysis. Subtle differences in crystallinity induced by air jet micronization are detected by several analytical m ethods. Amorphous to crystalline conversions are observed, the kinetic s of which are found to be both temperature and relative humidity depe ndent. These experiments show the dynamic nature of micronized albuter ol sulfate and aid in the determination of the actual physical state o f this pharmaceutical powder.