Increase in the specific surface area of budesonide during storage postmicronization

Purpose. To evaluate an anomalous increase in the specific surface area of budesonide during storage postmicronization. Methods. Budesonide was micronized using a conventional air-jet mill. Surface areas and total pore volumes were measured using nitrogen sorption. Porosity was measured using mercury intrusion porosimetry. Particle size was measured using laser diffraction. Results. Budesonide exhibited a surface area increase of 22 +/- 2% when stored at 2,5degreesC following micronization. The rate of surface area increase was lower at 20degreesC, suggesting a temperature-dependent stress relaxation mechanism for the micronized particles. The increase in surface area was accompanied by: (a) an increase in total pore volume; (b) a shift of the pore size distribution to smaller pore sizes; (c) a decrease in size of particles above similar to1 mum; and (d) an increase in rugosity/surface roughness. Conclusions. Freshly micronized budesonide exhibited an unusual and significant postmicronization increase in specific surface area upon storage under ambient conditions. Post micronization stress-relief by intraparticle crack formation, crack propagation with time, and particle fracture seems to be the primary mechanism behind this surface area increase.