Increase in the specific surface area of budesonide during storage postmicronization.

Abstract

To evaluate an anomalous increase in the specific surface area of budesonide during storage postmicronization. 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. Budesonide exhibited a surface area increase of 22 +/- 2% when stored at 25 degrees C following micronization. The rate of surface area increase was lower at 20 degrees C. 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 approximately 1 microm; and (d) an increase in rugosity/surface roughness. Freshly micronized budesonide exhibited an unusual and significant postmicronization increase in specific surface area upon storage under ambient conditions. Postmicronization stress-relief by intraparticle crack formation, crack propagation with time, and particle fracture seems to be the primary mechanism behind this surface area increase.