title: Increase in the specific surface area of budesonide during storage postmicronization.
abstract: OBJECTIVE
  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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dura Pharmaceuticals, San Diego, California 92121, USA. vidya_joshi@hotmail.com
authors.forename: Vidya
authors.initials: V
authors.lastname: Joshi
authors.forename: Sarvajna
authors.initials: S
authors.lastname: Dwivedi
authors.forename: Gary H
authors.initials: GH
authors.lastname: Ward
mesh_terms: D000327:Adsorption; D019819:Budesonide / Q000737:chemistry*; D004356:Drug Storage; D008628:Mercury / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry; D010316:Particle Size; D016062:Porosity; D011208:Powders; D013499:Surface Properties; D013997:Time Factors
chemical_list: D011208:Powders; D019819:Budesonide; D008628:Mercury; D009584:Nitrogen