Increase in the specific surface area of budesonide during storage postmicronization
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Published on: December 23, 2016
Vidya Joshi1, Sarvajna Dwivedi, Gary H Ward
1Dura Pharmaceuticals, San Diego, California 92121, USA. vidya_joshi@hotmail.com
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 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.
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