Abstract
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°C following micronization. The rate of surface area increase was lower at 20°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 ∼1 μm; 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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Joshi, V., Dwivedi, S. & Ward, G.H. Increase in the Specific Surface Area of Budesonide During Storage Postmicronization. Pharm Res 19, 7–12 (2002). https://doi.org/10.1023/A:1013690929173
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DOI: https://doi.org/10.1023/A:1013690929173