Monitoring ceramic hydroxyapatite media degradation using dynamic image analysis and uniaxial confined bulk compression.
Ceramic hydroxyapatite (CHT) is a multimodal chromatographic medium widely used in the pharmaceutical industry for the purification of biomolecules. CHT is a sintered form of hydroxyapatite crystals with moderate stability at acidic conditions. This moderate stability may lead to underperformance of CHT packed bed lifetime, especially under acidic conditions, which should be monitored by diagnostic tools to design optimal buffer systems for the step. This study presents the application of dynamic image analysis (DIA) and uniaxial confined bulk compression (UCBC) to monitor CHT particle degradation as a function of buffer composition. DIA was used to evaluate changes in solidity and morphology, while UCBC was used to evaluate changes in resistance to uniaxial compression. All properties were studied as a function of bed position and operational parameters. Results show that when CHT is exposed to acidic pH, adding phosphate and/or calcium at concentrations of 1 mM minimizes changes in particle solidity and mechanical strength. Changes in CHT morphological properties (i.e., convexity, aspect ratio) are also affected by the presence of calcium and/or phosphate in the inlet buffers. Furthermore, calcium and phosphate have a positive effect on the mechanical behavior of CHT, which is related to changes in the CHT particle solidity.
Purification Process Development, Amgen Inc., Thousand Oaks, CA 91320, USA. oliverk@amgen.com
Oliver
O
Kaltenbrunner
Shawn
S
Cao
Esteban
E
Freydell
Nick
N
Keener
Li
L
Zhu
Nancy
N
Jiao
Brian
B
Williamson
Mark A
MA
Snyder
Larry J
LJ
Cummings
D002516:Ceramics / Q000737:chemistry*; D002845:Chromatography / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D017886:Durapatite / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007091:Image Processing, Computer-Assisted / Q000295:instrumentation / Q000379:methods*; D010316:Particle Size; D013314:Stress, Mechanical
D017886:Durapatite