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Effect of initial buffer composition on pH changes during far-from-equilibrium freezing of sodium phosphate buffer
G Gómez1, M J Pikal, N Rodríguez-Hornedo
1Dupont Pharmaceuticals, Manatí, Puerto Rico.
Pharmaceutical Research
|May 5, 2001
Summary
Freezing sodium phosphate buffers causes pH shifts due to salt precipitation. Lowering initial pH and concentration increases final pH, crucial for pharmaceutical applications.
Area of Science:
- Physical Chemistry
- Biochemistry
- Materials Science
Background:
- Understanding pH stability is critical for pharmaceutical formulations.
- Far-from-equilibrium processes like freezing can induce significant chemical changes.
- Salt precipitation during freezing impacts solution properties.
Purpose of the Study:
- To investigate pH changes during non-equilibrium freezing of sodium phosphate buffers.
- To correlate pH shifts with buffer composition (concentration, initial pH).
- To assess relevance for pharmaceutical applications involving large sample volumes and supersaturation.
Main Methods:
- Prepared sodium phosphate buffers (8-100 mM, pH 5.7-7.4).
- Monitored temperature and pH in situ during cooling to -10°C.
- Confirmed salt crystallization (Na2HPO4·12H2O) via ion analysis and X-ray diffraction.
Main Results:
- Ice crystallization triggered abrupt pH decreases due to Na2HPO4·12H2O precipitation.
- Lower initial buffer concentrations and pH led to higher final pH values at -10°C.
- Example: Initial pH 7.4 buffers showed final pH 4.2 (50-100 mM) to 5.2 (8 mM).
Conclusions:
- Precipitation-induced pH shifts depend on initial pH, salt concentration, and ion activity.
- The ion activity product is a key parameter for describing salt precipitation in mixed-salt solutions.