Protein Sensitivity to Tungsten - Pharmaceutical Technology

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Protein Sensitivity to Tungsten
The authors investigate the effect of low pH and ionic strength on aggregation using turbidity measurements and size-exclusion–high-performance liquid chromatography.

Pharmaceutical Technology
pp. s28-s32


Assays based on turbidity and SEC can be used to evaluate protein sensitivity to tungsten in order to optimize formulations for the packaging of biologics in glass prefilled syringes. Ionic strength and pH are important elements in the aggregation of proteins by tungstate polyoxyanions. An acidic pH is necessary for the generation of tungstate polyoxyanions and aggregation may be blocked by increasing the ionic strength of the formulation. This suggests that the interaction of polyoxometalates with proteins is primarily electrostatic. Some proteins precipitate with tungstate more readily than others, but a net positive charge is essential. Although protein size does not appear to be important, other factors related to a protein's structure may play a role in determining binding and aggregation by tungstate polyoxyanions. Syringes made of plastic, which are free of both silicone oil and tungsten, should be considered for use with sensitive biomolecules.

Vinod Vilivalam*, PhD, is director of strategic market and technical development, Lloyd Waxman is a principal scientist, West Analytical Labs, Tadd Steeley is a senior chemist, all at West Pharmaceutical Services, 101 Gordon Drive, Lionville, PA 1934, tel: 610.594.3147,

*To whom all correspondence should be addressed.


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