Protein Sensitivity to Tungsten - Pharmaceutical Technology

Latest Issue

Latest Issue
PharmTech Europe

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.


1. L.S. Jones, A. Kaufmann, and C.R. Middaugh, J. Pharm. Sci. 94 (4), 918–927 (2005).

2. A.S. Rosenberg, AAPS Journal 8 E501–E507 (2006).

3. W. Liu et al., PDA J. Pharm. Sci. Tech. 64 (1), 11–19 (2010).

4. Y. Jiang et al., J. Pharm. Sci. 98 (12), 4695–4710 (2009).

5. J.S. Bee et al., J. Pharm. Sci. 98 (9), 3290–3301 (2009).

6. M.T. Pope, Heteropoly and Isopoly Oxometalates (Springer-Verlag, New York, 1st ed., 1983).

7. L.S. Jones, A. Kaufmann, and C.R. Middaugh, J. Pharm. Sci. 94 (4), 918–927 (2005).

8. I. Markovic, American Pharmaceutical Review 9 (6), 20–27 (2006).


blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
| Weekly

FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
View Results
Jim Miller Outsourcing Outlook Jim Miller Health Systems Raise the Bar on Reimbursing New Drugs
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerThe Mainstreaming of Continuous Flow API Synthesis
Jill Wechsler Regulatory Watch Jill Wechsler Industry Seeks Clearer Standards for Track and Trace
Siegfried Schmitt Ask the Expert Siegfried SchmittData Integrity
Sandoz Wins Biosimilar Filing Race
NIH Translational Research Partnership Yields Promising Therapy
Clusters set to benefit from improved funding climate but IP rights are even more critical
Supplier Audit Program Marks Progress
FDA, Drug Companies Struggle with Compassionate Use Requests
Source: Pharmaceutical Technology,
Click here