Ionic strength affects tertiary structure and aggregation propensity of a monoclonal antibody adsorbed to silicone oil–water interfaces. Issue 2 (4th December 2012)

• Record Type: Journal Article
• Authors: Gerhardt, Alana; Bonam, Kurt; Bee, Jared S.; Carpenter, John F.; Randolph, Theodore W.
• Is Part Of: Journal of pharmaceutical sciences. Volume 102:Issue 2(2013:Feb.)
• Page Start: 429
• Page End: 440
• Publication Date: 2012-12-04
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.23408
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Therapeutic proteins formulated in prefilled syringes lubricated with silicone oil come in contact with silicone oil–water interfaces for their entire shelf lives. Thus, the interactions between protein and silicone oil were studied to determine the effect of silicone oil on a monoclonal antibody's stability, both at the interface and in the bulk solution. The influence of ionic strength on these interactions was also investigated through the addition of various monovalent and divalent salts to sample formulations. The tertiary structure of the antibody was perturbed when it adsorbed to the silicone oil–water interface in solutions at low ionic strength. However, the tertiary structure of the antibody at the interface was not perturbed when the ionic strength of the formulation was increased. Even at low ionic strength, the secondary structure of the antibody adsorbed to the silicone oil–water interface was retained, suggesting that at low ionic strength, the adsorbed antibody assumes a molten globule‐like conformation. This partially unfolded species was aggregation‐prone, especially during agitation. Silicone oil‐induced aggregation of the antibody was inhibited at higher ionic strength. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:429–440, 2013</p> </abstract>