Effect of Polysorbate 80 Concentration on Thermal and Photostability of a Monoclonal Antibody

Abstract

Abstract. Polysorbate 80 is widely used in protein formulations to protect protein against agitationinduced aggregation. In this study, we address concerns about residual peroxide present in Polysorbate 80 on protein stability. Residual peroxide may oxidize active pharmaceutical ingredients leading to reduced stability and may ultimately lead to lower potency and efficacy. The effect of Polysorbate 80 concentration on thermal and photostability of monoclonal antibody of the IgG1 subclass (MAb1) was evaluated at Polysorbate 80 concentrations ranging from 0.00% to 1.00% (w/v). MAb1 samples at 5 mg/ mL with various Polysorbate 80 concentrations were subjected to accelerated thermal stress by incubation at 25°C, 40°C, and 50°C for a period of 4 weeks and light stress per ICH guideline Q1B, option 1. Our results show that Polysorbate 80 concentration of 1.00% (w/v) adversely affected thermal and photostability of MAb1. This study demonstrates the importance of carefully choosing Polysorbate 80 concentration in protein formulations to prevent destabilizing effect of Polysorbate 80 on thermal and photostability.

Evaluation of aggregate and silicone-oil counts in pre-filled siliconized syringes: An orthogonal study characterising the entire subvisible size range

“…Protein destabilising effects in increasing polysorbate concentrations have been observed in other studies (Agarkhed et al, 2013;Amand Bhaskar, 2014). In this study, no significant differences in aggregate formation were observed between the two PS-20 concentrations (Figure 2), although a higher concentration of silicone-oil droplets is observed in the 0.05% w/v concentration (Figures 3-4).…”

“…There are numerous studies assessing the mechanisms of mAb aggregation (Li et al, 2011;Morris et al, 2009) and the effects of silicone-oil (Basu et al, 2013;Gerhardt et al, 2014;Jones et al, 2005;Weinbuch et al, 2013b) or polysorbate surfactants (Agarkhed et al, 2013;Khan et al, 2015) in influencing the aggregation process; such studies include novel methods to reduce in situ mAb aggregation in PFS (Depaz et al, 2014). However, the focus has been the larger sub-visible size range of particulates i.e.…”

Effect of Polysorbate 20 and Polysorbate 80 on the Higher-Order Structure of a Monoclonal Antibody and Its Fab and Fc Fragments Probed Using 2D Nuclear Magnetic Resonance Spectroscopy

“…Other plausible explanation underlying peak volume loss can be the presence of transient attractive intermolecular protein interactions in NMR samples. Although no significant changes were observed in the global conformational stability of mAb and its Fab and Fc fragments upon the addition of polysorbates, conformational destabilization of proteins by polysorbates have been observed in other proteins 68–71 . For example, PS20 has been shown to reduce the thermodynamic stability of human interferon-γ and darbepoetin 24,69 .…”

Formulation Optimization and Performance Evaluation of Papain and Clove Oil based Chemo-mechanical Caries Removing Gel

“…Increase in concentration of both factors resulted in decrease of papain activity which might be due to distruption of protective layer of pectin due to tween 80 as surface active agent. 21 Optimized formulation selected has 2.5 g papain, 0.5g clove oil, 2.5 g pectin, 2.5 g propylene glycol, 0.125 g tween 80, 0.0094 g potassium di-hydrogen phosphate, 0.032 g disodium hydrogen phosphate, 0.025g methyl paraben, 0.0025g propyl paraben which showed highest % activity of papain indicating its stability and viscosity of 7800cps due to which it can be easily retained on carious tooth cavity. Efficacy of developed formulation against bacterial infection and caries removal were important parameters of evaluation.…”