Formulation Stabilization and Disaggregation of Bevacizumab, Ranibizumab and Aflibercept in Dilute Solutions

Pharmaceutical Research
Steven A GiannosJiyang Cai

Abstract

Studies were conducted to investigate dilute solutions of the monoclonal antibody (mAb) bevacizumab, mAb fragment ranibizumab and fusion protein aflibercept, develop common procedures for formulation of low concentration mAbs and identify a stabilizing formulation for anti-VEGF mAbs for use in in vitro permeation studies. Excipient substitutions were screened. The most stabilizing formulation was chosen. Standard dilutions of bevacizumab, ranibizumab and aflibercept were prepared in PBS, manufacturer's formulation, and the new formulation. Analysis was by SE-HPLC and ELISA. Stability, disaggregation and pre-exposure tests were studied. When Avastin, Lucentis and Eylea are diluted in PBS or manufacturer's formulation, there is a 40-50% loss of monomer concentration and drug activity. A formulation containing 0.3% NaCl, 7.5% trehalose, 10 mM arginine and 0.04% Tween 80 at a pH of 6.78 stabilized the mAbs and minimized the drug loss. The formulation also disaggregates mAb aggregation while preserving the activity. Degassing the formulation increases recovery. We developed a novel formulation that significantly stabilizes mAbs under unfavorable conditions such as low concentration or body temperature. The formulation allows for tis...Continue Reading

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Citations

Aug 3, 2019·Pharmaceutics·Laura García-QuintanillaAnxo Fernández-Ferreiro
Dec 15, 2020·International Journal of Pharmaceutics·Stefania C CarraraHarald Kolmar

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Methods Mentioned

BETA
protein folding
ELISA
Enzyme-Linked Immunosorbent Assay
size-exclusion chromatography
Size Exclusion HPLC
enzyme-linked immunoassay

Software Mentioned

Excel
SigmaPlot

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