Physical stability of bevacizumab solutions for intravitreal injections: Influence of conditioning material and storage conditions

The treatment of numerous retinal pathologies requires the use of intravitreal medications administered and compounded in medical 3-piece syringes. Particle formation influenced by storage conditions is a source of concern as it can have clinical impacts such as endophtalmitis or reduced visual acuity. The aim of this work was therefore to investigate and compare the physical stability of bevacizumab stored in syringes made of polypropylene lubricated with silicone oil (PP-SOL) or Cyclic Olefin Copolymer with crosslinked silicone at the surface of the barrel (COC-CLS). 0.2 mL of bevacizumab solutions were conditioned in both syringes types and the physical stability and particles or aggregate generation was followed after 3 days, 1 month and 3 months of storage, under three different storage conditions: refrigerated temperature (5 ± 3 °C), with or without mechanical stress after the storage period to simulate user manipulations before patient administration, and heat stress temperature (35 ± 2 °C). Particle counting, dynamic light scattering, size exclusion chromatography, size diffusion by taylor dispersion analysis, Fourier transform infrared spectroscopy, scanning electron microscopy and microanalysis X and calculated aggregation index via UV visible absorption were performed on the samples. Overall, the COC-CLS syringes generated less particles than the PP-SOL ones, in particular when submitted to a mechanical stress. The physical stability of the bevacizumab solutions was superior in COC-CLS syringes than in PP-SOL syringes.