Influence of packaging material on the liquid stability of interferon-α2b

Purpose: In this article we studied the effect of the packaging material on the liquid stability of interferon alpha 2b (rhIFN-α2b). Methods: The compatibility of this cytokine with type I borosilicate glass ampoules was evaluated by ELISA and RP-HPLC, at 4oC and after heat sealing. Additionally, the influence of protein concentration (3 and 10 MIU/ml), buffer species (sodium phosphate, sodium citrate and sodium citratephosphate) and additives (polysorbate 80 and EDTA Na2 x 2H2O) were studied in samples with and without contact with chlorobutyl stoppers by RPHPLC. Results: The compatibility of this cytokine in sodium phosphate buffer, with type I borosilicate glass ampoules showed a significant adsorption at the lowest concentration. This influence was eliminated with a polysorbate 80/benzyl alcoholbased vehicle. The effect of the heat sealing of ampoules on the stability of rhIFN-α2b showed two degradation peaks when a volume of 1 ml was dispensed. However, with a lower (0.5 ml) volume, the degradation was not detected. On the other hand, samples in contact with chlorobutyl stoppers increased the apparent degradation rate constant in the range of 6.74 ± 0.38 to 46.34 ± 3.11 x 10 day. This effect significantly decreased in about 1.2and 1.1-fold when sodium citrate or sodium citratephosphate buffers, respectively, were evaluated. Results from the evaluation of EDTA Na2 x 2H2O or polysorbate 80 showed a similar behavior. These additives reduced the apparent degradation rate constant in the range of 2.01 ± 0.14 to 25.51 ± 3.57 x 10 day. Conclusions: The adsorption of the cytokine to type I borosilicate glass ampoules was eliminated with a polysorbate 80/benzyl alcoholbased vehicle, and the deleterious effect of the heat sealing decreased with a lower (0.5 ml) volume. Experimental data indicated that the contact with chlorobutyl stoppers accelerates the degradation of rhIFN-α2b. However, protein concentration, buffer species and pharmaceutical excipients can modulate this effect.