Influence of packaging material on the liquid stability of interferon-alpha2b.

PURPOSE: In this article we studied the effect of the packaging material on the liquid stability of interferon alpha 2b (rhIFN-alpha2b). METHODS: The compatibility of this cytokine with type I borosilicate glass ampoules was evaluated by ELISA and RP-HPLC, at 4 degrees C and after heat sealing. Additionally, the influence of protein concentration (3 and 10 MIU/ml), buffer species (sodium phosphate, sodium citrate and sodium citrate-phosphate) and additives (polysorbate 80 and EDTA Na(2) x 2H(2)O) were studied in samples with and without contact with chlorobutyl stoppers by RP-HPLC. 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 alcohol-based vehicle. The effect of the heat sealing of ampoules on the stability of rhIFN-alpha2b 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(3) day-(1). This effect significantly decreased in about 1.2- and 1.1-fold when sodium citrate or sodium citrate-phosphate buffers, respectively, were evaluated. Results from the evaluation of EDTA Na(2) x 2H(2)O 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(3) day-(1). CONCLUSIONS: The adsorption of the cytokine to type I borosilicate glass ampoules was eliminated with a polysorbate 80/benzyl alcohol-based 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-alpha2b. However, protein concentration, buffer species and pharmaceutical excipients can modulate this effect.

Influence of packaging material on the liquid stability of interferon-á2b

Purpose: In this article we studied the effect of the packaging material on the liquid stability of interferon alpha 2b (rhIFN-a2b). 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 citrate-phosphate) and additives (polysorbate 80 and EDTA Na2 x 2H2O) were studied in samples with and without contact with chlorobutyl stoppers by RP-HPLC. 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 alcohol-based vehicle. The effect of the heat sealing of ampoules on the stability of rhIFN-a2b 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 103 day-1. This effect significantly decreased in about 1.2- and 1.1-fold when sodium citrate or sodium citrate-phosphate buffers, respectively, were evaluated. Results from the evaluation of EDTA Na2 x 2H2O or polysorbate 80 showed a similar behavior..........(AU)

Objeto: En este artículo se estudió el efecto del material de envasado de líquidos en la estabilidad del interferón alfa 2b (rhIFN-A2B). Métodos: La compatibilidad de este tipo de citoquinas con ampollas de vidrio borosilicato que se evaluó por ELISA y RP-HPLC, a 4 º C y después en caliente. Además, la influencia de la concentración de proteínas (3 y 10 mUI / ml), tampón de especies (fosfato sódico, citrato de sodio y citrato de sodio-fosfato) y aditivos (polisorbato 80 y EDTA Na2 x 2H2O) se estudiaron en las muestras con y sin contacto con clorobutilo tapones por RP-HPLC. Resultados: La compatibilidad de esta citocina en tampón fosfato de sodio, tipo I, con ampollas de vidrio borosilicato mostraron una absorción significativa en la concentración más baja. Esta influencia fue eliminado con un polisorbato 80/benzyl vehículo a base de alcohol. El efecto del calor y el sellado de ampollas en la estabilidad de rhIFN-A2B mostró dos picos de degradación cuando el volumen de 1 ml se dispensaron. Sin embargo, con un menor (0,5 ml) de volumen, la degradación no se detectó. Por otra parte, en contacto con las muestras de clorobutilo tapones aparente aumento de la degradación constante de velocidad en el rango de 6,74 ± 0,38 a 46,34 ± 3,11 x 103 días-1. Este efecto disminuyó significativamente, en alrededor de 1,2 y 1,1 veces al citrato de sodio o citrato de sodio, fosfato de búferes, respectivamente, fueron evaluadas. Los resultados de la evaluación de EDTA Na2 x 2H2O o polisorbato 80 mostraron un comportamiento similar. Estos aditivos de la aparente reducción de la degradación constante de velocidad en el rango de 2,01 ± 0,14 a 25,51 ± 3,57 x 103 días-1......