Moisture absorption and desorption of different rubber lyophilisation closures

Abstract

Rubber closures form a critical barrier in the protection of freeze-dried products against the uptake of moisture. In this study, the moisture absorption of different rubber lyophilisation closures at different temperatures and relative humidities (RH) was evaluated, using a Karl Fischer titration–oven combination. Also, the moisture absorption during steam sterilisation and the moisture desorption during subsequent drying of the stoppers was investigated. Five chlorobutyl and three bromobutyl rubber stoppers were used in this study. The moisture level from the stoppers stored during 85 days at 95% RH–40°C was in the range 0.85–1.49% for the bromobutyl stoppers and in the range 1.71–1.99% for the chlorobutyl stoppers, depending on the stopper formulation. The same trend in moisture absorption was seen during steam sterilisation, where the moisture uptake of the chlorobutyl rubber closures was higher (0.82–0.9%) compared with the bromobutyl closures (0.41–0.57%). Moisture desorption after steam sterilisation, during drying at 100°C, depended on the treatment of the stopper, e.g., siliconation. Finally the moisture absorption of a freeze-dried formulation was evaluated after venting the lyophilisation chamber with air, dry nitrogen, dry helium or closing the vials under vacuum with two different rubber closures. There was no moisture desorption in the rubber closures during the lyophilisation process. Moisture uptake of the freeze-dried cakes depended on the venting procedure of the lyophilisation chamber after freeze-drying.