title: Impact of Different Elastomer Formulations on Moisture Permeation through Stoppers Used for Lyophilized Products Stored under Humid Conditions.
abstract: The purpose of this study was to evaluate the effect of moisture permeability of different elastomer formulation stoppers, which had different moisture absorption abilities, on the increase of moisture content inside lyophilized vials during long-term storage under humid conditions. Two different elastomer formulation stoppers (high-moisture and low-moisture uptake stoppers) were compared. The increased amount of moisture content inside lyophilized vials fitted with high-moisture stoppers was higher than those fitted with low-moisture stoppers during the early stage of storage. However, this trend was reversed during the later stage of storage. Our data show that the moisture increase inside the lyophilized vials at the early stage was caused by moisture transfer from the stoppers, whereas the later moisture increase was caused by external moisture permeation through the stoppers. Results indicate that the difference in the moisture uptake profile inside the lyophilized vials at each period of storage was caused by the moisture absorption ability and moisture permeation ability of the two elastomer formulation stoppers. In terms of long-term storage stability under humid conditions, our data indicate that external moisture permeating through the stopper into the lyophilized vial during the late stage was the more important factor. In addition, the increase in moisture content at the early stage was controlled by stopper drying time. Furthermore, stopper drying time did not have an effect on moisture permeation at the late stage. Moisture permeation during the storage period appears to be dependent on the different elastomer formulations of the stoppers. The moisture permeation of different elastomer stoppers was an important factor in terms of the increased moisture content inside the lyophilized vials during the late stage of long-term storage under humid conditions. For lyophilized products stored at room temperature, the moisture permeation ability of the stopper is one of the most important factors for long-term storage stability.
authors.affiliation: Formulation Technology Research Department, Chugai Pharmaceutical Co., Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Jun
authors.initials: J
authors.lastname: Kikuchi
authors.forename: Terutoshi
authors.initials: T
authors.lastname: Maeda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kuboniwa
mesh_terms: D001688:Biological Products; D003890:Desiccation; D020724:Elastomers; D005612:Freeze Drying; D006358:Hot Temperature; D010539:Permeability; D044366:Transition Temperature; D014867:Water
chemical_list: D001688:Biological Products; D020724:Elastomers; D014867:Water