Rubber closures for freeze-dried products

Once a biological product has been developed to perform its required medical or pharmaceutical function, it is essential that a container-closure system by chosen which will preserve the efficacy of the product up to the point of administration. The general requirements applicable to proper closure function will be reviewed and the suitability of natural and synthetic elastomers to perform these functions will be discussed. The specialized application of elastomeric materials as closures for freeze-dried products presents additional requirements which are superimposed upon those previously discussed. The first of these unique considerations relates to the proper physical design which will permit the outgassing of water vapor during the sublimation step in the lyophilizing chamber. During this outgassing the design must also permit the closure to remain affixed in the neck while only partially inserted. Since these preparations are lyophilized because they are unstable in aqueous solutions, the elastomer used must constitute an effective barrier to the transmission of moisture vapor through the closure. The MVT and gas transmission properties of elastomers will be discussed. Special consideration will be given to the extremely low temperatures used in the sublimation, stoppering, and storage before use of lyophilized products. The phenomenon of glass transition points with different elastomers will be explained as its relation to satisfactory performance of the closure function at low temperatures.