Freeze-drying vial closure

Freeze dried vials are usually partially stoppered just before entering the dryer. Closures are seated into the vials mechanically at the end of the drying cycle. A typical freeze drying flow diagram is shown in Fig. 6. 

The current challenges to moisture measurement include devising methods to deal with smaller and smaller sample sizes in single-dose final containers, working with samples that are very sensitive to ambient humidity even in the dry box, and understanding the interaction between water in the freeze-dried cake, the vial head space, and the container closure, and the changes that occur over time. 

At the completion of the freeze-dry cycle, the partially inserted rubber closures are fully seated in the vials. The finished product contains a white or off-white sterile dry powder. 

Figure 1 The variety found in freeze-dried final containers includes flame-sealed glass ampoules and many sizes of glass vials with container closures. 

What is true for the container in the container-closure system is equally true for the closure alone and, essentially, for the elastomeric stoppers, generally butyl rubber, which cap the vial. Fran DeGrazio from West Pharmaceutical Services has done a lot of research in this field and studied many alternatives to their formulation trying to keep down the extractables (essentially volatile) and leachables and prevent adsorption of oils, waxes, polymers, and others on the freeze-dried plug. 

Silylation procedure. Add 1.0 ml of the internal standard soln. and 80 pi of N-trimethylsilyldi-ethylamine (Pierce) to each vial containing the freeze-dried sample. Heat the vial in a 75°C oil bath for 40 min. Silylated neomycins thus prepared are extremely sensitive to moisture and better stability may be obtained when the sample is prepared in a l.S-ml serum vial with a I3-mm natural red rubber closure Calculations... 

Stoppers may also slide into the vials and cause their virtual closure. This can happen during freezing of the product, especially if the shelf temperatures are very low. The dimensions of the stoppers need to be tested not only for the pressure to close them after drying, but also for shrinking at low temperatures. 

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