Qualities of the Dry Substances and their Changes

Changes of the physical structure of the product, e. g. from an amorphous to a partially or totally crystalline one. 

Often changes occur which have to be accounted for as a combination of several of the four categories. In this chapter some typical examples are given, though some special changes are also mentioned in Chapters 3 and 4. 

The stability of moisture-sensitive drugs has been studied by Vromans and Schalks [1.143] using amorphous vecuronium bromide. Its decomposition in a formulation depends more on the water activity aw (see Chapter 4, point 2) than on the water content. Glass-forming excipients may not only be cryoprotective but also stabilizing. 

Examples of the fourth type of changes were described by To and Flink [ 1.931 and Van Scoik and Carstensen [ 1,94 According to To and Flink the change from an amorphous to a crystalline phase is induced either by to high storage temperatures T(T Tc) or by water 

The purity of gases used should also be specified, as certain impurities can have a decisive effect on storage behavior, e. g. gas desorption from stoppers. Greiff and Rightsel [1.96] have shown that influenza viruses without CPAs keep their infectivity best when stored with 1.6 % RM in helium. In argon, the infectivity decreases approx. 10 times and in 02 20 times faster if the average of the storage temperatures is used. 

During the storage of a freeze-dried product, its qualities can change under the influence of at least three conditions residual moisture content, storage temperature and gas mix in the packing, assuming that the freeze-drying itself has been carried out under optimum conditions and the product had the intended qualities at the end 

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