Freeze-drying deleterious processes

Slow freezing often results in a concentrated cellular mass in the central portion of the specimen as well as a large interstitial network of concentrated fluids, both of which are deleterious in the drying process. To overcome this phenomenon, methods to cool the specimen evenly are required. 

A typical pharmaceutical formulation will serve as model, frozen aqueous solutions that are contained in loosely stoppered glass vials. They stand directly on the freeze-drier shelves. Such a model appears deceptively simple but is in fact subject to considerable complexities that bedevil the modelling of optimum processing conditions and the estimation of a realistic drying cycle time. As emphasised in earlier chapters, for the case where the product does not display eutectic behaviour, it is imperative to freeze the solution to below Tg, in order to ensure maximal freeze-concentration and minimise deleterious chemical reactions that have been shown to occur at high rates in part frozen, supersaturated mixtures.By the same token, the temperature during the removal of ice by sublimation must on no account be allowed to rise above T at... 

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