Variables influencing the freeze-drying process

The two variables most strongly affecting the freeze-drying process are pressure and temperature. Temperature (or, rather, a temperature difference) is the driving force for heat transport. Energy moves from locations of higher temperature to locations of lower temperature. Similarly, pressure differences are the driving force for mass transport. The 

The freezing step is conducted at atmospheric pressure. It is crucial to ensure that the product will be thoroughly frozen by the end. This entails maintaining the temperature below the eutectic or collapse point of the product. 

In order to freeze the product, the shelf temperature is reduced to a level well below the collapse temperature. Depending on the dimensions of the container and on the fill volume of the product, the product temperature is maintained at shelf level for a specified period of time to ensure the formation of a completely frozen matrix. 

In general, the term shelf temperature as applied to freeze-drying refers to the shelf fluid rather than to the shelf surface temperature. The shelf temperature may represent the fluid temperature in a reservoir, the inlet or outlet temperature of the fluid to the shelves or the fluid temperature in the inlet or outlet of the shelf manifold. To avoid ambiguity, it is preferable to use shelf temperature to refer to a measured shelf fluid temperature. 

In the absence of a product temperature monitor, the formation of a completely frozen matrix relies on the length of time the product is on a shelf at a given fluid temperature. For vials loaded into the dryer on trays, additional time must be allocated to compensate for the variation in the heat transfer properties of the trays. 

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