Heat Transfer in Freeze-Drying Apparatus

Freeze-drying is a process used to remove water (or another solvent) from a frozen product, thus increasing its shelf-life. It is extensively used in pharmaceuticals manufacturing, to recover the active pharmaceutical ingredient (and the excipients) from an aqueous solution, as well as in some food processes, because of the low operating temperatures that allow preserving product quality. Moreover, the freeze-dried product has a high surface area and can be easily re-hydrated. In this chapter we focus on pharmaceuticals manufacturing, where the solution containing the product is generally processed in vials, placed over the shelves in a drying chamber. However, it is worth stating that, in industrial practice, other loading configurations can be used to carry out the process, thus this study will be extended also to the case where vials are loaded on trays, or the solution is directly poured in trays. The process consists of three consecutive steps, namely: 1. Freezing: product temperature is lowered below the freezing point and, thus, most of the solvent freezes, forming ice crystals. Part of the solvent can remain bounded to the product, and must be desorbed. Also the product often forms an amorphous glass which can retain a high amount of water. 2. Primary drying: in this step the pressure in the drying chamber is lowered, thus causing ice sublimation. This phase is usually carried out at low temperature (ranging, in most cases, from -40°C to -10°C) and, as sublimation requires energy, heat is transferred to the product through the shelf, by acting on the temperature of the fluid flowing in the coil inserted in the shelf. 3. Secondary drying: when the sublimation of the ice has been completed, shelf temperature is raised (e.g. to 20-40°C) and chamber pressure is further decreased to allow the desorption of the water bounded to the product, thus getting the target moisture in the product. The freeze-dryer comprises the drying chamber and a condenser where the water vapour is sublimated on some cold surfaces in order to decrease the volumetric flow-rate arriving to the vacuum pump. The pressure in the chamber can be modified either by acting on a valve placed on pump discharge, or using the so called “controlled leakage”, i.e. manipulating the flow rate of nitrogen (or another gas) introduced in the chamber. The drying chamber can be isolated from the condenser by means of a valve that is usually placed in the duct connecting the chamber to the condenser (Mellor, 1978; Jennings, 1999; Oetjen & Haseley, 2004; Franks, 2007).