Before the various process steps for freeze-drying are described in detail, this section is intended to provide an overview of the process flow sequence.
Prior to loading a new product, the freeze-drying system must be dry and any residual water from the previous run must be removed from the ice condenser chamber. The drain valve for emptying the ice condenser and the ventilation valve for venting the product chamber when the freeze-drying process is complete are then closed. The product should not be more than 1–2 cm thick, as otherwise the drying time will be excessively long.
As shown in Figure 4.1, the freeze-drying process can be controlled by selecting and modifying just two master parameters for the device:
- the vacuum setting
- the shelf temperature
where both target values can be time-dependent curves.
As indicated in previous session, the product is frozen in small amounts inside the ice condenser chamber (single chamber method) or separately in a deep-freeze unit in the lab area (dual chamber method). As a rule, freezing takes place at atmospheric pressure, similar to a conventional freezer.
Drying the product in round-bottom flasks or closeable wide-mouth filters is popular and has the advantage of being able to place or remove these containers separately in the freeze-dryer without disturbing the drying process for the other bottles. As will be explained later on, the thickness that is so important for the drying time in this area of application can be significantly reduced by freezing under rotation, as opposed to conventional static freezing. Taking advantage of centrifugal force, a uniform ice layer is produced on the cylindrical wall of the glass container.
With separate freezing, it is helpful to pre-chill the shelves, especially for small volumes of product, in order to avoid partial thawing during transport to the freeze-dryer and evacuation.
In parallel with the freezing process, the device should run through what is called a warm-up / cool-down phase: the vacuum pump can then warm up by running against the closed pressure control valve, which improves its performance and its resistance to water vapor. At the same time, the ice condenser is pre-chilled in order to be able to separate out the water vapor produced in the next step, primary drying. The preparation phase should last between 15 and 30 minutes.
To start the sublimation process, the pressure control valve to the vacuum pump is opened, so that a vacuum is applied to the freeze-dryer. Primary drying is started.
During primary drying, the frozen water or solvent is removed as vapor from the product to be dried by means of sublimation. The vapor is transported out of the product due to the differential pressure and temperature in the chamber to the surface of the ice condenser and is desublimated at the cold ice condenser.
Figure 4.2 shows a process graph for a ceramic suspension. Due to its freezing point near 0 °C and uncomplicated product properties, it can be freeze-dried using a fairly rough vacuum of 1 mbar, with a high energy input (shelf temperature +40 °C). The product temperature probes in the suspension (yellow, green, blue curves) reach values close to the shelf temperature when approaching the end of drying. Before this, a “mixed temperature” is measured, from the ice temperature and the temperature of the already dried cake. The ice condenser temperature (black curve) collapses from -83 °C to about -70 °C when primary drying starts, as large amounts of water vapor need to be desublimated. After about 20 hours, this quantity has dropped off enough that the ice condenser reaches about -85 °C again.
Optional final drying involves lowering the vacuum to the most severe, lowest possible value in conjunction with increased shelf temperature. These two measures improve desorption. For this desorption step, other thermodynamic principles apply than those in the actual sublimation.
An increase in temperature and decrease in pressure have a positive effect on the residual moisture level that can be achieved.
When the process has ended, the drying chamber is vented via the ventilation valve. It is also possible to “vent” the system with nitrogen or another inert gas via the ventilation valve. The product can then be removed.
Subsequent thawing of the ice condenser takes place at room temperature, or most quickly by means of the hot gas defroster integrated in the freeze-dryer. The melt water is drained off via the drain valve and captured in a container. Before starting a new process, residual water should be removed from the system. The drain and ventilation valves are closed again, and the system is loaded again.