Control systems, freeze-drying pressure

Fig. 1.69. Course of a freeze drying process during which Tke has not been kept constant at -26.8 °C. To avoid the declining temperature, either Tsh could have been increased after 2 h (difficult to control, the inertia of the heating system is substantial) or pc increased until Tkt is constant at -26,8 °C. 1, pch (TM) 2, pch (CA) 3, Tpt (RTD) 4, Tke (BTM) 5, end of pressure control.

The dryer should possess temperature sensors to measure the shelf and product temperatures throughout the freeze-drying process. Most freeze-dryers can be equipped with a computer system to control the pressure in the chamber and the shelf temperature as a function of time. The product temperature allows one to confirm that the shelf temperature and chamber pressure are within their preset limits. 

During freeze-drying, the condenser temperature creates a low-pressure zone in the dryer for vapour to migrate. Such a zone should therefore be maintained at a preset, low level. If such a level is exceeded, then a pressure rise in the system can cause the product to melt down. Freezer-dryers equipped with condenser overload controls automatically cool the shelves until the emergency is solved. 

The complete unsteady-state optimal control problem has been stndied by Litchfield and Liapis [12] for a system where 0 and q = 0 using turkey meat and nonfat-reconstituted milk as model foodstuffs. The results of the dynamic analysis for nonfat-reconstituted milk confirm the suggested control policies of the quasisteady-state analysis. At low chamber pressures the dynamic analysis with turkey meat showed control results similar to those obtained by the quasi-steady-state analysis. However, at higher pressures the assumed control policy based on the quasisteady-state analysis was not optimal. The optimal control dynamic study of Litchfield and Liapis [12] suggested that the policies of the quasisteady-state analysis may be useful guidelines but they should be interpreted with some caution. To obtain accurate optimal control policies on the heat input and chamber pressure of the freeze drying proeess, the complete unsteady-state optimal control problem should be solved [76,78,79,82,83]. 

Eissore, D., Pisano, R., Barresi, A. A., 2009a. On the design of an in-line control system for a vial freeze-drying process the role of chamber pressure. Chem. Prod. Proc. Model. 4 (2) 1-20. 

Pressure senor, for freeze-drying chamber 14, Vacuum breakage valve, for freeze-drying 15, Temperature sensor 16, Freeze-dryer vacuum valve 17, MWFD vacuum valve 18, Cold trap 19, Vacuum pump 20, Draining valve 21, Refrigeration compressor 22, Control system. 

For safety reasons, the pressure is set in such a way that the temperature is 5°C below the melting point of the product. On an hourly basis, the freeze-dryer automatically uses a drain valve to allow the pressure within the system to drop. A simultaneous fall in product temperature is indicative of the presence of frozen solvent that should thus be extracted during the sublimation or primary drying step. Detecting any residual solvent in this way avoids the risk of the product melting down. Before the desorption step is started, this pressure control cycle is repeated until no further drop in product temperature is observed. 

There are two different types of water sprinkler systems, wet-pipe and dry-pipe. The lines leading to the sprinkler heads are full of water in a wet-pipe system so that water will be discharged immediately from an open sprinkler head, while in a dry-pipe system, the lines are full of air under pressure instead of water. This latter type of unit should be used where the temperature is not maintained above freezing at aU times. Both types of systems include a main control valve which is designed not only to supply water to the sprinkler heads but also to provide a mechanism to cause an alarm to sound. The valves also usually provide a visual indication of whether they are open or closed. Except during maintenance, they should be in the open position. There are a number of design features for these valves which are beyond the scope of this document, except to note that some are intended to avoid false alarms due to surges or variations in the water supply pressure to the system. 

The co-solvent system that has been most extensively evaluated was the tert-butanol/water combination. The tert-butanol possesses a high vapor pressure, freezes completely in most commercial freeze-dryers, readily sublimes during primary drying, can increase sublimation rates, and has low toxicity. This co-solvent system is being used in the manufacture of a marketed injectable pharmaceutical product. When using this solvent system, both formulation and process control required optimization to maximize drying rates and to minimize residual solvent levels at the end of drying. 

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