Freeze drying process

Freeze Drying. Commercial freeze drying of instant coffee has been a common practice in the United States since the mid-1960s. The freeze-drying process provides the opportunity to minimize flavor degradation due to heat (34). 

Fig. 7 Collapse is characteristic of amorphous materials, and can occur either during the freeze-dry process or during storage. 

A. P. MacKenzie, The physicochemical basis for the freeze-drying process Dev. Biol. Stand., 36, 51-67 (1977). 

The objective of the primary drying stage of the freeze-drying process is to remove the ice as quickly as possible without undue risk of product loss... 

MJ Pikal. Use of laboratory data in freeze drying process design Heat and mass transfer coefficients and the computer simulation of freeze drying. J Parenter Sci Tech-nol 39 115-138, 1985. 

The freeze-drying process is initiated by the freezing of the biopharmaceutical product in its final product containers. As the temperature is decreased, ice crystals begin to form and grow. This results in an effective concentration of all the solutes present in the remaining liquid phase, including the protein and all added excipients. For example, the concentration of salts may increase to... 

As the temperature is lowered further, the viscosity of the unfrozen solution increases dramatically until molecular mobility effectively ceases. This unfrozen solution will contain the protein, as well as some excipients, and (at most) 50 per cent water. As molecular mobility has effectively stopped, chemical reactivity also all but ceases. The consistency of this solution is that of glass, and the temperature at which this is attained is called the glass transition temperature Tg-. For most protein solutions, Tg- values reside between -40 °C and -60 °C. The primary aim of the initial stages of the freeze-drying process is to decrease the product temperature below that of its Tg- value and as quickly as possible in order to minimize the potential negative effects described above. 

The next phase of the freeze-drying process entails the application of a vacuum to the system. When the vacuum is established, the temperature is increased, usually to temperatures slightly in excess of 0 °C. This promotes sublimation of the crystalline water, leaving behind a powdered cake of dried material. Once satisfactory drying has been achieved, the product container is sealed. 

Fig. 1.62. Course of a freeze drying process in a plant, as shown in Fig. 1.65. Pressure control during MD is not activated. 1.0 kg product in four aluminum trays with machined bottoms, Tsh after evacuation controlled at +29 °C, d = 0,6 cm.

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.

Hatley, R. H. M. The effective use of differential scanning calorimetry in the optimisation of freeze-drying processes and formulations. Developments in Biological Standardization Vol. 74, p. 105-122. Acting Editors Joan C. May, F. Brown S. Karger AG, CH-4009 Basel (Switzerland), 1992... 

Willemer, H. Water vapour pressure, its influence on the freeze-drying process and its control. 40th Annnual Congress of the International Association for Pharmaceutical Technology, Abstracts 1-67, Medpharm GmbH, Scientific Publishers, Stuttgart, Marz 1994... 

Fig. 2.17. Coils in a condenser covered by ice, observed through a window during two freeze drying processes. Left Smooth, solid surface. Right Porous, snow-like surface, which occurs typically, if the pressure of permanent gases during MD is high (photographs Dr. Otto Suwalck, D-48727 Billerbeck).

Chase [2.32] presents an alternative method to monitor and control the freeze drying process by measuring the flow of nitrogen to keep the operation control pressure, pc, constant. The Mass Flow Controller (FMC) consists of a proportional valve, an integral flow meter and a capacitance manometer (CA). The CA measures the total pressure in the plant, the valve opens, if the pressure gets below the preset value and vice versa. The flow of... 

With this start-up the most critical machine data are to check No remaining ice, cooling and heating working, and leak rate acceptable. The procedure takes some time, but minimizes problems occuring during the freeze drying process. 

An important step in the freeze drying process with vials is the stoppering or closing of the vials either at the end pressure of SD, or at a chosen partial pressure of a specific gas. This avoids handling of open vials, which can lead to contamination and adsorption of water vapor from the atmosphere. 

Therefore, it is decisive for the freeze drying process which follows that the filled vials during this time pass through a known and reproducible course of temperature. The prod-... 

Oetjen, G. W. Freeze-Drying Processes and Equipment, XVIII. Congresso Nationale del Freddo, Padua, June 1969... 

In addition, the transplants may have a larger layer thickness to be dried than in other freeze drying processes. It is recommended in one charge to freeze dry transplants of similar layer thickness (the size can vary). 

The merit of Malinin s work is the comparative study of water content of bones by reproducible methods. The measurement of water vapor pressure during the drying cannot be used dirctly to determine the RM, as Malinin correctly states. Measurement of the description rates (DR) provide a means to follow quantitatively the course of desorption drying. The method is described in Section 1.2.2, but cannot be applied in an installation used by Malinin because the condenser cannot be separated from the chamber by a valve. By using the data given in the paper of Malinin it is possible to estimate the freeze drying process of bone transplants as follows ... 

Wiliemer, H. Freeze-drying process data determination for human blood derivates with factor VIII as example. PDA Fourth International Congress, p. 142-151, Vienna, 1996. Copyright 1996, PDA Inc. Bethesda, Maryland, USA... 

The general rule for all freeze drying processes applies also to food The method of freezing, the freezing rate and the final temperature of freezing largely determine the quality of... 

In Section 2.2.8, possible failures during the freeze drying process are classified in four categories, and the preventions and necessary actions briefly discussed. In this chapter, some unexpected or undesirable events are studied which, by experience may happen. The problems listed here are selected from the course of the freeze drying process. A breakdown of single components, for example pumps, compressors or valves are not included in this chapter. The list will be incomplete, but an attempt has been made to mention some of the more frequent events. The problems with leaks and their hunting is discussed in Section 2.2.8. 

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