Pharmaceuticals freeze-drying

Oetjen, G. W. Industriel freeze-drying for pharmaceutical applications, Table 3, p. 288. Pharmaceutical freeze-drying, edited by Louis Rey, Joan C. May, copyright 1999 by Marcel Dekker, Inc. New York, N. Y. 

Monger, P. Freeze Dryer Validation, p. 157. Good Pharmaceutical Freeze-Drying Practice, Editor Cameron. P., Interpharm Press, Inc., Buffalo Grove, If, USA 1997... 

The heat transfer in the temperature range used in pharmaceutical freeze-drying, -60°C to +60°C, is dominated by contact between surfaces and by convection of the gas between the surfaces. The possible effect of radiation will be studied later. 

K. Murgatroyd, The freeze-drying process. In Good Pharmaceutical Freeze-Drying Practice (P. Cameron, ed.), Interpharm Press, Buffalo Grove, IL, 1997, pp. 1-58. 

Studies on Development of Manufacturing Processes for Pharmaceutical Freeze-Dried Products... 

For a detailed discussion of lyophilization, the reader is referred to Jennings (1999). In addition, a thorough review of the manufacturing and regulatory aspects of lyophilization is provided in Good Pharmaceutical Freeze-Drying Practice (Cameron 1997). 

In the following discussion, emphasis is placed on the classes of solutes that are of importance in pharmaceutical freeze-drying they include salts and some water-soluble organic compounds, specifically those that can act as hydrogen-bond donors and/or acceptors. As shown in Figure 10, solutes exert a major influence on ice nucleation and, hence, also on ice crystallisation rates and crystal habits. An additional factor to be taken into account is the fate of the solutes during freeze-concentration. 

An example of a previously unknown hydrate was recently reported for mannitol, a commonly used excipient in pharmaceutical freeze-drying. It was formed inadvertently during the particular drying protocol used. It was identified as a hydrate by X-ray diffraction, differential scanning calorimetry (DSC) and thermogravimetry, and it will be further discussed in a later chapter. 

In pharmaceutical freeze-drying operations, excipients fulfil several functions. These include ... 

In pharmaceutical freeze-drying, on the other hand, importance is placed not on mass, but on activity/unit mass, and the parameters that govern survival of some biological activity in small volumes are totally different and more subtle than they are for a simple dewatering process. 

When all the free water present in the cake in the form of ice crystals has been removed by sublimation, the freeze-drying process has to be terminated by a final desorption step to eliminate the bound water of the product. This desorption step is required to reach a moisture content inferior to around 2%, which is very common for a pharmaceutical freeze-dried product. This step is achieved under high vacuum so that the product can lose a substantial part of its bound water at above zero temperature. 

Fissore, D., Pisano, R., Barresi, A. A., 2011a. Advanced approach to build the design space for the primary drying of a pharmaceutical freeze-drying process./. Pharm. Sci. 100(11) 4922-4933. 

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