Measurement of lyophilisation primary drying rates by freeze-drying microscopy

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Measurement of lyophilisation primary drying rates by freeze-drying microscopy
S. Zhai, R. Taylor, R. Sanches and N. K. H. Slater
June 2003
Chemical Engineering Science
Abstract
The mass transfer processes that influence the rate of primary drying during lyophilisation are characterised by freeze-drying microscopy. A simple diffusion model is shown to describe the observed progress of drying fronts through isothermal, one-dimensional systems of slab and cylindrical geometry. Measured drying rates are modelled by an effective diffusion coefficient, Deff, which describes the diffusion of water vapour from the inner frozen core through the outer dried cake of the lyophilising mass. In this way, the relationship between the instantaneous thickness of the dried cake and the drying time is determined for different drying temperatures. Values of Deff determined by analysis of freeze-drying microscopy data for two simple model systems are shown to be in satisfactory agreement with those predicted from theory. Furthermore, the lyophilisation behaviour of a citrate and a tris?HCl buffer are well described by the model and values of Deff are constant at temperatures below the collapse temperatures of the dried cakes. However, values of Deff increase approximately four- and six-fold, respectively as the collapse temperatures are approached. Microscopic examination of the citrate buffer dried cake shows its structure to be homogeneous at temperatures well below the collapse temperature, as required by the model, but indicates significant cracking of the cake as the collapse temperature for this buffer (247 K) is approached. As a result, channeling of the water vapour through the dried cake causes enhanced drying rates. Finally, we show that the total time required to sublime water from aqueous slurries of glass beads in a conventional laboratory lyophiliser are in reasonable agreement with those times estimated using the values of Deff determined by freeze-drying miscroscopy.