Resistance to vapor flow

D. E. Overcashier, T. W. Patapoff, and C. C. Hsu, Lyophilization of protein formulations in vials Investigation of the relationship between resistance to vapor flow during primary drying and small scale product collapse, J. Pharm. Sci., 88(7), 688 (1999). 

Once the product is adequately frozen, the next step is the removal of ice, i.e., primary drying. During primary drying, the rate of ice sublimation is dependent on the amount of heat supplied to the product. The temperature of the product equilibrates as a function of two opposite effects the transfer of heat from the shelf or from the gaseous atmosphere to the product, and the cooling due to ice sublimation. As the ice-vapor interface (moving front) moves toward the bottom of the containers, the rate of ice sublimation tends to diminish because the nascent porous matrix in the upper part of the pellet offers some resistance to vapor flow. 

The vapor risers or channels offer resistance to vapor flow. If vapor pressiu-e drop across the risers becomes equal to the liquid head above the distributor, the distributor will flood. It is therefore important to allow sufficient open area for vapor flow. This open area must be distributed evenly and in a manner that prevents formation of poorly irrigated regions directly beneath the vapor passages. 

This case is essentially quite different from the foregoing, since it is obvious that one is dealing with a kinetic process. Nevertheless, there have been several misconceptions in the literature, which arise because the full implications of the kinetic aspects have not been recognised. These implications result from the fact that a condensation stage has been introduced close by the evaporation Stage, with almost negligible resistance to vapor flow between them. The only resistance to be considered is that offered by residual inert gas to the diffusion of the zinc atoms. 

A 1% (w/v) trehalose formulation frozen by liquid nitrogen exhibited a fine filamentous directional network, whereas freezing by placement on a —50°C shelf yielded a leafy mixed-orientation appearance. The authors state that the rapidly frozen trehalose had less resistance to vapor flow during drying and reconstituted faster than the shelf-frozen samples. 

If the stopper resistance is not negligible, then the global resistance to vapor flow in... 

Figure 5.7 compares the internal structure of freeze-dried products obtained by spontaneous nucleation and by forced nucleation. As expected, the latter sample has larger pores than the sample obtained by spontaneous nudeation. As a result, samples obtained by forced nucleation are characterized by a low product resistance to vapor flow and, therefore, by faster drying rates (see Eq. 5.10). 

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