Permeability of Freeze-Drying Cake Pressure Rise Tests

Permeability of Freeze-Drying Cake Pressure Rise Tests 

The pressure rise analysis method (PRA method), recently proposed by Chouvenc et al. (2004a), derived from the MTM method originally developed by Milton et al. (1997) and next modified by Obert (2001), appears to be a very promising noninvasive control method. It is a rapid, simple to implement and averaging tool that requires a freeze-dryer equipped with an external condenser and a very fast closing separating valve. The values of the main freeze-drying parameters, such as the temperature of the sublimation front, T , the resistance to water vapor mass transfer of the dried layer, J p, and the overall heat transfer coefficient, could be 

If the freeze-drying process is controlled by water vapor mass transfer through the freeze-dried layer - for example in the case of dried cake of very low permeability or for very favorable heat transfer conditions - the drying rate for one vial is proportional to the mean driving force P - Pc) - that is, to the water vapor pressure difference between the sublimation front interface and the drying chamber - and controlled by the freeze-dried cake mass transfer resistance, denoted J p, which is inversely proportional to the dried layer permeability defined by Darcy s law. Inthiscaseitholds  

Several techniques to determine experimentally the values of the freeze-dried cake mass transfer resistance, Rp, have been reported in the literature (Pikal, 1985 Patapoff et al., 1999). They were all based on the gravimetric method used either for a single vial or for a limited number of vials. In contrast to such methods, the estimation of Rp values from the P RA model allows the determination of the mean freeze-dried product mass transfer resistance for the whole vial batch, averaging the heterogeneities of the cake structures between individual vials generated by the random nucleation phenomena. As shown in Fig. 3.6, a typical set of Rp values identified by the PRA model by 

Chouvenc et al. (2004a) was compared with the predictions of the two previously quoted MTM models. The position of the sublimation interface and the thickness of the dry layer, denoted were estimated as functions of time by simple mass balances. Chouvenc et al. (2004a) observed that the Rp values derived from the three models were similar for 6 mm and slightly lower than the few literature values. Moreover, experimental data correlation lines pass close to the axis origin, so that no significant crust effect was present in the experimentally investigated crystalline system (mannitol), in contrast to what is observed with concentrated vitreous systems that can present relatively large crust effects. 

---