.png)
The Relevance of Product Resistance in Primary Drying
ABSTRACT:
Product resistance (Rp) has been recently suggested as a critical product parameter (CPtP) in freeze drying because it instantaneously draws a picture of the (already dried) inner cake morphology at the point of measurement. From a physical point of view, Rp of the dried product layer impacts the resistance to water vapor flow and thus indirectly determines the maximally allowable shelf temperature and primary drying time. With higher product resistance the product temperature increases and mass flow decreases. Product resistance data allow the assessment of structural changes in the cake (e.g. microcollapse, shrinkage or collapse) as a function of temperature during primary drying. Moreover, product resistance data obtained during primary drying can reveal changes in the freezing situation of a batch (e.g. supercooling, nucleation) or can simply confirm consistency of the freezing behavior between batches during scale-up.
Three methods for assessing dry layer resistance can be currently found in the literature: a high-vacuum microbalance technique, a single vial method and Manometric Temperature Measurement (MTM) where the product resistance is derived from non-linear regression analysis of a MTM model equation.
Close Window