Humidity induced collapse in freeze dried cakes: A direct visualization study using DVS.

Maintaining low moisture content is seen as crucial to sustaining long term stability in freeze dried (FD) cakes as higher moisture could lead to cake collapse, degradation and a loss of biological potency. Using a combination of gravimetric data and video images captured from a Dynamic Vapour Sorption instrument the onset humidity Collapse Point (RH), the humidity onset Crystallisation (RH) and onset Glass Transition (RH) points for a series of freeze dried cakes at 10, 25 and 40 °C have been determined. The moisture sorption behavior with respect to cake collapse and other morphological phase transitions are reported for a two freeze drying excipients and one product formulation; sucrose, trehalose (both 5% w/w) and an influenza antigen (A/Wisconsin/15/2009 H3N2 NYMCX-183, formulated with 1.1% w/w sucrose). Stability maps for all three formulations tested were reported as a function of %RH and temperature using the methods described in this work, thus the direct visualization of collapse behavior for any FD cake can now be standardized and routinely determined, facilitating the formulation of FD products with improved stability and storage performance.