Collapsed Cakes

Nov 16, 2011
By PharmTech Editors
Untitled Document

Q: We have changed the brand of our stoppers for a product that we freeze-dry in vials. Since the change, we have observed a significant increase in rejects for collapsed cakes. Why are the cakes collapsing? What can we do to prevent this problem?

A: When selecting stoppers, we take great care to specify various details, such as the formulation of the rubber, the quality of its surface, and the surface treatment, out of concern for the stability of our product. One important specification, however, is sometimes overlooked. This specification is the surface area of the openings or windows in the stopper that result when the stopper is placed on the vial at the prestoppering stage. The window is the route by which water vapor exits the vial during sublimation and desorption; it restricts the passage of vapor.

When you changed the brand of stoppers, you may have reduced the surface area of the window inadvertently. Smaller windows provide greater restriction and could increase the pressure inside the vial, thus causing a consequent increase in sublimation-front temperature. If this temperature exceeds the collapse temperature, you will find an increased number of collapsed cakes. Examine the window geometries of your old and new brands of stoppers and evaluate whether they have equivalent surface areas.

—Robert Bullich, process development manager at TELSTAR

 

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