Split-Cakes, Still Delicious

“Elegant” lyophilized pharmaceutical product cakes are expected to appear as uniform foamy plugs with little shrinkage and minimal cracking. While studying internal cake structures, we have on occasion observed some cakes that were very sharply split horizontally, roughly in halves, with foamy top and lamellar bottom regions. After many years and numerous experiments, we can finally propose a mechanism for the formation of these cakes with unusual internal structures. This phenomenon involves a complex interplay of momentum, heat, mass transfer, and phase equilibria. LAY ABSTRACT: Freeze drying (lyophilization) is a common unit operation in the manufacturing of pharmaceutical drugs. The typical final lyophilized product is expected to look like a uniform porous plug, or cake, that has foamy (sponge-like) morphology. However, we have occasionally observed cakes that were split horizontally, with the top and bottom layers exhibiting very distinctive and totally different structures. This intriguing phenomenon has not been discussed in the literature. In this report, we present experimental results that lead us to a mechanism by which split-cakes form.