Effects of Vial Packing Density on Drying Rate during Freeze-drying of Carbohydrates or a Model Protein Measured using a Vial-weighing Technique

PurposeTo determine the effects of vial packing density in a laboratory freeze dryer on drying rate profiles of crystalline and amorphous formulations.MethodsThe Christ freeze-drying balance measured cumulative water loss, m(t), and instantaneous drying rate, $$\mathop m\limits^ \cdot \left( t \right)$$, of water, mannitol, sucrose and sucrose/BSA formulations in commercial vials.ResultsCrystalline mannitol shows drying rate behaviour indicative of a largely homogeneous dried-product layer. The drying rate behaviour of amorphous sucrose indicates structural heterogeneity, postulated to come from shrinkage or microcollapse. Trehalose dries more slowly than sucrose. Addition of BSA to either disaccharide decreases primary drying time. Higher vial packing density greatly reduces drying rate because of effects of radiation heat transfer from chamber walls to test vial.ConclusionsPlots of m(t) versus √t and $$\mathop m\limits^ \cdot \left( t \right)$$versus layer thickness (either ice or dried-product) allow interpretation of changes in internal cake morphology during drying. Vial packing density greatly influences these profiles.