Effects of vial packing density on drying rate during freeze-drying of carbohydrates or a model protein measured using a vial-weighing technique.
OBJECTIVE
To determine the effects of vial packing density in a laboratory freeze dryer on drying rate profiles of crystalline and amorphous formulations.


METHODS
The Christ freeze-drying balance measured cumulative water loss, m(t), and instantaneous drying rate, m(t), of water, mannitol, sucrose and sucrose/BSA formulations in commercial vials.


RESULTS
Crystalline 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.


CONCLUSIONS
Plots of m(t) versus radical t and m(t) 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.
Gieseler
Henning
H
Division of Pharmaceutics, Friedrich-Alexander-University, Cauerstr. 4, 91058, Erlangen, Germany.
Lee
Geoffrey
G
D002241:Carbohydrates / Q000737:chemistry*; D005612:Freeze Drying; D008353:Mannitol / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013395:Sucrose / Q000737:chemistry; D013678:Technology, Pharmaceutical; D014199:Trehalose / Q000737:chemistry
D002241:Carbohydrates; D012710:Serum Albumin, Bovine; D008353:Mannitol; D013395:Sucrose; D014199:Trehalose