Gravimetric Measurement of Momentary Drying Rate of Spray Freeze-Dried Powders in Vials

ABSTRACT: The profile of drying rate versus primary drying time for a spray freeze- dried trehalose aqueous solution is much different from that determined for regular freeze-drying. Drying rate declines very rapidly, attributed to rate-limiting heat transfer through the packed bed of frozen microparticles contained in a vial. The inter-particulate spaces appear to be the cause of this rate limitation. Use of either liquid nitrogen or liquid propane as a cryogenic produced strong differences in both SFD particle morphology and drying rate using trehalose, sucrose, or mannitol. The lack of any evident correlation supports the argument that the inter-particulate voids determine drying behavior. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3447–3455, 2009