title: Investigation of freeze-drying sublimation rates using a freeze-drying microbalance technique.
abstract: This study was to investigate the effects of different freeze-drying factors on the rate of sublimation. The experiments were carried out in a custom-built freeze-drying microbalance to accurately monitor the sample temperature and control the chamber pressure. Twenty-four experiments were conducted based on a full factorial design by changing four factors: freezing rate (fast freezing or slow freezing), chamber temperature (35, 0, or -35 degrees C), chamber pressure (30 or 1000 mTorr), and the presence or absence of an annealing process. Lactate dehydrogenase (LDH), a tetrameric protein, was selected as a model protein for this study. The statistical analysis of the experimental results revealed that chamber temperature, analogous to the shelf temperature, in this experiment system, had the greatest impact on the sublimation rate. High chamber temperature resulted in high sublimation rate, regardless of the chamber pressure and thermal history of the sample. Chamber pressure was an important factor affecting the sublimation rate. In addition, both chamber temperature and chamber pressure had significant impact on sample temperature during freeze-drying. Annealing the samples was the most critical step to preserve good freeze-dried cake structure.
authors.affiliation: Bayer Healthcare, LLC, 800 Dwight Way, P.O. Box 1986, Berkeley, CA 94701-1986, USA. jun.xiang.b@bayer.com
authors.forename: Jun
authors.initials: J
authors.lastname: Xiang
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Hey
authors.forename: Volker
authors.initials: V
authors.lastname: Liedtke
authors.forename: D Q
authors.initials: DQ
authors.lastname: Wang
mesh_terms: D000399:Air Pressure; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005612:Freeze Drying / Q000295:instrumentation / Q000379:methods*; D007770:L-Lactate Dehydrogenase / Q000737:chemistry; D013223:Statistics as Topic; D013696:Temperature; D044366:Transition Temperature
chemical_list: D007770:L-Lactate Dehydrogenase