Heat; mass transfer scale-up issues during freeze-drying, III: Control; characterization of dryer differences via operational qualification tests
The objective of this research was to estimate differences in heat; mass transfer between freeze dryers due to inherent design characteristics using data obtained from sublimation tests. This study also aimed to provide guidelines for convenient scale-up of the freeze-drying process. Data obtained from sublimation tests performed on laboratory-scale, pilot,; production freeze dryers were used to evaluate various heat; mass transfer parameters: nonuniformity in shelf surface temperatures, resistance of pipe, refrigeration system,; condenser. Emissivity measurements of relevant surfaces such as the chamber wall; the freeze dryer door were taken to evaluate the impact of atypical radiation heat transfer during scale-up. “Hot”; “cold” spots were identified on the shelf surface of different freeze dryers,; the impact of variation in shelf surface temperatures on the primary drying time; the product temperature during primary drying was studied. Calculations performed using emissivity measurements on different freeze dryers suggest that a front vial in the laboratory lyophilizer received 1.8 times more heat than a front vial in a manufacturing freeze dryer operating at a shelf temperature of 25°C; a chamber pressure of 150 mTorr during primary drying. Therefore, front vials in the laboratory are much more atypical than front vials in manufacturing. Steady-state heat; mass transfer equations were used to study a combination of different scaleup issues pertinent during lyophilization cycles commonly used for the freeze-drying of pharmaceuticals.
S. Rambhatla1?S. Tchessalov1?Michael J. Pikal1Email:pikal@uconnvm.uconn.edu
[1] School of Pharmacy, University of Connecticut, 06269 Storrs, CT ;[2] Present address: Talecris Biotherapeutic, Inc., Clayton, NC ;[3] Present address: Wyeth BioPharma, Drug Products Development, Andover, MA
