The nonsteady state modeling of freeze drying

: "Pharm Dev Technol. 2005 ;10:17-32 [Pubmed] [Scholar] [Select] [Drop] [Hide] [Show]
The nonsteady state modeling of freeze drying: in-process product temperature and moisture content mapping and pharmaceutical product quality applications.
M J Pikal, S Cardon, Chandan Bhugra, F Jameel, S Rambhatla, W J Mascarenhas, H U Akay
INTRODUCTION: Theoretical models of the freeze-drying process are potentially useful to guide the design of a freeze-drying process as well as to obtain information not readily accessible by direct experimentation, such as moisture distribution and glass transition temperature, Tg, within a vial during processing. Previous models were either restricted to the steady state and/or to one-dimensional problems. While such models are useful, the restrictions seriously limit applications of the theory. An earlier work from these laboratories presented a nonsteady state, two-dimensional model (which becomes a three-dimensional model with an axis of symmetry) of sublimation and desorption that is quite versatile and allows the user to investigate a wide variety of heat and mass transfer problems in both primary and secondary drying. The earlier treatment focused on the mathematical details of the finite element formulation of the problem and on validation of the calculations. The objective of the current study is to provide the physical rational for the choice of boundary conditions, to validate the model by comparison of calculated results with experimental data, and to discuss several representative pharmaceutical applications. To validate the model and evaluate its utility in studying distribution of moisture and glass transition temperature in a representative product, calculations for a sucrose-based formulation were performed, and selected results were compared with experimental data. THEORETICAL MODEL: The mod"