title: Modeling the Secondary Drying Stage of Freeze Drying: Development and Validation of an Excel-Based Model.
abstract: Although several mathematical models of primary drying have been developed over the years, with significant impact on the efficiency of process design, models of secondary drying have been confined to highly complex models. The simple-to-use Excel-based model developed here is, in essence, a series of steady state calculations of heat and mass transfer in the 2 halves of the dry layer where drying time is divided into a large number of time steps, where in each time step steady state conditions prevail. Water desorption isotherm and mass transfer coefficient data are required. We use the Excel "Solver" to estimate the parameters that define the mass transfer coefficient by minimizing the deviations in water content between calculation and a calibration drying experiment. This tool allows the user to input the parameters specific to the product, process, container, and equipment. Temporal variations in average moisture contents and product temperatures are outputs and are compared with experiment. We observe good agreement between experiments and calculations, generally well within experimental error, for sucrose at various concentrations, temperatures, and ice nucleation temperatures. We conclude that this model can serve as an important process development tool for process design and manufacturing problem-solving.
authors.affiliation: Global Manufacturing Science and Technology, Pfizer Inc., McPherson, Kansas 67460; Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut 06269.
authors.forename: Ekneet K
authors.initials: EK
authors.lastname: Sahni
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut 06269. Electronic address: michael.pikal@uconn.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pikal
mesh_terms: D003198:Computer Simulation / Q000592:standards; D003460:Crystallization; D003890:Desiccation / Q000379:methods*; D005612:Freeze Drying / Q000379:methods / Q000592:standards; D015203:Reproducibility of Results; D013395:Sucrose / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D013696:Temperature
chemical_list: D013395:Sucrose
keywords: Excel-based model; freeze drying; heat and mass transfer; lyophilization process; mass transfer coefficient; secondary drying