Modeling of Heat and Mass Transfer Processes for the Gap‐Lyophilization System Using the Mannitol–Trehalose–NaCl Formulation

ABSTRACTGap freezing (GF) is a new concept that was developed to reduce the primary drying time using an alternative freezing process. The purpose of this investigation was to determine the gap‐tray heat transfer coefficient, Kgtr, and to investigate the effect of gap lyophilization on cycle reduction of a mannitol–trehalose–NaCl (MTN) formulation. The values of Kgtr were measured using the product temperature profiles in three different configurations: (1) shelf freezing followed by shelf drying (denoted as SF–SD), (2) GF followed by SD (denoted as GF–SD), and (3) GF followed by gap drying (denoted as GF–GD). For the lyophilization cycle using shelf drying (SF–SD), 80% of the heat transferred during primary drying was from the bottom shelf to the vial, versus 20% via radiation from the top shelf. For the lyophilization cycle using gap drying (GF–GD), only 37% of the heat transferred during primary drying was from the bottom shelf to the vial versus 63% via radiation from the top shelf. Furthermore, GF in conjunction with annealing significantly reduces the dry layer resistance of the MTN formulation, which is the opposite of what was observed with a conventional freezing cycle. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2784–2796, 2014