title: Modeling of heat and mass transfer processes for the gap-lyophilization system using the mannitol-trehalose-NaCl formulation.
abstract: Gap 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.
authors.affiliation: Pharmaceutical Development, Baxter Healthcare Corporation, Round Lake, Illinois 60073. Electronic address: wei_kuu@baxter.com.
authors.forename: Wei Y
authors.initials: WY
authors.lastname: Kuu
authors.affiliation: Pharmaceutical Development, Baxter Healthcare Corporation, Round Lake, Illinois 60073.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Doty
authors.affiliation: Pharmaceutical Development, Baxter Healthcare Corporation, Round Lake, Illinois 60073.
authors.forename: Eugen
authors.initials: E
authors.lastname: Nisipeanu
authors.affiliation: Pharmaceutical Development, Baxter Healthcare Corporation, Round Lake, Illinois 60073.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Rebbeck
authors.affiliation: Bioscience Technical Services, Baxter Healthcare Corporation, Thousand Oaks, California 91362.
authors.forename: Yong K
authors.initials: YK
authors.lastname: Cho
authors.affiliation: Bioscience Technical Services, Baxter Healthcare Corporation, Thousand Oaks, California 91362.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Smit
mesh_terms: D000465:Algorithms; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003890:Desiccation / Q000379:methods; D005612:Freeze Drying; D005615:Freezing; D006358:Hot Temperature; D008353:Mannitol / Q000737:chemistry*; D008956:Models, Chemical; D012965:Sodium Chloride / Q000737:chemistry*; D014199:Trehalose / Q000737:chemistry*
chemical_list: D008353:Mannitol; D012965:Sodium Chloride; D014199:Trehalose
keywords: algorithm; crystallization; diffusion; freeze-drying; heat transfer; lyophilization; mathematical model; porosity; transport