title: Evaluation of spin freezing versus conventional freezing as part of a continuous pharmaceutical freeze-drying concept for unit doses.
abstract: Spin-freezing as alternative freezing approach was evaluated as part of an innovative continuous pharmaceutical freeze-drying concept for unit doses. The aim of this paper was to compare the sublimation rate of spin-frozen vials versus traditionally frozen vials in a batch freeze-dryer, and its impact on total drying time. Five different formulations, each having a different dry cake resistance, were tested. After freezing, the traditionally frozen vials were placed on the shelves while the spin-frozen vials were placed in aluminum vial holders providing radial energy supply during drying. Different primary drying conditions and chamber pressures were evaluated. After 2h of primary drying, the amount of sublimed ice was determined in each vial. Each formulation was monitored in-line using NIR spectroscopy during drying to determine the sublimation endpoint and the influence of drying conditions upon total drying time. For all tested formulations and applied freeze-drying conditions, there was a significant higher sublimation rate in the spin-frozen vials. This can be explained by the larger product surface and the lower importance of product resistance because of the much thinner product layers in the spin frozen vials. The in-line NIR measurements allowed evaluating the influence of applied drying conditions on the drying trajectories.
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium. Electronic address: laurens.demeyer@ugent.be.
authors.forename: L
authors.initials: L
authors.lastname: De Meyer
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
authors.forename: P-J
authors.initials: PJ
authors.lastname: Van Bockstal
authors.affiliation: RheaVita, High Tech Campus 9, NL 5656 AE Eindhoven, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Corver
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Vervaet
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: De Beer
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying; D005615:Freezing; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D005079:Excipients
keywords: Continuous freeze drying; Freeze-drying; NIR spectroscopy; Spin freezing