title: Mechanistic modelling of infrared mediated energy transfer during the primary drying step of a continuous freeze-drying process.
abstract: Conventional pharmaceutical freeze-drying is an inefficient and expensive batch-wise process, associated with several disadvantages leading to an uncontrolled end product variability. The proposed continuous alternative, based on spinning the vials during freezing and on optimal energy supply during drying, strongly increases process efficiency and improves product quality (uniformity). The heat transfer during continuous drying of the spin frozen vials is provided via non-contact infrared (IR) radiation. The energy transfer to the spin frozen vials should be optimised to maximise the drying efficiency while avoiding cake collapse. Therefore, a mechanistic model was developed which allows computing the optimal, dynamic IR heater temperature in function of the primary drying progress and which, hence, also allows predicting the primary drying endpoint based on the applied dynamic IR heater temperature. The model was validated by drying spin frozen vials containing the model formulation (3.9mL in 10R vials) according to the computed IR heater temperature profile. In total, 6 validation experiments were conducted. The primary drying endpoint was experimentally determined via in-line near-infrared (NIR) spectroscopy and compared with the endpoint predicted by the model (50min). The mean ratio of the experimental drying time to the predicted value was 0.91, indicating a good agreement between the model predictions and the experimental data. The end product had an elegant product appearance (visual inspection) and an acceptable residual moisture content (Karl Fischer).
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: PieterJan.VanBockstal@UGent.be.
authors.forename: Pieter-Jan
authors.initials: PJ
authors.lastname: Van Bockstal
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience Engingeering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium. Electronic address: Severine.Mortier@UGent.be.
authors.forename: Séverine Thérèse F C
authors.initials: ST
authors.lastname: Mortier
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: Laurens.DeMeyer@UGent.be.
authors.forename: Laurens
authors.initials: L
authors.lastname: De Meyer
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: Jos.Corver@RheaVita.nl.
authors.forename: Jos
authors.initials: J
authors.lastname: Corver
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: Chris.Vervaet@UGent.be.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.affiliation: BIOMATH, Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience Engingeering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium. Electronic address: Ingmar.Nopens@UGent.be.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Nopens
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: Thomas.DeBeer@UGent.be.
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
mesh_terms: D000465:Algorithms; D002138:Calibration; D003890:Desiccation / Q000379:methods*; D004339:Drug Compounding; D004735:Energy Transfer; D005544:Forecasting; D005612:Freeze Drying / Q000379:methods*; D007259:Infrared Rays; D008956:Models, Chemical; D058996:Quality Improvement; D015203:Reproducibility of Results; D019265:Spectroscopy, Near-Infrared; D013696:Temperature
keywords: Continuous freeze-drying; Infrared radiation; Mechanistic modelling; Spin freezing