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Abstract: With computational modeling of lyophilization in vials, the pressure coupling between the sublimation front and the drying chamber has traditionally been calculated using a simplified mass transfer resistance model in the form of a model, which takes into account the headspace and the stopper in a simplified way. In developing a 3D CFD-based digital twin of lyophilization in vials, a need arises for a mass flow rate-dependent vial headspace/stopper model, as it enables a more accurate calculation of the pressure conditions above the shelf as well as pressure conditions directly at the sublimation front, the latter directly affecting the sublimation mass transfer rate as well as the temperature inside the product, which is crucial for determining the risk of product collapse. The local pressure variations at a shelf level affect the heat transfer conditions due to heat conduction in the low pressure environment of the drying chamber. In the present work the development of a coupled multilevel vial lyophilization model for the freeze-drying of vials is reported, with the time-dependent 1D heat and mass transfer model at the vial level coupled with the time-dependent 3D low-pressure CFD model of the flow of the water vapor–air mixture in the drying chamber heated by the shelves. A direct pressure coupling between the sublimation front and the drying chamber space in form of vial type specific headspace/stopper resistance model is implemented. The developed multilevel lyophilization model is used to study the pressure build-up above the shelf and the headspace of the vial and its influence on the product temperature at the bottom of the vial using simulations carried out for different chamber pressures (6 Pa and 22 Pa), shelf temperatures (−20 oC and +10 oC) and vial types (10R and 15R). By implementing previously developed vial headspace/stopper pressure resistance models, the computational results show that the pressure build-up above the shelf and vial headspace significantly affect the product temperature at the bottom of the vial, especially at low chamber pressures ( Pa) and small gap sizes between the rubber stopper and the shelf above it. The increased pressure outside the vial leads also to higher heat transfer by conduction, which is particularly pronounced at the central shelf positions and within smaller shelf gaps. These results underline the importance of using a coupled multilevel model when analyzing the relationship between the local pressure variations above the shelf and their direct influence on product drying conditions, further improving the predictive capabilities of CFD based multilevel lyophilization models, especially with respect to detecting the product collapse temperature.
Keywords: freeze-drying, conjugate heat and mass transfer, computational fluid dynamics, multi-scale modeling
Published in DKUM: 17.06.2025; Views: 0; Downloads: 4
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Abstract: The saponification of an aromatic ester with an aqueous sodium hydroxide was studied within a heterogeneous reaction medium in order to determine the overall kinetics of the selected system. The extended thermo-kinetic model was developed compared to the previously used simple one. The reaction rate within a heterogeneous liquid-liquid system incorporates a chemical kinetics term as well as mass transfer between both phases. Chemical rate constant was obtained from experiments within a homogeneous medium, whilst the mass-transfer coefficient was determined separately. The measured thermal profiles were then the bases for determining the overall reaction-rate. This study presents the development of an extended kinetic model for considering mass transfer regarding the saponification of ethyl benzoate with sodium hydroxide within a heterogeneous reaction medium. The time-dependences are presented for the mass transfer coefficient and the interfacial areas at different heterogeneous stages and temperatures. The results indicated an important role of reliable kinetic model, as significant difference in $k_La$ product was obtained with extended and simple approach.
Keywords: chemical kinetics, mass transfer, saponification, heterogeneous system
Published in DKUM: 25.08.2017; Views: 1794; Downloads: 228
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Abstract: A genetic algorithm with resizable population has been applied to the estimation of parameters for Sovovaćs mass transfer model. The comparison of results between a genetic algorithm and a global optimizer from the literatureshows that a genetic algorithm performs as good as or better than a global optimizer on a given set of problems. Other benefits of the genetic algorithm, for mass transfer modeling, are simplicity, robustness and efficiency.
Keywords: Sovova's mass transfer model, genetic algorithm, parameter estimation
Published in DKUM: 31.05.2012; Views: 1902; Downloads: 90
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Abstract: This article describes experimental determination of the relative impact of significant process parameters that influence volumetric oxygen mass transfer coefficient (kLa) using Taguchi design methodology. For this purpose an automated RC1 reaction calorimeter (Mettler-Toledo), which was originally developed for chemical processes, was modified for the bioprocesses. Simple fermentation using Baker's yeast was studied to illustrate the design procedure. Orthogonal array L25 was selected for the proposed design and ANOVA method was used for recognizing the relative influence of the process parameters. Within the observed range of temperature (?), fermentation media volume (VFM), and yeast mass concentration (?Y), these process parameters were found to be unimportant compared to the volumetric air flow rate (qV,a) and rotational frequency of the stirrer (fm). The qV,a had a substantial effect on the kLa value (89.2 %) and the fm had just a small one (3.6 %), meanwhile the remain fraction to 100 % represents error. The results refer strictly to the selected case study. Anyhow, the proposed procedure shows that application of the Taguchi approach for analyzing the oxygen mass transfer based on the experimental data obtained from a highly-automated laboratory reactor appears to have potential usage in general biopharmaceutical process design.
Keywords: bioprocess parameters, mass transfer, volumetric oxygen mass transfer coefficient, process parameters, Taguchi method, analysis of variance
Published in DKUM: 31.05.2012; Views: 2551; Downloads: 58
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