Heat Transfer in Freeze-Drying Apparatus

Pisano, Roberto; Fissore, Davide; Barresi, Antonello

doi:10.5772/23799

Cited by 51 publications

(89 citation statements)

References 31 publications

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“…As reported by Pisano et al [27,28], the vials located after the second row from the border of the shelf can be considered as equivalent to central vials. Thus, a number of 100 central vials (named M in Figure 1B) and 62 edge vials, among which 38 were in contact (C vials in Figure 1B) and 24 were not in contact with the rail (E vials in Figure 1B), were weighed before and after the run using a PG503-S DeltaRange balance (accuracy ± 0.001g; Mettler Toledo, Zaventem, Belgium).…”

Section: Sublimation Heat Flow Evaluationmentioning

confidence: 95%

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3D mathematical modelling to understand atypical heat transfer observed in vial freeze-drying

Scutellà

Plana-Fattori

Passot

et al. 2017

Applied Thermal Engineering

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In pharmaceutical freeze-drying, the position of the product container (vial) on the shelf of the equipment constitutes a major issue for the final product quality. Vials located at the shelf edges exhibit higher product temperature than vials located at the centre, which in turn often results in collapsed product. A physics-based model was developed to represent heat transfer phenomena and to study their variation with the distance from the periphery of the shelf. Radiation, conduction between solids, and conduction through low-pressure water vapour were considered. The modelling software package COMSOL Multiphysics was employed in representing these phenomena for a set of five vials located at the border of the shelf, close to the metallic guardrail. Model predictions of heat fluxes were validated against experimental measurements conducted over a broad range of shelf temperatures and chamber pressures representative for pharmaceutical freeze-drying. Conduction through low-pressure water vapour appeared as the dominant mechanism explaining the additional heat transfer to border vials compared to central ones. The developed model constitutes a powerful tool for studying heterogeneity in freeze-drying while reducing experimental costs. Highlights:• A 3D mathematical model of heat transfer in freeze-drying is proposed.• The role of several heat transfer mechanisms is explored.• Knudsen effect is considered for conduction inside low-pressure water vapour.• Radiation heat transfer is evaluated using the surface-to-surface model.• Atypical heat transfer is explained mainly by gas conduction rather than radiation.

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Section: Sublimation Heat Flow Evaluationmentioning

confidence: 95%

“…In freeze-drying, pseudo-stationary state can be assumed because of the slow dynamics of the process [6,23,27,29]. Under this condition, the net heat flow rate ̇ at the sublimation interface is directly proportional to the mass flow rate :…”

Section: Sublimation Heat Flow Evaluationmentioning

confidence: 99%

3D mathematical modelling to understand atypical heat transfer observed in vial freeze-drying

Scutellà

Plana-Fattori

Passot

et al. 2017

Applied Thermal Engineering

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“…Once all the ice was sublimated, the shelf temperature was further increased to +20 • C for 5 hours to promote water desorption. The mass transfer coefficient was estimated by firstly determining the heat transfer coefficient between the container and the heating shelf, K v , using the gravimetric procedure described in [5]. This operation needs to be applied only once provided that the containers are not varied during the test.…”

Section: Resultsmentioning

confidence: 99%

“…Most of these tools require the knowledge of heat and mass transfer coefficients [4] of containers and dried cakes. The heat transfer coefficient depends only on the type of employed container and its location on the shelf and can be measured with relative easiness [5]. On the contrary, the mass transfer coefficient is product-specific [6], depends on the conditions used during freezing [7], its evaluation requires a labor-intensive process [8] [9] and only few experts can manage it independently.…”

Section: Introductionmentioning

confidence: 99%

Wavelet image decomposition for characterization of freeze-dried pharmaceutical product structures

Grassini

Angelini

Pisano

et al. 2015

2015 IEEE International Instrumentation and Measurement Technology Conference (I2MTC) Proceedings

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This paper investigates the use of a wavelet image decomposition applied to electron microscope images in order to estimate the mass transfer coefficient of pharmaceutical cakes obtained by freeze-drying. The structure analysis of dried cakes obtained by means of a free-drying process, is a basic step for tuning the process conditions and for monitoring the quality of the dried product. The product structure and specifically its porosity affects the drying duration as it defines the resistance to the vapor flow during the ice sublimation. This parameter is becoming quite important as it is fundamental for modeling of the freeze-drying process and thus for an optimal design of the freeze-drying cycle. The direct measurement of this parameter is quite complex thus new simple approaches are being developed for its non-invasive estimation. This paper discusses the possibility of processing SEM images of the dried cake to analyze its morphology and to estimate the mass transfer coefficient. This approach has already been followed by processing the images via a 2D-FFT, here a faster solution based on the image wavelet decomposition followed by a non-linear processing based on an artificial neural network is described and the results are compared with the one obtained by the traditional direct mass transfer coefficient measurement.

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“…Also, both techniques assume that product dynamics is the same in all the vials of the batch, thus estimating ''mean values'' of temperature, residual amount of ice, K v and R p as the batch of vial is actually not uniform (mainly) due to different heat transfer mechanisms to the product and to uncontrolled ice nucleation temperature. [42][43][44][45] Velardi et al [46,47] designed an observer to monitor in-line a freeze-drying process. An observer is a tool based on the following elements:…”

Section: Introductionmentioning

confidence: 99%

Design of a Robust Soft-Sensor to Monitor In-Line a Freeze-Drying Process

2014

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This article deals with the in-line monitoring of a vital freeze-drying process using a soft-sensor that couples the experimental measurement of product temperature with a mathematical model of the process. This tool allows estimating in-line the residual amount of ice in the product and, thus, the duration of the primary drying stage, as well as some model parameters like the heat transfer coefficient between the shelf and the product and the resistance of the dried cake to vapor flow. As the performance of this sensor, based on the Extended Kalman Filter algorithm, strongly depends on the accuracy of the initial estimations of model parameters, an innovative algorithm based on a simple model of the freezing stage (and on product temperature measurement in this stage) is first used to roughly estimate the dried cake resistance to vapor flow. Then, a curvilinear regression algorithm is used in the first part of the primary drying stage with the goal of further refining model parameters' estimations. In this way, the robustness of the sensor is significantly improved, as confirmed by various experiments carried out to validate the soft-sensor and to investigate the effect of the accuracy of the initial estimations of model parameters on the performance of the system.

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Heat Transfer in Freeze-Drying Apparatus

Cited by 51 publications

References 31 publications

3D mathematical modelling to understand atypical heat transfer observed in vial freeze-drying

3D mathematical modelling to understand atypical heat transfer observed in vial freeze-drying

Wavelet image decomposition for characterization of freeze-dried pharmaceutical product structures

Design of a Robust Soft-Sensor to Monitor In-Line a Freeze-Drying Process

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