Micro Freeze-Dryer and Infrared-Based PAT: Novel Tools for Primary Drying Design Space Determination of Freeze-Drying Processes

Harguindeguy, Maitê; Fissore, Davide

doi:10.1007/s11095-021-03023-x

Cited by 4 publications

(9 citation statements)

References 49 publications

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“…For this reason, freezing is usually regarded as complete when the solution reaches the eutectic point (

) for crystalline solutes or the glass transition temperature (

) for amorphous ones. The

for 5% sucrose is 241 K, 264 K for 10% dextran, while the

for 5% mannitol is 251.7 K [ 49 , 50 ]. However, in this study, the interval between nucleation and the product reaching nearly 263 K was the only one closely examined.…”

Section: Resultsmentioning

confidence: 99%

Investigation of the Freezing Phenomenon in Vials Using an Infrared Camera

et al. 2021

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The freezing phenomenon has a dramatic impact on the quality of freeze-dried products. Several freezing models applied to solutions in vials have been proposed to predict the resulting product morphology and describe heat transfer mechanisms. However, there is a lack of detailed experimental observations of the freezing phenomenon in vials in the literature. Thus, the present work offers new experimental observations of the freezing phenomenon in vials by infrared (IR) thermography. IR imaging allowed each vial’s whole axial temperature profile to be collected during freezing, providing significant insights into the process. Spontaneous nucleation and vacuum-induced surface freezing (VISF), as a controlled nucleation technique, are investigated. Batches having vials in direct contact with the shelf (exchanging heat mainly through conduction) as well as suspended (exchanging heat mainly through natural convection and radiation) were tested. The study used three solutions: sucrose 5%, mannitol 5%, and dextran 10%. SEM images coupled with an automated image segmentation technique were also performed to examine possible correlations between the freezing observations and the resulting pore size distributions. IR thermography was found to be a promising tool for experimentally predicting the resulting product morphology in-line.

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“…For this reason, freezing is usually regarded as complete when the solution reaches the eutectic point (

) for crystalline solutes or the glass transition temperature (

) for amorphous ones. The

for 5% sucrose is 241 K, 264 K for 10% dextran, while the

for 5% mannitol is 251.7 K [ 49 , 50 ]. However, in this study, the interval between nucleation and the product reaching nearly 263 K was the only one closely examined.…”

Section: Resultsmentioning

confidence: 99%

Investigation of the Freezing Phenomenon in Vials Using an Infrared Camera

et al. 2021

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“…The calculation to simulate the primary drying was based on a steady-state heat balance for the frozen product. To this end, the overall heat exchange coefficient, K v , was determined nongravimetrically, using the IR-based end-time determination method as proposed by Harguindeguy and Fissore (2020) . In this method, because sublimation is an endothermic process, the sublimation interface temperature ( T i ) was monitored during primary drying by tracking the minimum axial temperature, T min .…”

Section: Experimental Sectionmentioning

confidence: 99%

“…Because IR is noninvasive and it does not interfere with the sample, the temperature rise when sublimation is completed served as a consistent primary drying end-time determination method. By assuming that all water sublimated in the time interval is defined by the T min tracking method, the K v could be determined nongravimetrically . The average value of K v for the six ON-shelf batches was 33.0 ± 4.4 W·m –2 ·K –1 .…”

Section: Experimental Sectionmentioning

confidence: 99%

“…The sublimation interface temperature, T i , was calculated recursively together with R p using well-known one-dimensional heat exchange models and suitable assumptions. For the sake of brevity, they are not described here, as they were described in detail by Harguindeguy and Fissore 2021 . The only addition done in the present work was a different equation for the R p calculation.…”

Section: Experimental Sectionmentioning

confidence: 99%

“…To overcome this problem, it is possible to use different technologies . Freezing was experimentally studied using simple image analysis to obtain the freezing progression in a solution. , In recent years, many papers have been produced to validate and study the application of infrared (IR) imaging as a noninvasive method to obtain in-line temperature measurements during freeze-drying. − This technology is up-and-coming not only because it does not interfere with the process itself but also because it can provide temperature distributions among vials both in the freezing and in the drying stages. The ability to obtain a full thermogram of the products temperature profile provides an almost complete knowledge of the system without introducing additional heat transfer models.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Combining Mathematical Modeling and Thermal Infrared Data in the Freezing of Pharmaceutical Liquid Formulations

Harguindeguy

Stratta

Fissore

et al. 2022

Ind. Eng. Chem. Res.

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Infrared-based (IR) thermal imaging data was combined here with mathematical modeling to describe the freezing process of a pharmaceutical formulation being lyophilized using two different loading configurations; (i) vials in direct contact with the shelf and (ii) vials suspended over it. In all the experiments, the nucleation event was trigged at a specific time instant using the vacuum induced surface freezing (VISF) method. The IR thermal data was given as input to three different mathematical models for freezing and used to estimate the resulting cake’s pore size (d p ) distribution. The resulting d p values were then compared to experimental data obtained through SEM images coupled with an image segmentation tool. The supersaturation model showed the best agreement between the estimated d p and experimental values, while minor discrepancies were shown by the other two models. Nonetheless, the outcomes of these last two models, given as inputs to a mathematical model for the primary drying phase, resulted in satisfactory predictions of the product temperature at the moving front, the product resistance to vapor flow, and the primary drying end point. It follows that the combination of the IR thermocamera and freezing modeling is a promising tool for the in-line monitoring and optimization of a freeze-drying cycle.

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