On the Use of Temperature Measurements as a Process Analytical Technology (PAT) for the Monitoring of a Pharmaceutical Freeze-Drying Process
The measurement of product temperature is one of the methods that can be adopted, especially in the pharmaceutical industry, to monitor the freeze-drying process and to obtain the values of the process parameters required by mathematical models useful for in-line (or off-line) optimization. Either a...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/15/3/861 |
| _version_ | 1797609492047724544 |
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| author | Alberto Vallan Davide Fissore Roberto Pisano Antonello A. Barresi |
| author_facet | Alberto Vallan Davide Fissore Roberto Pisano Antonello A. Barresi |
| author_sort | Alberto Vallan |
| collection | DOAJ |
| description | The measurement of product temperature is one of the methods that can be adopted, especially in the pharmaceutical industry, to monitor the freeze-drying process and to obtain the values of the process parameters required by mathematical models useful for in-line (or off-line) optimization. Either a contact or a contactless device and a simple algorithm based on a mathematical model of the process can be employed to obtain a PAT tool. This work deeply investigated the use of direct temperature measurement for process monitoring to determine not only the product temperature, but also the end of primary drying and the process parameters (heat and mass transfer coefficients), as well as evaluating the degree of uncertainty of the obtained results. Experiments were carried out with thin thermocouples in a lab-scale freeze-dryer using two different model products, sucrose and PVP solutions; they are representative of two types of commonly freeze-dried products, namely those whose structures are strongly nonuniform in the axial direction, showing a variable pore size with the cake depth and a crust (leading to a strongly nonlinear cake resistance), as well as those whose structures are uniform, with an open structure and, consequently, a cake resistance varying linearly with thickness. The results confirm that the model parameters in both cases can be estimated with an uncertainty that is in agreement with that obtained with other more invasive and expensive sensors. Finally, the strengths and weaknesses of the proposed approach coupled with the use of thermocouples was discussed, comparing with a case using a contactless device (infrared camera). |
| first_indexed | 2024-03-11T06:02:06Z |
| format | Article |
| id | doaj.art-55158aca807b4e54ad76b4371b1cb9ea |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T06:02:06Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-55158aca807b4e54ad76b4371b1cb9ea2023-11-17T13:15:25ZengMDPI AGPharmaceutics1999-49232023-03-0115386110.3390/pharmaceutics15030861On the Use of Temperature Measurements as a Process Analytical Technology (PAT) for the Monitoring of a Pharmaceutical Freeze-Drying ProcessAlberto Vallan0Davide Fissore1Roberto Pisano2Antonello A. Barresi3Department of Electronics and Telecommunications, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Torino, ItalyDepartment of Applied Science and Technology, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Torino, ItalyDepartment of Applied Science and Technology, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Torino, ItalyDepartment of Applied Science and Technology, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Torino, ItalyThe measurement of product temperature is one of the methods that can be adopted, especially in the pharmaceutical industry, to monitor the freeze-drying process and to obtain the values of the process parameters required by mathematical models useful for in-line (or off-line) optimization. Either a contact or a contactless device and a simple algorithm based on a mathematical model of the process can be employed to obtain a PAT tool. This work deeply investigated the use of direct temperature measurement for process monitoring to determine not only the product temperature, but also the end of primary drying and the process parameters (heat and mass transfer coefficients), as well as evaluating the degree of uncertainty of the obtained results. Experiments were carried out with thin thermocouples in a lab-scale freeze-dryer using two different model products, sucrose and PVP solutions; they are representative of two types of commonly freeze-dried products, namely those whose structures are strongly nonuniform in the axial direction, showing a variable pore size with the cake depth and a crust (leading to a strongly nonlinear cake resistance), as well as those whose structures are uniform, with an open structure and, consequently, a cake resistance varying linearly with thickness. The results confirm that the model parameters in both cases can be estimated with an uncertainty that is in agreement with that obtained with other more invasive and expensive sensors. Finally, the strengths and weaknesses of the proposed approach coupled with the use of thermocouples was discussed, comparing with a case using a contactless device (infrared camera).https://www.mdpi.com/1999-4923/15/3/861freeze-dryingprocess monitoringtemperature measurementtemperature sensorsthermocouplepharmaceuticals |
| spellingShingle | Alberto Vallan Davide Fissore Roberto Pisano Antonello A. Barresi On the Use of Temperature Measurements as a Process Analytical Technology (PAT) for the Monitoring of a Pharmaceutical Freeze-Drying Process Pharmaceutics freeze-drying process monitoring temperature measurement temperature sensors thermocouple pharmaceuticals |
| title | On the Use of Temperature Measurements as a Process Analytical Technology (PAT) for the Monitoring of a Pharmaceutical Freeze-Drying Process |
| title_full | On the Use of Temperature Measurements as a Process Analytical Technology (PAT) for the Monitoring of a Pharmaceutical Freeze-Drying Process |
| title_fullStr | On the Use of Temperature Measurements as a Process Analytical Technology (PAT) for the Monitoring of a Pharmaceutical Freeze-Drying Process |
| title_full_unstemmed | On the Use of Temperature Measurements as a Process Analytical Technology (PAT) for the Monitoring of a Pharmaceutical Freeze-Drying Process |
| title_short | On the Use of Temperature Measurements as a Process Analytical Technology (PAT) for the Monitoring of a Pharmaceutical Freeze-Drying Process |
| title_sort | on the use of temperature measurements as a process analytical technology pat for the monitoring of a pharmaceutical freeze drying process |
| topic | freeze-drying process monitoring temperature measurement temperature sensors thermocouple pharmaceuticals |
| url | https://www.mdpi.com/1999-4923/15/3/861 |
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