Determination of Mass- and Heat Transfer Coefficients for Computer Modelling of Pharmaceutical Freeze-Drying
(2021) KLGM15 20211Food Technology and Nutrition (M.Sc.)
- Abstract
- This thesis work deals with the determination of mass- and heat transfer coefficients for pharmaceutical vial freeze-drying and the one-dimensional steady state computer modelling of primary drying. The overall heat transfer coefficient K_V for the vial/freeze-dryer system was successfully determined using a gravimetric method. The overall resistance to mass transfer R_p was successfully determined for a 3% sucrose solution using a heat conduction model.
The pressure rise test with the manometric temperature algorithm was also investigated as an alternative method to monitor product temperature and determine transfer parameters without success.
A novel approach using an aluminum vial holder was evaluated as a method to increase... (More) - This thesis work deals with the determination of mass- and heat transfer coefficients for pharmaceutical vial freeze-drying and the one-dimensional steady state computer modelling of primary drying. The overall heat transfer coefficient K_V for the vial/freeze-dryer system was successfully determined using a gravimetric method. The overall resistance to mass transfer R_p was successfully determined for a 3% sucrose solution using a heat conduction model.
The pressure rise test with the manometric temperature algorithm was also investigated as an alternative method to monitor product temperature and determine transfer parameters without success.
A novel approach using an aluminum vial holder was evaluated as a method to increase temperature homogeneity during primary drying. When using the vial holder, vials situated at the center and edge of the freeze-dryer shelf did not differ in freeze-drying behaviour. It could also be shown that the vial holder increased heat transfer above 10 Pa, and decreased heat transfer below 2 Pa. However, additional investigation is required to fully understand the vial holder's effect on heat- and mass transfer parameters.
MATLAB was used to simulate primary drying of 3% sucrose solution at 10 Pa and -20 degree C based on determined K_V and R_p values. A one-dimensional steady state model based on governing mass- and heat transfer equations was used. When simulating primary drying of a full freeze-dryer shelf, the drying time was overestimated by 14%. Simulation of three vials placed in the vial holder instead underestimated the drying time with 9%. Predicted product temperatures were accurate for the first hours of primary drying, after which the accuracy significantly decreased. This is partly believed to be due to the phenomenon of microcollapse in the dry cake. (Less) - Popular Abstract
- In today's society, biopharmaceuticals are an essential part of many peoples lives. Vaccines, hormones, antibody therapies and insulin are examples of biopharmaceuticals that save lives and improve life quality every day. Today, biopharmaceuticals constitute about a third of all new pharmaceuticals. Nevertheless, the formulation and production of biopharmaceuticals comes with many challenges, where the stability of the active substance is the main issue. Often, biopharmaceuticals require gentle production methods, certain types of formulations, and demanding storage conditions to remain stable.
One such production method often used in the production of biopharmaceuticals is freeze-drying. Freeze-drying is a drying-technique where the... (More) - In today's society, biopharmaceuticals are an essential part of many peoples lives. Vaccines, hormones, antibody therapies and insulin are examples of biopharmaceuticals that save lives and improve life quality every day. Today, biopharmaceuticals constitute about a third of all new pharmaceuticals. Nevertheless, the formulation and production of biopharmaceuticals comes with many challenges, where the stability of the active substance is the main issue. Often, biopharmaceuticals require gentle production methods, certain types of formulations, and demanding storage conditions to remain stable.
One such production method often used in the production of biopharmaceuticals is freeze-drying. Freeze-drying is a drying-technique where the product is dried by sublimation of ice from the frozen product. Freeze-drying is an essential part of many biopharmaceutical production processes. However, it is slow, energy demanding and expensive.
The aim of this thesis work is therefore to develop a computer based model for the drying process, to be used as support in process design and optimization of freeze-drying processes. If the drying process could be simulated with acceptable accuracy, some of the time consuming and expensive experimental work required to developing new freeze-drying processes could be avoided.
A prerequisite for modelling is that model parameters can be accurately determined. For this reason, a substantial part of this thesis work deals with the determination of mass- and heat transfer coefficients for the freeze-drying process.
In summary, this thesis work contributes to increased understanding of the freeze-drying process, how it can be modelled, and how model parameters for mass- and heat transfer can be determined. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9050265
- author
- Gustafsson, Linnea LU
- supervisor
- organization
- course
- KLGM15 20211
- year
- 2021
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- Freeze-drying, Mass- and Heat Transfer, Pharmaceutical production, Simulation, MATLAB, Pharmaceutical technology
- language
- English
- id
- 9050265
- date added to LUP
- 2021-06-11 12:18:32
- date last changed
- 2021-06-11 12:18:32
@misc{9050265,
abstract = {{This thesis work deals with the determination of mass- and heat transfer coefficients for pharmaceutical vial freeze-drying and the one-dimensional steady state computer modelling of primary drying. The overall heat transfer coefficient K_V for the vial/freeze-dryer system was successfully determined using a gravimetric method. The overall resistance to mass transfer R_p was successfully determined for a 3% sucrose solution using a heat conduction model.
The pressure rise test with the manometric temperature algorithm was also investigated as an alternative method to monitor product temperature and determine transfer parameters without success.
A novel approach using an aluminum vial holder was evaluated as a method to increase temperature homogeneity during primary drying. When using the vial holder, vials situated at the center and edge of the freeze-dryer shelf did not differ in freeze-drying behaviour. It could also be shown that the vial holder increased heat transfer above 10 Pa, and decreased heat transfer below 2 Pa. However, additional investigation is required to fully understand the vial holder's effect on heat- and mass transfer parameters.
MATLAB was used to simulate primary drying of 3% sucrose solution at 10 Pa and -20 degree C based on determined K_V and R_p values. A one-dimensional steady state model based on governing mass- and heat transfer equations was used. When simulating primary drying of a full freeze-dryer shelf, the drying time was overestimated by 14%. Simulation of three vials placed in the vial holder instead underestimated the drying time with 9%. Predicted product temperatures were accurate for the first hours of primary drying, after which the accuracy significantly decreased. This is partly believed to be due to the phenomenon of microcollapse in the dry cake.}},
author = {{Gustafsson, Linnea}},
language = {{eng}},
note = {{Student Paper}},
title = {{Determination of Mass- and Heat Transfer Coefficients for Computer Modelling of Pharmaceutical Freeze-Drying}},
year = {{2021}},
}