Communications Project

Document Type:Dissertation
Name:James Patrick Dolan
Title:Use of Volumetric Heating to Improve Heat Transfer During Vial Freeze-Drying
Degree:Doctor of Philosophy
Department:Mechanical Engineering
Committee Chair: Elaine P. Scott
Committee Members:Werner E. Kohler
Curtis H. Stern
James R. Thomas
William C. Thomas
Keywords:freeze-drying, volumetric heating, microwave heating, heat transfer
Date of defense:June 30, 1998
Availability:Release the entire work for Virginia Tech access only.
After one year release worldwide only with written permission of the student and the advisory committee chair.


Freeze-drying (lyophilization) is a drying process which is used to remove water from heat sensitive products, usually for the purpose of preservation. By removing water, the product becomes more stable at room temperature. This is a common process in the pharmaceutical industry because freeze-drying offers the advantage of drying at low temperatures and producing very low residual moisture contents. Often the materials dried in this manner are heat sensitive and require the highest possible quality. However, freeze-drying is a very slow process, often requiring 24 to 48 hours. During the process, vacuum pumps and refrigeration systems run continuously, making freeze-drying a very expensive process.

The goal of this project was to show that volumetric heating can be used in pharmaceutical freeze-drying and that this mode of heating offers some advantages. There were two approaches taken to the work, one experimental and one analytical. The experimental approach was broken into two phases, one focused on comparing microwave and conventional freeze-drying and the other focused on demonstrating the advantages of volumetric heating. In the analytical approach, a mathematical model was used to confirm the trends observed in phase II of the experimental work.

Experiments were conducted in a conventional laboratory freeze-dryer and the drying rate results were compared to the results obtained with an experimental microwave freeze-drying apparatus. Experiments were also conducted with the vaccine strain A. pleuropneumoniae. A viability study was conducted, comparing the viability loss caused by each process. The viability study showed a slightly higher viability loss for the microwave process.

A comparison of drying curves showed that the microwave process resulted in a slight improvement in primary drying time: 2.5 hours for the microwave process compared to 3 hours for the conventional process. There was a significant difference in overall drying times: 4 hours for the microwave process compared to 11 hours for the conventional process. This result was caused by a lower residual moisture content at the start of secondary drying and a higher secondary drying temperature for the microwave process.

Experiments were also conducted to show that using lower chamber pressure results in higher drying rates. This is not the case in a conventional freeze-dryer since heating is dependent on the chamber pressure in the low pressure environment of freeze-drying. Thus, an advantage of volumetric heating was demonstrated. The results show that a modest increase in pressure, from 0.05 to 0.3 Torr, caused a one third reduction in primary drying time.

The mathematical model developed in the analytical work relied on the D'Arcy equation to describe the flow of vapor in the porous dried layer. The results of the model confirm trends seen in the measured temperature and weight profiles. Analyzing the effect of varying the chamber pressures shows that lowering the pressure in the range of 1 to 0.01 Torr results in a significant increase in drying rate giving as much as a two thirds reduction in drying time for the case studied. A model incorporating mass transport equations derived from the dusty gas model was also presented. This model offers the benefit of a more accurate prediction of mass transport through the porous dried layer.

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