As part of the production of certain solid-dosage pharmaceuticals, granulated ingredients are dried in a batch fluidized bed dryer. Currently, the determination of the completion of the drying process is accomplished through measurements of product or outlet air temperatures. No quantitative measurement of hydrodynamic behaviour is employed. Changes in bed hydrodynamics caused by variations in fluidization velocity may lead to increased particle attrition. In addition, excessive desiccation of the granules caused by inaccurate determination of the drying endpoint may lead to an increase in the thermal and mechanical stresses within the granules. The activity of future high-potency or peptide based drug products may be influenced by these effects. Therefore, the quantification of hydrodynamic changes may be a key factor in the tighter control of both fluidization velocity and product moisture, which are critical for maintaining product quality. <p>High-frequency measurements of pressure fluctuations in a batch fluidized bed dryer containing pharmaceutical granulate have been used to provide a global, non-intrusive indication of the hydrodynamic changes occurring throughout the drying process. A chaotic attractor comparison statistical test known as the S-statistic, has been applied to quantify these changes in drying and a related unit operation, fluidized bed granulation. The S-statistic showed a sensitivity to moisture which is not seen with frequency and amplitude analysis. In addition, the S-statistic has been shown to be useful in identifying an undesirable bed state associated with the onset of entrainment in a bed instrumented for the collection of both pressure fluctuation and entrainment data. Thus, the use of the S-statistic analysis of pressure fluctuations may be utilized as a low-cost method for determining product moisture or changes hydrodynamic state during fluidized bed drying. <p>Electrical capacitance tomography (ECT) has also been applied in this study to image the flow structure within a batch fluidized bed used for the drying of pharmaceutical granulate. This represents the first time that ECT has been applied to a bed of wet granulate material. This was accomplished through the use of a novel dynamic correction technique which accounts for the significant reduction in electrical permittivity occurring as moisture is lost during the drying process. The correction has been independently verified using x-ray tomography. <p>Investigation of the ECT images taken in the drying bed indicates centralized bubbling behaviour for approximately the first 5 minutes of drying. This behaviour is a result of the high liquid loading of the particles at high moisture. Between moisture contents of 18-wt% and 10-wt%, the tomograms show an annular pattern of bubbling behaviour with a gradual decrease in the cross-sectional area involved in bubbling behaviour. The dynamic analysis of this voidage data with the S-statistic showed that a statistically significant change occurs during this period near the walls of the vessel, while the centre exhibits less variation in dynamic behaviour. The changes identified by the S-statistic analysis of voidage fluctuations near the wall were similar to those seen in the pressure fluctuation measurements. This indicates that the source of the changes identified by both these measurement techniques is a result of the reduction in the fraction of the bed cross-section involved in bubbling behaviour. At bed moisture contents below 5-wt%, rapid divergence was seen in the S-statistic applied to both ECT and pressure fluctuation measurements. This indicates that a rapid change in dynamics occurs near the end of the drying process. This is possibly caused by the entrainment of fines at this time, or the build-up of electrostatic charge. <p>The use of the complimentary pressure fluctuation and ECT measurement techniques have identified changes occurring as a result of the reduction of moisture during the drying process. Both the localized changes in the voidage fluctuations provided by the ECT imaging and the global changes shown by the pressure fluctuation measurements indicate significant changes in the dynamic behaviour caused by the reduction of moisture during the drying process. These measurement techniques could be utilized to provide an on-line indication of changes in hydrodynamic regime. This information may be invaluable for the future optimization of the batch drying process and accurate determination of the drying endpoint.
Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:SSU.etd-03222005-144527 |
Date | 24 March 2005 |
Creators | Chaplin, Gareth Edgar |
Contributors | Winters, Conrad, van Ommen, Ruud, Torvi, David A., Pugsley, Todd, Lin, Yen-Han, Hill, Gordon A., Dalai, Ajay K. |
Publisher | University of Saskatchewan |
Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
Language | English |
Detected Language | English |
Type | text |
Format | application/pdf |
Source | http://library.usask.ca/theses/available/etd-03222005-144527/ |
Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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