Approximately 80% of pharmaceutical products and the ingredients required for their manufacture are in powder form. The solid dosage form (tablets and capsules) is manufactured by either dry-blending of fine powder ingredients or combining the ingredients in a wet granulation step, followed by drying. Arching, ratholing, caking, segregation and flooding are some of the commonly encountered flow problems in the handling of fine powders. These problems lead to losses worth thousands of dollars at production scale. Poor powder flowability is a consequence of the combined effects of many variables, including improper equipment design, particle size, size distribution, shape, moisture content and surface texture. In the present work, a systematic study has been performed to determine the relationship between the flowability of fine powders and their physical properties of mean size and size distribution, density and shape.<p> Flowability studies were done on six different powders: the NutraSweet® Brand sweetener (aspartame), Respitose ML001, Alpha-D-Lactose monohydrate, the pharmaceutical binder Methocel (R) F50 Premium Hydroxypropyl methylcellulose- HPMC, a placebo pharmaceutical granulate, and common pastry flour. Scanning electron microscopy (SEM) and stereomicroscopy were used for particle shape and size analysis. Particle size distribution was determined using the laser light scattering technique. Powder flowability was measured using shear strength, angle of repose, and tapped-to-bulk density measurements. A novel method of measuring the dynamic angle of repose using electrical capacitance tomography (ECT) was developed. <p> Analysis of the images from microscopy revealed that the particles of aspartame and HPMC powders were elongated, the particles of ML001, pastry flour and lactose monohydrate powders were irregular, and the particles of placebo granulate were nearly spherical. Particle size was found to be the most reliable indicator of powder flowability, with decreasing particle size corresponding to lower flowability; however other parameters such as particle elongation and irregularity, were also found to have an influence on powder flowability. Although HPMC and pastry flour had similar particle sizes, they exhibited differences in flowability. This can be explained by the greater irregularity of the flour particles. Particle irregularity may cause mechanical interlocking between the particles, thus reducing powder flowability. ECT was found to be a promising non-intrusive tool for the measurement of the dynamic angle of repose. Unlike other methods for the measurement of dynamic angle of repose, the results obtained from ECT were not influenced by the effect of end caps. The present technique could be used by pharmaceutical industries in process analytical technology (PAT) for the detection and elimination of potential flow problems early in the manufacturing process.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:SSU.etd-07032006-115722 |
| Date | 03 July 2006 |
| Creators | Bodhmage, Abhaykumar Krishnarao |
| Contributors | Wang, Hui, Sharma, Jitendra, Pugsley, Todd |
| 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-07032006-115722/ |
| 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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