Theoretical and experimental investigation of particle interactions in pharmaceutical powder blending
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2007.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2008
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| Online Access: | http://dspace.mit.edu/handle/1721.1/38962 http://hdl.handle.net/1721.1/38962 |
| _version_ | 1826195457857028096 |
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| author | Pu, Yu, Ph. D. Massachusetts Institute of Technology |
| author2 | Charles L. Cooney. |
| author_facet | Charles L. Cooney. Pu, Yu, Ph. D. Massachusetts Institute of Technology |
| author_sort | Pu, Yu, Ph. D. Massachusetts Institute of Technology |
| collection | MIT |
| description | Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2007. |
| first_indexed | 2024-09-23T10:12:59Z |
| format | Thesis |
| id | mit-1721.1/38962 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T10:12:59Z |
| publishDate | 2008 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/389622019-04-11T14:22:25Z Theoretical and experimental investigation of particle interactions in pharmaceutical powder blending Pu, Yu, Ph. D. Massachusetts Institute of Technology Charles L. Cooney. Massachusetts Institute of Technology. Dept. of Chemical Engineering. Massachusetts Institute of Technology. Dept. of Chemical Engineering. Chemical Engineering. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2007. Includes bibliographical references. In pharmaceutical manufacturing practices, blending of active pharmaceutical ingredient (API) with excipients is a crucial step in that homogeneity of active ingredient after blending is a key issue for the quality assurance of final products. Inadequate knowledge of the interdependence between raw material properties and their impact on the blending process often gives rise to product variance and failure and therefore higher manufacturing costs. Since particles are the basic unit of powder flow, a fundamental understanding of the crucial particle characteristics and particle interactions is essential for a good prediction and control of the blending process. In this work, inter-particle adhesion forces including van der Waals force, capillary force and electrostatic force of lactose monohydrate and microcrystalline cellulose were measured by the atomic force microcopy and other techniques. Their correlations with particle properties and environmental variables were elucidated quantitatively through mathematical modeling, and their impacts on powder blending homogeneity were investigated experimentally. It was found that surface roughness, electrostatic surface charges, moisture sensitivity as well as relative humidity are crucial parameters to determine inter-particle adhesion forces. (cont.) By controlling these factors, the inter-particle adhesion forces can be optimized to improve final blend homogeneity. For instance, using excipient particles processed with surface-smoothing method reduced the blending time to reach endpoint. It was also found that enhancing electrostatic attractive interactions between excipient and API particles resulted in better blend homogeneity. In addition, the mathematical force models developed in this study allowed us to predict the magnitudes of inter-particle adhesion forces, which can be later used as an important input parameter in simulating the powder blending process of different scales. The mechanistic knowledge of particle interactions and their dependence on particle properties through this study provides a theoretical foundation for a successful linkage between the micro-scale particle level and the macro-scale bulk powder flow behavior, enhances process understanding, and opens opportunities for process improvement. by Yu Pu. Ph.D. 2008-11-10T19:52:27Z 2008-11-10T19:52:27Z 2007 2007 Thesis http://dspace.mit.edu/handle/1721.1/38962 http://hdl.handle.net/1721.1/38962 166327705 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/38962 http://dspace.mit.edu/handle/1721.1/7582 142 p. application/pdf Massachusetts Institute of Technology |
| spellingShingle | Chemical Engineering. Pu, Yu, Ph. D. Massachusetts Institute of Technology Theoretical and experimental investigation of particle interactions in pharmaceutical powder blending |
| title | Theoretical and experimental investigation of particle interactions in pharmaceutical powder blending |
| title_full | Theoretical and experimental investigation of particle interactions in pharmaceutical powder blending |
| title_fullStr | Theoretical and experimental investigation of particle interactions in pharmaceutical powder blending |
| title_full_unstemmed | Theoretical and experimental investigation of particle interactions in pharmaceutical powder blending |
| title_short | Theoretical and experimental investigation of particle interactions in pharmaceutical powder blending |
| title_sort | theoretical and experimental investigation of particle interactions in pharmaceutical powder blending |
| topic | Chemical Engineering. |
| url | http://dspace.mit.edu/handle/1721.1/38962 http://hdl.handle.net/1721.1/38962 |
| work_keys_str_mv | AT puyuphdmassachusettsinstituteoftechnology theoreticalandexperimentalinvestigationofparticleinteractionsinpharmaceuticalpowderblending |