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Dissertation
Understanding the stress-induced phase transformation of chlorpropamide (CPM) in tablet compaction
Doctor of Philosophy (Ph.D.), Drexel University
Nov 2024
DOI:
https://doi.org/10.17918/00010860
Abstract
During tablet compaction, a crystalline form of active pharmaceutical ingredients (APIs) may transform into another crystalline state (polymorph) depending on the local stresses. This phenomenon presents a major challenge during R&D stages and poses regulatory risks to new drug applications. Over the past years, compression-induced phase transformation of Chlorpropamide from form C (CPM-C) to form A (CPM-A) has attracted attention; however, current understanding remains limited and a comprehensive framework to describe this phenomenon is still elusive. Prior studies on the polymorphic transformations in CPM-C tablet typically reported conversion percentages as a function of applied compaction pressure. Recent studies have suggested the possibility of local variation in the transformation due to wall friction, but they had unclear explanations of the frictional contribution to this phenomenon. In this work, a methodology was developed to map the phase transformation throughout the cross surface of a split tablet. The effect of tablet shape and frictional conditions on the distribution of local conversion was investigated. Additionally, we identified the particle plastic deformation of CPM-C that serves as fundamental driving force behind its transformation. Our work sheds new light on the problem of phase transformation during compaction, offering an enhanced understanding that can be beneficial in optimizing formulations as this phenomenon arises during pharmaceutical R&D.
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Details
- Title
- Understanding the stress-induced phase transformation of chlorpropamide (CPM) in tablet compaction
- Creators
- Phuong Duc Bui
- Contributors
- Antonios Zavaliangos (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiv, 109 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Materials (Science and) Engineering (Metallurgical Engineering) [Historical]; College of Engineering (1970-2026); Drexel University
- Other Identifier
- 991022020016904721