Purdue University Graduate School
Elkhabaz Dissertation.pdf (6.38 MB)

Characterization of the Phase Behavior of Supersaturated Solutions in Simulated and Aspirated Human Fluids

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posted on 2019-12-04, 18:53 authored by Ahmed H. a. a. ElkhabazAhmed H. a. a. Elkhabaz
Supersaturating formulations have become a popular approach for enhancing the oral bioavailability of poorly water-soluble drugs. These formulation strategies can increase the intraluminal concentration by generating and maintaining supersaturation, which provides an enhanced driving force for in vivo absorption. Due to their inherent metastability however, crystallization in these systems can occur, negatively impacting their bioperformance. Therefore, it is critical to characterize the phase behavior and crystallization tendency of supersaturated solutions under biorelevant conditions in order to assess their potential for maximized oral absorption. Biorelevant media are commonly employed to simulate the presence of bile salts and phospholipids found in the human intestinal fluids. Currently, there is little knowledge of how simulated and aspirated intestinal media can impact the complex phase behavior of supersaturated solutions. More importantly, commonly-used simulated media rely on oversimplified recipes in terms of bile salt composition. As a result, comprehensive understanding of how well simulated media correlate with aspirated media with respect to supersaturation stability and phase transition outcomes, is still lacking. The work presented within this thesis aims to address the knowledge gap by assessing the phase behavior of supersaturated solutions using complementary analytical approaches. Depending on the type of medium used to evaluate supersaturation, variations in solubility, supersaturation thermodynamics and crystallization kinetics can be observed. This understanding can aid future efforts to optimize simulated media, design supersaturating formulations and predict their in vivo performance.


Degree Type

  • Doctor of Philosophy


  • Industrial and Physical Pharmacy

Campus location

  • West Lafayette

Advisor/Supervisor/Committee Chair

Lynne S. Taylor

Additional Committee Member 2

Garth J. Simpson

Additional Committee Member 3

Gregory T. Knipp

Additional Committee Member 4

Qi (Tony) Zhou

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