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 <i>in vivo</i> 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 <i>in
vivo</i> performance.
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/11317124 |
| Date | 04 December 2019 |
| Creators | Ahmed H. a. a. Elkhabaz (8071994) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/Characterization_of_the_Phase_Behavior_of_Supersaturated_Solutions_in_Simulated_and_Aspirated_Human_Fluids/11317124 |
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