Thesis
Evaluating the fed state impact on drug solubility and absorption : a biorelevant in vitro approach
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2025
- Thesis identifier
- T17294
- Person Identifier (Local)
- 202090909
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Biopharmaceutics, which studies the relationship between a drug's physical, chemical, biological, and pharmacological properties and its dosage form, is essential for studying and optimising oral formulations. This thesis explores solubility and dissolution behaviours of drugs using fed and fasted state biorelevant media systems with nine media recipes each, derived from a multidimensional analysis of human intestinal fluids. The central hypothesis of this thesis is that applying biorelevant media to biopharmaceutical testing can provide improved insights on drug absorption. To test this hypothesis, Chapter 2 describes the preparation of fasted and fed biorelevant simulated media, as well as the methods to apply these media to measure drug solubility, dissolution and supersaturation. Chapter 3 compares two approaches for measuring drug solubility in fed state media: multidimensional analysis and Design of Experiments. Chapter 4 then applies fed state solubility data to a novel Developability Classification System grid, examining population-level variability in solubility. In Chapter 5 solubility behaviour is analysed to identify patterns that reduce the number of media measurements needed for fed state solubility profiling. Chapter 6 explores the in vitro/in vivo correlation between fasted and fed biorelevant media systems solubility data and published fasted and fed human intestinal solubility values, establishing the potential for the biorelevant system as a bioequivalent model. Chapter 7 introduces a tool for predicting food effects on drug absorption using solubility measurements and Solubility Limited Absorbable Dose calculations. Finally, Chapter 8 investigates the impact of media changes on intrinsic dissolution rate and supersaturation, providing new insights into how biorelevant media conditions affect dissolution and supersaturation behaviours in both fasted and fed states. This thesis makes significant contributions for biopharmaceutics by expanding the limited data available on drug behaviour in the fed state and it uncovers variations in drug solubility and dissolution that single media methods fail to reveal, offering deeper insights into drug performance in more realistic gastrointestinal conditions.
- Advisor / supervisor
- Khadra, Ibrahim
- Resource Type
- DOI
Beziehungen
Objekte
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PDF of thesis T17294 | 2025-06-13 | Öffentlich | Herunterladen |