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Updated: Oct 23, 2025
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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
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Small scale in vitro method to determine a bioequivalent equilibrium solubility range for fasted human intestinal
Qamar Abuhassan1, Ibrahim Khadra1, Kate Pyper2
1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom.
Summary
Assessing drug solubility in the intestine is challenging. This study uses nine bioequivalent simulated intestinal fluid (SIF) media to accurately determine drug solubility ranges, improving in vivo predictions.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Biopharmaceutical Sciences
- Analytical Chemistry
Background:
- Drug solubility is critical for oral absorption, but in vitro assessment of intestinal solubility is difficult.
- Human intestinal fluid (HIF) is variable and hard to obtain; simulated intestinal fluids (SIF) are alternatives, but optimal recipes are unknown.
- A prior study identified nine bioequivalent SIF media recipes representing over 90% of HIF variability.
Purpose of the Study:
- To apply nine bioequivalent SIF media recipes to determine the equilibrium solubility of twelve model drugs.
- To compare these solubility measurements with previous statistical design of experiment (DoE) data and literature values.
- To evaluate the ability of a reduced set of SIF media to represent the intestinal solubility envelope.
Main Methods:
- Equilibrium solubility of twelve drugs was determined using nine bioequivalent SIF media recipes.
- Results were compared statistically to a previous DoE study and literature data for fasted HIF and SIF.
- Analysis considered the solubility range and behavior of specific drugs (phenytoin, tadalafil, griseofulvin).
Main Results:
- Bioequivalent solubility measurements were statistically equivalent to previous DoE results and encompassed literature values.
- The measured solubility range was narrower than previous DoE studies, suggesting improved in vivo equivalence.
- Three drugs exhibited narrow solubility ranges, consistent with their molecular properties, highlighting the value of range measurements.
Conclusions:
- A small set of bioequivalent SIF media can effectively assess the fasted intestinal equilibrium solubility envelope.
- This approach provides a more representative solubility range compared to previous DoE studies, enhancing in vivo prediction.
- Intestinal drug solubility is best represented as a range, not a single value, influenced by media composition.
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