Related Experiment Video
Updated: Sep 7, 2025
08:59
An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
8.1K
Small scale in vitro method to determine a potential bioequivalent equilibrium solubility range for fed human
Maria Inês Silva1, Ibrahim Khadra1, Kate Pyper2
1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom.
Summary
This study introduces a nine-media system to better predict drug solubility in the fed state intestine. This approach offers a more accurate representation of intestinal drug solubility compared to previous methods.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Biopharmaceutics
- In Vitro Dissolution Science
Background:
- Intestinal drug solubility is crucial for oral absorption, but it varies significantly due to factors like food intake.
- Current in vitro methods using fed human intestinal fluid (FeHIF) or simulated intestinal fluid (SIF) have limitations regarding availability, variability, and lack of consensus on optimal recipes.
- A recent study developed nine simulated fed intestinal fluid (SIF) recipes based on multidimensional characterization of FeHIF, aiming to capture its compositional variability.
Purpose of the Study:
- To measure the equilibrium solubility of thirteen drugs using the nine novel simulated fed intestinal fluid (SIF) recipes.
- To compare the results with previous in vitro dissolution studies, particularly those using design of experiments (DoE) with multiple SIF compositions.
- To evaluate the ability of the nine-media system to accurately reflect the fed intestinal solubility envelope.
Main Methods:
- Equilibrium solubility of thirteen model drugs was determined in nine distinct simulated fed intestinal fluid (SIF) media.
- The solubility data generated was statistically compared against results from previous large-scale (92-media) and small-scale (9-10 media) design of experiments (DoE) studies.
- The influence of biorelevance and media composition on solubility equivalence was analyzed.
Main Results:
- The nine-media system showed improved statistical equivalence with smaller-scale DoE studies compared to a large-scale DoE.
- Selective removal of non-biorelevant compositions from a 92-media DoE enhanced its statistical equivalence to the nine-media system's results.
- Specific drugs like phenytoin and tadalafil exhibited narrow solubility ranges, observable only through the multiple-media approach, highlighting its utility.
Conclusions:
- The nine-media system, derived from multidimensional analysis of fed human intestinal fluid (FeHIF), provides a more representative assessment of the fed intestinal equilibrium solubility envelope.
- Solubility equivalence is influenced by the concentration and composition of media components.
- While the nine-media system demonstrates potential for improved in vitro prediction of intestinal drug solubility, its statistical resolution is insufficient for identifying significant media components.
Related Concept Videos
01:16Methods for Studying Drug Absorption: In vitro
327
In vitro experiments are crucial for understanding the transport and absorption of drugs through biological materials. These studies employ varied methods such as the diffusion cell method, the everted sac technique, and the everted ring technique.
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
327
01:09Methods for Studying Drug Absorption: In situ
342
In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
342
01:21Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH
1.9K
Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
1.9K
01:15Theories of Dissolution: Diffusion Layer Model
899
Dissolution, the process by which drug particles dissolve in a solvent, is explained by the diffusion layer model, a theoretical framework that simulates the absorption of oral drugs and allows us to analyze experimental data.
This process starts with a thin layer, saturated with the drug, forming at the interface between the solid and liquid. The solute then diffuses from this layer into the main solution. The Noyes-Whitney equation suggests that the rate of dissolution relies on the diffusion...
This process starts with a thin layer, saturated with the drug, forming at the interface between the solid and liquid. The solute then diffuses from this layer into the main solution. The Noyes-Whitney equation suggests that the rate of dissolution relies on the diffusion...
899