In Vitro Intestinal Drug Disposition Device with Segmented Chambers
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Solution Overview
Problem
Current in vitro lipolysis studies for evaluating lipid-based formulations (LBFs) provide poor in vitro-in vivo correlation (IVIVC) due to the need for expensive, time-consuming in vivo experiments or separate in vitro and ex vivo studies, and they often result in drug precipitation issues.
Innovation Solution
An in vitro intestinal drug disposition device with a donor chamber and a receiver chamber separated by an absorption membrane, mimicking the intestinal environment and blood system, allowing simultaneous study of digestion and absorption processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If in vitro lipolysis studies are conducted using traditional single-chamber vessels, then the digestion process can be studied, but the in vitro-in vivo correlation remains poor and drug precipitation occurs
Solution Approach 1:
The device is divided into two separate chambers (donor chamber and receiver chamber) connected by an absorption membrane. This segmentation allows the digestion process to occur in the donor chamber while simultaneously enabling absorption studies in the receiver chamber, thereby improving in vitro-in vivo correlation and preventing drug precipitation by maintaining a concentration gradient across the membrane.
2Reliability
If separate in vitro and ex vivo experiments are conducted to evaluate LBF performance, then comprehensive data can be obtained, but the process becomes time-consuming and expensive
Solution Approach 1:
The device combines in vitro digestion and absorption studies into a single integrated experimental system. The donor chamber accommodates LBFs and digestive enzymes for lipolysis, while the receiver chamber simultaneously performs absorption studies through the absorption membrane, eliminating the need for separate ex vivo experiments and significantly reducing time and cost.
3Quantity of substance
If the donor chamber has a large volume to accommodate digestion, then sufficient digestion medium is available, but the surface area to volume ratio decreases reducing absorption efficiency
Solution Approach 1:
The donor chamber is designed with a conical shape that creates localized regions with different properties. The smaller cross-sectional area at the top creates a region with higher surface area to volume ratio near the absorption membrane, optimizing absorption efficiency, while the overall chamber volume remains sufficient to accommodate the required digestion medium volume.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This setup enhances biorelevance and reduces drug precipitation by maintaining a concentration gradient, improving IVIVC and allowing efficient testing of LBFs and other compounds without the need for costly in vivo experiments.
Implementation Method 1
an absorption membrane arranged in between and separating the donor chamber and the receiver chamber. A first main side of the absorption membrane is configured to be in contact with the donor solution and a second, opposite main side of the absorption membrane is configured to be in contact with the absorption solution
Data Source
AI summary
An in vitro intestinal drug disposition device (1) comprises a donor chamber (2) for a donor solution and having a bottom end (18) and a top end (19). The device (1) also comprises a receiver chamber (3) for an absorption solution and an absorption membrane (4) arranged in between and separating the chambers (2, 3). A first side (5) of the absorption membrane (4) is to be in contact with the donor solution and a second side (6) of the absorption membrane (4) is to be in contact with the absorption solution. A ratio of an internal volume of the donor chamber (2) to an area of the first membrane side (5) is equal to or smaller than 3 ml/cm2. A cross-sectional area of the donor chamber (2) at the bottom end (18) is larger than a cross-sectional area of the donor chamber (2) at the top end (19).