Multi-layer pH-dependent colon targeting formulation
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Solution Overview
Problem
Current pH-dependent release systems for active ingredients in the large intestine are unreliable due to interindividual variability in intestinal pH values, leading to potential early, late, or absent release, with a narrow operating range that does not account for pH fluctuations in the small intestine.
Innovation Solution
A formulation with multiple layers, where each layer is designed to dissolve or become permeable at specific pH values, allowing for a controlled release of active ingredients by sequentially exposing them to increasing pH values, ensuring release only upon a sufficient pH drop after stomach passage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a pH-dependent coating is used to trigger release in the large intestine, then release can be initiated when pH exceeds a threshold value, but the narrow operating range (about 0.5 pH units) makes the system unreliable due to interindividual variability in intestinal pH values
Solution Approach 1:
The coating is divided into multiple functional layers with different pH thresholds: an outer enteric layer that dissolves at higher pH (above 7) and an inner cecal layer that dissolves at lower pH (below 6.5). This segmentation allows the formulation to adapt to a broader range of intestinal pH conditions while maintaining reliable release in the large intestine.
Solution Approach 2:
The system uses multiple pH threshold parameters instead of a single threshold. By incorporating layers with different pH solubility characteristics, the formulation can respond to varying pH conditions across different individuals while ensuring release occurs within the target pH range of the large intestine.
2Adaptability or versatility
If the threshold of solubility of the anionic polymer is lowered to achieve release in cases with lower pH values, then release can occur with more individuals, but release may occur too early in individuals with higher pH values
Solution Approach 1:
The coating is divided into multiple functional layers with different pH thresholds: an outer enteric layer that dissolves at higher pH (above 7) and an inner cecal layer that dissolves at lower pH (below 6.5). This segmentation allows the formulation to adapt to a broader range of intestinal pH conditions while maintaining reliable release in the large intestine.
Solution Approach 2:
The enteric layer acts as a preliminary barrier that must be dissolved first before the cecal layer is exposed to intestinal fluids. This preliminary action ensures that even when the inner layer's pH threshold is lowered to accommodate variable pH conditions, the outer layer prevents premature release and ensures release occurs only when appropriate conditions are met.
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 approach expands the operating range for reliable release in the large intestine, reducing the risk of premature or delayed release and accommodating pH fluctuations, ensuring consistent delivery of active ingredients.
Implementation Method 1
each layer is designed to dissolve or become permeable at specific pH values
Data Source
AI summary
The present invention relates to a formulation for the controlled release of active ingredients after the passage of the ileo-cecal-valve, comprising one or more active ingredients or one or more active ingredient containing cores (W), enveloped by one or more envelopments (C), which are dissoluble or permeable above an individual defined pH value and are dissoluble or permeable below another individual defined pH value, again enveloped by an envelopment (E), which is dissoluble or permeable above still another individual defined pH value.