Colesevelam Gastro-Resistant Composition for Lower-GI Bile Acid Binding
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Solution Overview
Problem
Current bile acid sequestrants for treating bile acid malabsorption and diarrhea have low patient compliance due to high doses, adverse reactions, and unwanted interactions in the upper GI tract, leading to nutritional deficiencies and drug interactions.
Innovation Solution
A pharmaceutical composition with a high drug load of colesevelam or its salt, coated for gastro-resistant release primarily in the ileum and colon, reducing the number of daily administrations and minimizing interference with bile acid function and drug absorption.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high doses of bile acid sequestrants are administered to treat bile acid malabsorption, then therapeutic effectiveness is improved, but patient compliance deteriorates due to frequent administration and adverse reactions
Solution Approach 1:
The patent divides the bile acid sequestrant treatment into targeted segments: the gastro-resistant coating segments the release location to the lower GI tract (ileum/colon), while the high drug load segments the dosage frequency. This segmentation allows the medication to act specifically where needed (colon for bile acid malabsorption) while reducing unnecessary exposure in the upper GI tract, thereby maintaining effectiveness while improving compliance.
Solution Approach 2:
The patent applies local quality by concentrating the sequestrant action specifically in the lower gastrointestinal tract where bile acid malabsorption occurs. The gastro-resistant coating ensures the drug is released primarily in the ileum and colon rather than throughout the entire GI tract. This localized action maintains therapeutic effectiveness at the target site while reducing adverse effects in other areas, thereby improving patient compliance.
2Speed
If bile acid sequestrants are released in the upper GI tract, then drug absorption is rapid, but unwanted interactions with food and other drugs occur leading to nutritional deficiencies
Solution Approach 1:
The patent applies preliminary action by pre-coating the bile acid sequestrant with a gastro-resistant coating before administration. This coating prevents premature release and interactions in the upper GI tract. The drug is designed to maintain its integrity through the stomach and duodenum, only releasing its active ingredient when it reaches the lower GI tract, thereby avoiding harmful interactions with food and other medications while still achieving rapid absorption at the target site.
Solution Approach 2:
The gastro-resistant coating acts as an intermediary between the bile acid sequestrant and the upper GI tract environment. This coating layer prevents direct contact and interaction between the sequestrant and food or other drugs in the stomach and duodenum. The intermediary coating allows the drug to pass through the upper GI tract unchanged, then releases the active ingredient in the lower GI tract where rapid absorption occurs without harmful interactions.
3Reliability
If multiple tablets are administered daily to achieve therapeutic dose, then adequate bile acid binding is achieved, but treatment complexity increases
Solution Approach 1:
The patent applies merging by combining a high concentration of bile acid sequestrant (high drug load) into a single tablet formulation. By incorporating a large amount of active ingredient (e.g., cholestyramine, colestipol, or colesevelam) into one tablet with gastro-resistant properties, the patent merges multiple dosing requirements into a single administration that can provide adequate bile acid binding throughout the lower GI tract, thereby reducing treatment regimen complexity while maintaining binding efficacy.
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
Enhances patient compliance by reducing the frequency of doses and targeting excess bile acids in the colon, while minimizing nutritional deficiencies and drug interactions.
Implementation Method 1
a gastro-resistant coating covering the tablet core
Implementation Method 2
bile acid sequestrants...colesevelam...binding to bile acids
Data Source
Figure 1
AI summary
Pharmaceutical compositions comprising bile acid sequestrants, their use in treating bile acid malabsorption, and associated conditions such as bile acid diarrhea and colitis are described herein. Methods for treating bile acid malabsorption and associated conditions are also described.