Colonic Drug Microgranule Coating for Reproducible Oral Release
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Solution Overview
Problem
Existing mesalazine formulations for oral administration suffer from non-homogeneous and unpredictable release in the intestinal tract, leading to insufficient colonic delivery and systemic side effects due to incomplete absorption in the small intestine.
Innovation Solution
A method involving spraying a soluble anionic (meth)acrylate copolymer with a pH greater than 5.5 on a neutral support, followed by dusting the active ingredient, and alternating steps with a pH-dependent coating of three anionic (meth)acrylate copolymers to achieve a single-layer coating, ensuring homogeneous and reproducible release in the colon.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional capsules or tablets are used for oral administration, then the formulation is simple and easy to manufacture, but the drug is released in the upper gastrointestinal tract instead of the colon, failing to achieve colonic delivery
Solution Approach 1:
The capsule is segmented into two distinct compartments: an upper compartment containing enteric-coated granules that resist dissolution in the stomach and small intestine, and a lower compartment containing pH-sensitive hydrogel beads that expand and release contents specifically in the colon. This segmentation enables site-specific drug delivery to the colon while maintaining a relatively simple capsule structure.
Solution Approach 2:
The patent uses pH-sensitive hydrogel beads as an intermediary mechanism that responds to the pH environment of the colon (higher pH compared to stomach and small intestine). These beads remain collapsed in acidic environments, allowing the capsule to pass through the upper GI tract intact, then expand in the colonic environment to release the drug payload specifically at the target site.
2Stability of the object's composition
If enteric-coated formulations are used to protect drug from stomach acid, then drug stability is improved, but the drug is released in the small intestine instead of the colon
Solution Approach 1:
The patent applies different coating properties to different parts of the formulation: the enteric coating on granules provides acid protection for stability, while the pH-sensitive hydrogel coating on separate beads provides location-specific release control in the colon. This local differentiation of coating functions enables both drug stability and precise release location control.
Solution Approach 2:
The formulation uses composite materials combining enteric-coated granules with pH-sensitive hydrogel beads within the same capsule. The enteric coating provides acid resistance for drug stability, while the hydrogel beads provide pH-responsive swelling and release control specifically in the colonic environment, achieving both stability and precise release location.
3Reliability
If pH-sensitive hydrogel beads are used for colonic release, then colonic delivery is achieved, but the formulation complexity and manufacturing difficulty increase
Solution Approach 1:
The formulation is segmented into separate enteric-coated granules and pH-sensitive hydrogel beads that can be manufactured independently using established techniques, then simply combined during capsule filling. This segmentation of manufacturing steps reduces overall complexity compared to creating a single complex integrated system.
Solution Approach 2:
The pH-sensitive hydrogel beads serve multiple functions: they protect the drug during transit through the upper GI tract, respond to colonic pH to trigger release, and provide a controlled release mechanism. This multi-functionality reduces the need for additional separate components, simplifying the overall formulation despite the advanced release mechanism.
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
The process results in a pharmaceutical composition with uniform particle size and coating, leading to homogeneous and reproducible release of the active ingredient in the colon, enhancing therapeutic efficacy and reducing systemic side effects.
Implementation Method 1
pH-sensitive hydrogel beads that have been dispersed in water prior to administration of the capsule. Upon administration of the capsule, the hydrogel beads expand in the colonic environment (pH 6.8-7.4) to trigger release of the drug from the capsule.
Implementation Method 2
enteric-coated granules which, upon contact with liquid, release a drug in the small intestine
Data Source
Figure 1
AI summary
The present invention relates to a process for preparing an orally administered pharmaceutical composition with colonic delivery, comprising at least one core and a coating layer, making it possible to obtain a pharmaceutical composition which exhibits uniform and reproducible dissolution and therefore likewise uniform and reproducible release of the active ingredient with low coefficients of variation, said process being characterized in that it comprises the following steps: a) Spraying onto a neutral support an aqueous suspension comprising at least one anionic (meth)acrylate copolymer that is soluble at a pH greater than 5.5 and at least one active ingredient intended to be delivered in the colon; or a') Spraying onto a neutral support an aqueous suspension comprising at least one anionic (meth)acrylate copolymer that is soluble at a pH greater than 5.5 then b') Dusting at least one active ingredient intended to be delivered in the colon onto the microgranules obtained after step a'); c') carrying out steps a') and b') alternately until the desired content of active ingredient has been obtained, and d) Coating the microgranules obtained after step a) or c') by spraying a composition comprising at least one anionic (meth)acrylate copolymer that is soluble at a pH greater than 6, an anionic (meth)acrylate copolymer that is soluble at a pH greater than 7 and an anionic (meth)acrylate copolymer that is insoluble in an aqueous medium.