Aminosalicylate Microparticles Enteric Coating
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Solution Overview
Problem
There is a need for liquid pharmaceutical compositions for the oral administration of aminosalicylates, which are anti-inflammatory drugs used to treat inflammatory bowel disease, as current dosage forms are primarily solid and do not provide effective local activity at the desired site of action in the colon or small bowel.
Innovation Solution
The development of oral liquid pharmaceutical compositions comprising extended release aminosalicylate microparticles with an enteric delayed release coating, suspended in an aqueous liquid carrier, designed to release the drug effectively in the gastrointestinal tract, specifically formulated to deliver mesalazine or other aminosalicylates to the lower gastrointestinal tract over a therapeutic period.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If solid dosage forms are used for aminosalicylate administration, then manufacturing and storage are simplified, but effective local delivery to the colon or small bowel is not achieved
Solution Approach 1:
The invention segments the dosage form into microparticles (1-250 μm) with controlled release properties, suspended in a liquid carrier. This segmentation allows the complex release mechanism to be achieved at the particle level while maintaining a simple liquid dosage form, resolving the contradiction between reliable target site delivery and dosage form complexity
Solution Approach 2:
The invention changes the physical state from solid to liquid suspension, and controls drug release by changing particle size parameters (1-250 μm) and using pH-sensitive polymers that change properties at different pH levels. This allows effective colon delivery through parameter control rather than complex dosage form design
2Reliability
If immediate release formulations are used, then drug availability is rapid, but therapeutic effect at the colon is reduced due to premature release in the stomach
Solution Approach 1:
The microparticles are pre-coated with pH-sensitive polymers (such as Eudragit®) that remain intact in the acidic stomach environment and only dissolve at the higher pH of the intestine. This preliminary protective action ensures the drug is released at the correct location without premature release, maintaining both reliability and timing
Solution Approach 2:
The pH-sensitive polymer coating acts as an intermediary between the drug and the gastrointestinal environment. It protects the drug from premature release in the stomach while allowing controlled release in the intestine, resolving the contradiction between rapid availability and target site delivery
3Duration of action of moving object
If extended release mechanisms are implemented, then therapeutic duration is prolonged, but manufacturing precision and coating uniformity become more difficult to achieve
Solution Approach 1:
The invention applies different properties to different parts of the dosage system: the microparticles have extended release properties through their size and composition, while the liquid carrier provides immediate availability. This local differentiation achieves prolonged therapeutic duration without requiring uniform coating across the entire dosage form, reducing manufacturing precision requirements
Solution Approach 2:
The invention uses composite microparticles combining drug, pH-sensitive polymers, and extended release materials in a liquid suspension matrix. This composite approach achieves extended release functionality through material composition rather than complex manufacturing processes, maintaining both therapeutic duration and manufacturing feasibility
4Ease of operation
If liquid formulations are developed, then patient compliance and absorption are improved, but stability and shelf life become compromised
Solution Approach 1:
The microparticles act as flexible containment structures that protect the drug in liquid suspension. The pH-sensitive polymer coatings on these particles maintain stability in the liquid formulation while allowing controlled release, resolving the contradiction between liquid formulation benefits and stability requirements
Solution Approach 2:
The invention controls formulation stability by adjusting particle size parameters (1-250 μm) and using pH-sensitive polymers that change properties at different pH levels. These parameter changes ensure the liquid formulation remains stable during storage while maintaining patient compliance advantages
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 compositions exhibit a controlled release profile, with minimal drug release at acidic pH and substantial release at intestinal pH, ensuring effective delivery to the target site, maintaining stability for at least two years and maintaining therapeutic efficacy with minimal degradation.
Implementation Method 1
an outer delayed release coating provided with a pH-dependent solubility
Implementation Method 2
a plurality of extended release aminosalicylate microparticles
Data Source
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AI summary
Described herein are oral liquid pharmaceutical compositions for the oral administration of an aminosalicylate, as well as methods of making such oral liquid pharmaceutical compositions, and therapeutic methods for using them. The oral liquid pharmaceutical compositions comprise extended-release microparticles formulated with an aminosalicylate, wherein the extended-release microparticles are provided with an outer delayed release coating.