Mesalamine Tablet pH Buffering for Release Stability
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Solution Overview
Problem
Current mesalamine solid oral dosage forms, particularly controlled and delayed release forms, face challenges in maintaining consistent drug release profiles over time, especially under accelerated storage conditions, leading to premature drug release and fluctuations in therapeutic levels.
Innovation Solution
A solid oral dosage form, preferably a tablet, comprising mesalamine, a controlled release excipient, and a buffering/basifying agent, with an optional enteric coating, designed to provide a consistent release profile over time, even under elevated temperature and humidity conditions, using a blend of mesalamine, controlled release excipient, and buffering/basifying agent, and compressing it into a core with additional pharmaceutical excipients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a controlled release coating is used to provide delayed release of mesalamine, then the drug is released in the target region, but the release profile becomes unstable under accelerated storage conditions leading to premature release
Solution Approach 1:
The patent changes the pH parameter of the microenvironment by adding buffering agents (sodium bicarbonate, calcium carbonate, magnesium hydroxide) to maintain a basic pH of 7.0-8.5. This parameter change stabilizes the controlled release excipient and prevents premature drug release during storage, while maintaining consistent release profiles under accelerated storage conditions
Solution Approach 2:
The patent uses composite materials by combining the controlled release excipient (hydroxypropyl methylcellulose, ethyl cellulose, or polyacrylonitrile) with buffering agents and additional excipients to create a tablet composition that maintains structural integrity and release stability. This composite approach prevents the degradation that causes premature release
2Quantity of substance
If high doses of mesalamine are incorporated into tablets, then therapeutic effectiveness is achieved, but the tablet size increases making it difficult to swallow
Solution Approach 1:
The patent applies a thin enteric coating film to the tablet surface that provides delayed release functionality without significantly increasing tablet size. This coating allows the high-dose tablet to maintain its swallowability while achieving the required therapeutic dosage through efficient drug delivery to the target region
Solution Approach 2:
The patent optimizes the physical parameters of the tablet including compression force, hardness, and size dimensions while incorporating high doses of mesalamine. By carefully controlling these parameters and using appropriate excipients, the tablet maintains a manageable size for swallowing despite containing high drug loads
3Quantity of substance
If multiple dosage forms are administered per day, then adequate dosing is achieved, but patient compliance decreases
Solution Approach 1:
The patent creates a dynamic controlled release system that adjusts drug release over time to maintain therapeutic levels throughout the dosing interval. The controlled release excipient and buffering agent work together to provide sustained release, allowing once-daily dosing while achieving adequate total daily dosage through extended drug availability
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 solution ensures a substantially constant drug release profile before and after storage, maintaining therapeutic levels and reducing adverse effects associated with premature drug release, as demonstrated by similarity factors and release profile stability tests.
Implementation Method 1
a controlled release tablet comprising mesalamine, a controlled release excipient, and a buffering/basifying agent wherein the release of the mesalamine from the controlled release tablet is substantially constant when stored for a period of time including under accelerated storage conditions
Data Source
AI summary
Solid oral mesalamine delayed/controlled release tablets with storage stable dissolution profiles are described.