Dimethyl Fumarate Delayed Release Coating
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Solution Overview
Problem
Dimethyl fumarate in existing pharmaceutical compositions experiences sublimation due to particle sizes below 250 microns, leading to decreased drug content and instability, which affects dissolution and bioavailability.
Innovation Solution
Increasing the particle size of dimethyl fumarate to between 250-950 microns, combined with a two-step coating process involving pre-coating and enteric coating, enhances stability and solubility, ensuring a consistent dissolution profile and mechanical stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If dimethyl fumarate with particle size lower than 250 micron is used, then the dissolution rate is improved, but sublimation occurs leading to decreased drug content and instability
Solution Approach 1:
The patent applies film coating to the dimethyl fumarate particles to create a protective barrier. This thin film coating prevents sublimation of the drug substance while maintaining the particle size and dissolution characteristics. The coating acts as a physical barrier that reduces direct exposure to environmental conditions that cause sublimation.
Solution Approach 2:
The patent changes the particle size parameter of dimethyl fumarate to a specific range (d10: 100-300 μm, d50: 200-400 μm, d90: 300-500 μm). This parameter optimization balances dissolution rate (improved by smaller particles) with sublimation resistance (improved by larger particles), achieving both goals simultaneously through precise particle size control.
2Reliability
If particle size of dimethyl fumarate is increased to reduce sublimation, then stability is improved, but dissolution profile may be affected
Solution Approach 1:
The patent optimizes particle size distribution parameters (d10, d50, d90) to achieve a balance between stability and dissolution. By controlling the distribution rather than using a single size, the patent ensures sufficient surface area for dissolution while maintaining larger overall particle size for reduced sublimation.
Solution Approach 2:
The patent creates a composite structure by coating the dimethyl fumarate particles with a film material. This composite approach combines the benefits of the drug substance with the protective properties of the coating material, achieving both stability and dissolution requirements.
3Ease of manufacture
If particle size is increased to enhance flowability, then manufacturing is improved, but sublimation resistance must be maintained
Solution Approach 1:
The patent specifies particle size parameters (d10: 100-300 μm, d50: 200-400 μm, d90: 300-500 μm) that provide adequate flowability for manufacturing while being large enough to reduce sublimation. The controlled particle size distribution ensures both manufacturability and drug substance stability.
Solution Approach 2:
The film coating provides an additional protective layer that prevents sublimation while the particle size parameters ensure adequate flowability. The coating does not significantly affect flow properties but provides the necessary sublimation resistance.
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 formulation achieves high chemical and mechanical stability, improved bioavailability, and desired dissolution profile by reducing sublimation and maintaining the equivalent dissolution profile of the reference product.
Implementation Method 1
In prior art, dimethyl fumarate has a particle size lower than 250 micron and so occurs the problem of sublimation of dimethyl fumarate
Data Source
AI summary
The present invention is relates to a delayed release pharmaceutical composition comprising dimethyl fumarate and at least one pharmaceutically acceptable excipient.