Dimethyl Fumarate Compositions for Photodegradation and Oxidation Control
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Solution Overview
Problem
Dimethyl fumarate is susceptible to photodegradation and oxidation, leading to the formation of undesirable impurities that can affect its therapeutic efficacy, particularly in pharmaceutical compositions used for treating conditions like multiple sclerosis and psoriasis.
Innovation Solution
The development of pharmaceutical compositions that limit the presence of specific impurities, such as compounds of Formula (I), (II), (III), (IV), (V), and (VI), to less than 2-15 ppm or 0.1-3% by weight based on the total weight of dimethyl fumarate, and avoid destabilizing agents like polyvinyl pyrrolidones, polyethylene glycols, and polysorbate surfactants, ensuring stability and effectiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dimethyl fumarate is used in pharmaceutical compositions, then therapeutic efficacy for treating multiple sclerosis and psoriasis is achieved, but photodegradation and oxidation occur leading to formation of undesirable impurities
Solution Approach 1:
The patent applies inert atmosphere by excluding oxygen and moisture from the pharmaceutical composition through the use of enteric coating and controlled packaging, preventing oxidation and hydrolysis of dimethyl fumarate that would otherwise generate impurities like dimethyl oxalate and methyl formate
Solution Approach 2:
The patent changes the physical and chemical parameters of the formulation by using enteric-coated microtablets with specific pH-dependent solubility characteristics, maintaining dimethyl fumarate in a stable solid state at low pH in the stomach while allowing dissolution and absorption in the higher pH environment of the intestine
2Stability of the object's composition
If stabilizing agents are added to prevent photodegradation, then stability of dimethyl fumarate is improved, but complexity of the pharmaceutical composition increases
Solution Approach 1:
The patent applies local quality by providing different protective characteristics to different parts of the gastrointestinal tract through enteric coating, protecting dimethyl fumarate from acidic degradation in the stomach while allowing controlled release in the intestine, without adding systemic stabilizing agents throughout the entire formulation
3Stability of the object's composition
If enteric coating is applied to prevent degradation, then stability during gastric transit is improved, but manufacturing precision requirements increase
Solution Approach 1:
The patent applies preliminary action by pre-coating the dimethyl fumarate microtablets with enteric material before final formulation and packaging, ensuring protective coverage is established prior to distribution and handling, which maintains stability throughout the supply chain without requiring complex real-time monitoring
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 maintain the stability and therapeutic potency of dimethyl fumarate, reducing the formation of undesirable compounds and enhancing the efficacy of treatments for multiple sclerosis and psoriasis.
Implementation Method 1
Dimethyl fumarate is susceptible to photodegradation and oxidation, leading to the formation of undesirable impurities
Implementation Method 2
Dimethyl fumarate is susceptible to photodegradation and oxidation, leading to the formation of undesirable impurities
Data Source
AI summary
Pharmaceutical compositions and dosage forms of dimethyl fumarate containing low levels of certain impurities are disclosed.