Vidofludimus Calcium Polymorph A for DHODH Inhibition
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Solution Overview
Problem
Current treatments for inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease, which target dihydroorotate dehydrogenase (DHODH), face limitations in efficacy and the need for new medications due to the aging population and existing treatment unsatisfactoriness.
Innovation Solution
Development of a white crystalline polymorph A of the calcium salt of vidofludimus, characterized by specific X-ray powder diffraction peaks, which effectively inhibits DHODH and is formulated to have a Tetrahydrofuran (THF) content below 720 ppm for compliance with regulatory guidelines.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing DHODH inhibitor medications are used for treatment, then anti-inflammatory activity is achieved, but treatment efficacy is insufficient and new medications are needed due to aging population
Solution Approach 1:
The patent develops new calcium salt polymorphs of DHODH inhibitors with specific crystalline structures (polymorph A and B) that exhibit improved anti-inflammatory activity and pharmacological properties. By changing the physical and chemical parameters of the compound (polymorphic form, salt type), the invention achieves enhanced treatment efficacy while maintaining suitability for diverse patient populations including the aging demographic
2Reliability
If calcium salt polymorphs are developed for improved efficacy, then anti-inflammatory activity increases, but manufacturing complexity and characterization requirements increase
Solution Approach 1:
The patent employs X-ray powder diffraction (XRPD) technology to characterize and differentiate the calcium salt polymorphs. This analytical method replaces complex manual characterization procedures with a standardized, objective technique that provides clear diagnostic patterns for identifying polymorph A and B, thereby managing the complexity of polymorph characterization while ensuring improved anti-inflammatory activity
3Object-affected harmful factors
If THF content is reduced to meet regulatory guidelines, then compliance with EMA guidelines is achieved, but process optimization and solvent removal complexity increase
Solution Approach 1:
The patent develops specific crystallization and purification processes that control the solvent content in the final polymorph product. By optimizing crystallization conditions and employing controlled solvent removal techniques, the invention achieves THF content below 720 ppm (compliance with EMA guidelines) while maintaining the stability and properties of the calcium salt polymorphs
Data Source
AI summary
Subject matter of the present invention is a white crystalline polymorph A of the Ca salt of a compound according to formula I or a solvate and/or a hydrate thereof with a molar ratio of a compound according to formula I or a solvate and/or a hydrate thereof to calcium which is 2±0.3. Subject matter of the present invention is in particular a compound according to formula I or a solvate and/or a hydrate thereof which is characterized by an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2theta at ±0.2 of the values shown below: 2 theta=5.91°, 9.64°, 16.78°, 17.81°, 19.81°, 25.41° In particular the invention refers to new polymorphs of calcium salts of the Ca salt of a compound according to formula I or a solvate and/or a hydrate thereof which inhibits dihydroorotate dehydrogenase (DHODH), a process for their manufacture, pharmaceutical compositions containing them and to their use for the treatment and prevention of diseases, in particular their use in diseases where there is an advantage in inhibiting dihydroorotate dehydrogenase (DHODH).