Thiazolidinone Salt Polymorphs for MS Drug Stability
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Solution Overview
Problem
There is a need for novel drug products to treat multiple sclerosis and other autoimmune diseases affecting the central nervous system, as existing technologies face challenges in predicting and preparing stable crystalline forms of pharmaceutical compounds, which affect solubility, stability, and bioavailability.
Innovation Solution
Development of salts and solid forms of (Z)-5-((Z)-3-chloro-4-((R)-2,3-dihydroxypropoxy)benzylidene)-2-(propylimino)-3-(o-tolyl)thiazolidin-4-one, including HCl, HBr, napadisylate, and other acid salts, in crystalline and amorphous forms, to enhance pharmaceutical properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If crystalline forms of pharmaceutical compounds are prepared, then physical and chemical stability is improved, but prediction and preparation of stable crystalline forms becomes complex and unpredictable
Solution Approach 1:
The patent applies parameter changes by systematically varying crystallization conditions including solvent type, temperature, pH, and concentration to discover and characterize multiple stable crystalline forms (polymorphs) of ponesimod. This approach transforms the unpredictable process into a systematic exploration of parameter space, enabling rational design of stable solid forms with desired properties.
Solution Approach 2:
The patent utilizes phase transitions by inducing and characterizing different crystalline phases (polymorphs) of the pharmaceutical compound through controlled crystallization processes. By understanding and controlling these phase transitions, the patent identifies stable crystalline forms that provide improved physical and chemical stability for the drug product.
2Adaptability or versatility
If alternative solid forms are developed, then pharmaceutical properties such as solubility and bioavailability can be modulated, but the selection process becomes complex due to multiple affecting properties
Solution Approach 1:
The patent systematically explores different solid forms including crystalline polymorphs, solvates, and amorphous forms by varying preparation parameters such as solvent selection, crystallization temperature, and drying conditions. This comprehensive parameter exploration enables identification of solid forms with optimized solubility, stability, and bioavailability characteristics.
Solution Approach 2:
The patent creates multiple copies of the pharmaceutical compound in different solid forms (polymorphs, solvates, amorphous) to evaluate their respective properties. By preparing and characterizing these alternative forms, the patent enables selection of the most suitable solid form for specific pharmaceutical applications based on desired properties.
3Ease of operation
If salts of the compound are prepared, then solubility and bioavailability are enhanced, but the number of possible salt forms increases complexity
Solution Approach 1:
The patent prepares and characterizes multiple salt forms of ponesimod by reacting the compound with different acids (e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid) and varying reaction conditions. This systematic approach identifies salt forms with improved solubility and bioavailability while managing the complexity through structured exploration.
Data Source
AI summary
Provided herein are formulations, processes, solid forms and methods of use relating to salts of (Z)-5-((Z)-3-chloro-4-((R)-2,3-dihydroxypropoxy)benzylidene)-2-(propylimino)-3-(o-tolyl)thiazolidin-4-one.