Crystalline Form A for Stable Processing of Compound (I)
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Solution Overview
Problem
Existing methods for isolating and purifying 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (Compound (I)) for pharmaceutical use lack a stable solid form that can be reproducibly produced and processed into other forms, such as amorphous forms, with sufficient solvent solubility.
Innovation Solution
Development of a crystalline form, designated as Form A, which is physically and chemically stable at various storage conditions, allowing for conversion into other solid forms and has sufficient solubility in solvents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional isolation and purification methods are used for Compound (I), then the compound can be obtained as a purified solid, but the solid form lacks physical and chemical stability at various storage conditions and cannot be reproducibly produced
Solution Approach 1:
The patent applies parameter changes by identifying and controlling specific crystallization parameters (temperature, solvent composition, pH, addition rate) to transform the compound from an unstable purified solid into a stable crystalline form. The method systematically adjusts these parameters to achieve reproducible formation of crystalline Form A with defined stability characteristics.
Solution Approach 2:
The invention utilizes phase transitions by inducing controlled crystallization of Compound (I) from solution to solid state. This phase transition from dissolved compound to ordered crystal structure is achieved through controlled cooling, solvent evaporation, or addition of anti-solvent, resulting in a stable solid form with predictable physical and chemical properties.
2Ease of manufacture
If the compound is isolated as a purified solid, then it can be separated from reaction mixture, but it lacks sufficient solubility in solvents for preparation of other solid forms
Solution Approach 1:
The patent employs parameter changes to optimize solubility by adjusting solvent type, temperature, and pH conditions. The crystallization method identifies solvent systems where the compound exhibits appropriate solubility characteristics, enabling subsequent processing into amorphous forms or other solid dosage forms while maintaining stability.
3Reliability
If multiple isolation and purification steps are performed to obtain purified compound, then impurities are removed, but the compound is obtained in forms that are not amenable to additional processing
Solution Approach 1:
The invention uses controlled phase transition to crystallization to produce a solid form that maintains chemical stability while being amenable to further processing. The crystalline structure obtained through controlled crystallization can be subsequently converted to amorphous forms or other solid forms as needed for pharmaceutical formulations.
Solution Approach 2:
The method applies parameter changes to achieve a solid form with optimal balance between stability and processability. By controlling crystallization parameters, the compound is obtained in a stable crystalline form that can be converted to other forms (such as amorphous forms) when required for specific pharmaceutical applications.
Data Source
AI summary
Disclosed is crystalline Form A of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl) amino)-N-(methyl-d3)pyridazine-3-carboxamide. Form A is a neat crystalline form. Characterization data for Form A are disclosed.