Pyrazole Crystal Form I Polymorph Control
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Solution Overview
Problem
The existing methods for preparing 4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide do not adequately address the isolation and characterization of its crystal forms, leading to issues with polymorphic behavior, tablet stability, and chemical production problems such as filterability and analytical reproducibility.
Innovation Solution
The development of a crystal form (Form I) with specific powder X-ray diffraction patterns and a process for converting Form II to Form I involving solvent mixtures like water, methanol, and ethanol, along with temperature and stirring conditions, to achieve stable and reproducible crystal formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing preparation methods are used without specific crystal form control, then the compound can be synthesized, but polymorphic behavior causes tablet stability problems and analytical reproducibility issues
Solution Approach 1:
The patent applies parameter changes by controlling crystallization conditions including temperature ranges (0-60°C), solvent composition ratios, pH levels, and agitation rates to obtain a specific crystal form (Form I) with defined X-ray diffraction patterns, thereby eliminating polymorphic behavior and ensuring tablet stability and analytical reproducibility
Solution Approach 2:
The patent utilizes phase transitions by controlling the crystallization process from solution to solid phase under specific conditions (temperature, solvent composition, pH) to obtain a stable crystal form (Form I) with characteristic X-ray diffraction patterns, preventing polymorphic transitions that would compromise tablet stability
2Ease of manufacture
If existing preparation methods are used without specific crystal form control, then the compound can be synthesized, but filterability problems occur during chemical production
Solution Approach 1:
The patent applies parameter changes by optimizing crystallization conditions including temperature (0-60°C), solvent composition, pH, and agitation to produce crystals with controlled size distribution and morphology (Form I), which exhibit improved filterability while maintaining chemical production efficiency
3Measurement precision
If existing preparation methods are used without specific crystal form control, then the compound can be synthesized, but analytical reproducibility is compromised
Solution Approach 1:
The patent applies parameter changes by precisely controlling crystallization parameters including temperature (0-60°C), solvent composition ratios, pH levels, and agitation rates to obtain a reproducible crystal form (Form I) with characteristic X-ray diffraction patterns, ensuring analytical reproducibility across different batches
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
This approach ensures the production of a stable crystal form (Form I) with improved tablet stability and analytical reproducibility, addressing the challenges of polymorphic behavior and chemical production issues.
Implementation Method 1
having a powder X-ray diffraction pattern comprising peaks expressed in degrees (±0.1 degree) of two theta angle of 14.0, 18.9, 21.3, 21.9, and 25.7 obtained using CuKα1 X-ray
Implementation Method 2
powder X-ray diffraction pattern comprising peaks expressed in degrees (±0.1 degree) of two theta angle
Implementation Method 3
stirring the suspension at a temperature from about 0° C. to about 60° C. for 24 to 72 hours; collecting the Form I crystals
Implementation Method 4
precipitating the compound by the addition of water; stirring the suspension of step (ii) for 2 to 72 hours
Data Source
AI summary
The present invention relates to crystal forms of 4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide and methods for preparation, interconversion, and isolation of such crystals.