Anhydrous Relugolix Form T Crystallization Process
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Solution Overview
Problem
Current methods for producing anhydrous relugolix forms, such as Form T, face challenges in achieving stable and efficient conversion from existing solid-state forms like Form A DMF solvate or amorphous relugolix, requiring effective processes to isolate and characterize these forms for pharmaceutical applications.
Innovation Solution
The process involves converting Form A DMF solvate or amorphous relugolix into Form T anhydrous relugolix through methods like mixing with an alcohol at elevated temperatures, followed by cooling and filtration, or mixing with an alcohol to form a slurry, utilizing techniques like XRPD, DSC, TGA, and NMR for characterization and purification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If recrystallization methods using alkyl alcohol and solvents like DMF, DMSO, or DMA are used to produce anhydrous relugolix, then the conversion from solvate forms can be achieved, but the process stability and consistency for pharmaceutical applications are insufficient
Solution Approach 1:
The patent applies parameter changes by systematically varying crystallization conditions including temperature profiles, solvent ratios, pH levels, and mixing rates to optimize the conversion from solvate forms to anhydrous relugolix. These parameter optimizations ensure consistent and reliable production of Form T anhydrous relugolix with high purity and reproducible crystal structure.
Solution Approach 2:
The patent utilizes phase transitions during the crystallization process, controlling the transformation from solvate phases to anhydrous crystalline form through temperature-controlled cooling and evaporation. This phase transition approach enables consistent formation of Form T anhydrous relugolix with defined crystal structure and high purity.
2Ease of manufacture
If existing crystalline forms like Form A DMF solvate or Form B anhydrous relugolix are used as starting materials, then the production process can be initiated, but achieving stable conversion to Form T requires complex purification and characterization
Solution Approach 1:
The patent employs intermediary substances and conditions during the conversion process, using controlled solvent systems and intermediate crystallization steps to facilitate the transformation from starting materials to Form T anhydrous relugolix. This intermediary approach simplifies the overall process by breaking down the conversion into manageable stages with defined purification points.
Solution Approach 2:
The patent replaces complex mechanical purification systems with optimized chemical and physical processes, using controlled crystallization and filtration methods that are easier to implement and scale. This substitution reduces device complexity while maintaining high purity standards for the final anhydrous relugolix product.
3Manufacturing precision
If high purity and consistency are required for pharmaceutical applications, then Form T anhydrous relugolix can be produced, but the process requires precise control and characterization techniques
Solution Approach 1:
The patent implements feedback mechanisms through in-process monitoring and characterization techniques, using XRPD, DSC, and other analytical methods to verify crystal form and purity at various stages. This feedback allows for real-time process adjustment to maintain high manufacturing precision and ensure consistent production of Form T anhydrous relugolix meeting pharmaceutical standards.
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 method allows for the stable production and characterization of Form T anhydrous relugolix, ensuring high purity and consistency, which is crucial for pharmaceutical applications, particularly for treating uterine fibroids and potentially endometriosis-associated pain and prostate cancer.
Implementation Method 1
mixing with an alcohol at elevated temperatures, followed by cooling and filtration
Implementation Method 2
converting Form A DMF solvate or amorphous relugolix into Form T anhydrous relugolix through methods like mixing with an alcohol at elevated temperatures, followed by cooling and filtration
Implementation Method 3
converting Form A DMF solvate or amorphous relugolix into Form T anhydrous relugolix
Data Source
AI summary
The present invention is directed to processes for making an anhydrous form of relugolix, designated herein as Form T of anhydrous relugolix. The processes of making Form T of anhydrous relugolix are from the following: (i) Form A of the DMF solvate of relugolix; (ii) Form B of anhydrous relugolix; or (iii) amorphous relugolix.