PARP14 Inhibitor Solid Forms for Storage Stability
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Solution Overview
Problem
There is a need for new solid forms of PARP14-inhibiting molecules with suitable properties for preparing pharmaceutically useful formulations to facilitate the manufacture of safe and effective drug products for treating cancer and inflammatory diseases.
Innovation Solution
The development of solid forms, including crystalline forms, of 7-((1-acetylpiperidin-4-yl)methoxy)-5-fluoro-2-(((tetrahydro-2H-pyran-4-yl)thio)methyl)quinazolin-4(3H)-one, which can be used in pharmaceutical compositions and therapeutic methods to inhibit PARP14 activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If new solid forms of PARP14 inhibitor are developed, then storage stability and bioavailability are improved, but the complexity of formulation development increases
Solution Approach 1:
The patent applies parameter changes by developing multiple crystalline forms (polymorphs, solvates, hydrates) of the PARP14 inhibitor with different physical and chemical parameters. Each crystalline form has distinct properties such as solubility, melting point, and stability, allowing optimization of formulation characteristics without changing the chemical structure of the active ingredient.
Solution Approach 2:
The patent utilizes phase transitions by creating different solid-state forms of the inhibitor including amorphous, crystalline, polymorphic, and solvated forms. These phase transitions enable the development of formulations with improved storage stability and bioavailability while providing options for different manufacturing and delivery requirements.
2Ease of operation
If multiple crystalline forms are developed, then ease of handling and processing are improved, but the manufacturing process complexity increases
Solution Approach 1:
The patent changes physical parameters of the inhibitor by developing crystalline forms with different properties such as particle size, morphology, and crystal structure. These parameter changes improve ease of handling, flow properties, and processing characteristics while allowing selection of optimal forms for specific manufacturing processes.
Solution Approach 2:
The patent provides multiple crystalline forms that can be selected based on specific manufacturing needs, allowing the use of the most suitable form for each process step. This approach enables optimization of each manufacturing stage without requiring complex multi-step processes for a single form.
3Reliability
If solid forms with improved bioavailability are created, then therapeutic effectiveness is enhanced, but the characterization and quality control difficulty increases
Solution Approach 1:
The patent changes the physical state and crystalline structure parameters of the inhibitor to improve bioavailability. Different crystalline forms exhibit different dissolution rates and solubility characteristics, which directly impact bioavailability. The patent provides characterization data for each form to facilitate quality control despite the increased complexity.
Data Source
AI summary
The present invention relates to solid forms of the poly(ADP-ribose) polymerase 14 (PARP14) inhibitor 7-((1-acetylpiperidin-4-yl)methoxy)-5-fluoro-2-(((tetrahydro-2H-pyran-4-yl)thio)methyl)quinazolin-4(3H)-one, including methods of preparation thereof, where the inhibitor is useful in the treatment of cancer and inflammatory diseases.