PARP7 Inhibitor Solid Forms for Stable, Bioavailable Formulations
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Solution Overview
Problem
There is a need for new solid forms of PARP7-inhibiting molecules to develop pharmaceutically useful formulations that facilitate the manufacture of safe, effective, and high-quality drug products, particularly to address the mechanism by which cancer cells evade the host immune system through suppression of Type I interferons and T cell-mediated antitumor immunity.
Innovation Solution
The development of solid forms of 5-[[(2S)-1-(3-oxo-3-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propoxy)propan-2-yl]amino]-4-(trifluoromethyl)-2,3-dihydropyridazin-3-one and its salts, including crystalline forms and benzenesulfonic acid salts, which are suitable for pharmaceutical compositions and therapeutic applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If new solid forms of PARP7 inhibitor are developed, then storage stability and ease of handling are improved, but formulation complexity increases
Solution Approach 1:
The patent applies parameter changes by developing multiple crystalline forms (polymorphs) of the PARP7 inhibitor with different physical and chemical parameters. Each crystalline form has distinct properties such as melting point, solubility, and stability, allowing selection of the optimal form for specific pharmaceutical applications while maintaining storage stability and handling ease.
Solution Approach 2:
The patent employs composite materials by creating co-crystals and solvates of the PARP7 inhibitor with various co-formers. These composite structures combine the inhibitor with other molecules in defined stoichiometric ratios, resulting in new solid forms with improved stability and handling properties while managing formulation complexity through systematic design.
2Productivity
If crystalline forms are developed, then dissolution profile and bioavailability are improved, but manufacturing process complexity increases
Solution Approach 1:
The patent applies preliminary action by pre-characterizing multiple crystalline forms and their dissolution profiles during the development phase. This allows the selection of the most suitable crystalline form for high bioavailability before scale-up, avoiding manufacturing complexities that would arise from optimizing crystallization conditions at later stages.
Solution Approach 2:
The patent employs this principle by developing crystalline forms that can be manufactured using simple, cost-effective methods such as solvent evaporation or grinding, rather than requiring complex multi-step synthesis procedures. This reduces manufacturing process complexity while maintaining high bioavailability through improved dissolution properties.
3Adaptability or versatility
If multiple solid forms are created, then pharmaceutical formulation options are expanded, but characterization and quality control difficulty increases
Solution Approach 1:
The patent applies segmentation by systematically categorizing and characterizing each solid form (polymorph, co-crystal, solvate) with distinct identification markers such as specific XRD patterns, DSC transitions, and solubility profiles. This segmented approach allows for expanded formulation options while simplifying quality control through form-specific characterization protocols.
Data Source
AI summary
The present invention relates to solid forms of the poly(ADP-ribose) polymerase 7 (PARP7) inhibitor 5-[[(2S)-1-(3-oxo-3-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propoxy)propan-2-yl]amino]-4-(trifluoromethyl)-2,3-dihydropyridazin-3-one, and salts thereof, including methods of preparation thereof, where the inhibitor is useful in the treatment of cancer.