Tetrahydropyranyl BTK Inhibitor Solid Forms for Stability and Solubility
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Solution Overview
Problem
There is a need for potent small molecule inhibitors of Bruton's tyrosine kinase (BTK) to treat immune disorders, cancer, cardiovascular disease, viral infections, inflammation, metabolism/endocrine function disorders, and neurological disorders, as existing treatments are inadequate.
Innovation Solution
Development of solid forms, including amorphous and crystalline forms, of the BTK inhibitor (2-chloro-4-phenoxyphenyl)(4-(((3R,6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)methanone, characterized by specific XRPD patterns and thermal events, to enhance therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If small molecule BTK inhibitors are developed to treat immune disorders and cancers, then therapeutic efficacy is improved, but drug stability and solubility may be compromised
Solution Approach 1:
The patent applies parameter changes by developing multiple solid forms (amorphous and crystalline polymorphs) of the BTK inhibitor compound. Each solid form has distinct physical parameters including different melting points, solubilities, and stabilities. The amorphous form provides enhanced solubility while crystalline forms offer improved stability, allowing optimization of therapeutic efficacy without compromising drug stability.
Solution Approach 2:
The patent employs composite materials by creating pharmaceutical compositions that combine the BTK inhibitor with specific excipients and carriers. These compositions are formulated to maintain the therapeutic efficacy of the active compound while providing the stability and solubility characteristics needed for clinical use. The composite formulation approach allows simultaneous achievement of multiple desired properties.
2Reliability
If small molecule BTK inhibitors are developed to treat immune disorders and cancers, then therapeutic efficacy is improved, but solubility may be compromised
Solution Approach 1:
The patent utilizes parameter changes by establishing different solid forms with varying solubility parameters. The amorphous solid form specifically provides enhanced solubility compared to crystalline forms, while maintaining the same therapeutic active compound. This allows the drug to achieve both high therapeutic efficacy and adequate solubility for bioavailability.
Data Source
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AI summary
The present application provides solid forms of (2-chloro-4-phenoxyphenyl)(4-(((3R,6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)methanone free base, and methods of preparing and using the same.