PKC Inhibitor Crystalline Forms for Stability and Bioavailability
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Solution Overview
Problem
Current treatments for cancer, immune disorders, and inflammation lack effective protein kinase inhibitor compounds in stable and bioavailable forms.
Innovation Solution
Development of various solid state forms of 5-{[(2S,5R)-2,5-dimethyl-4-(tetrahydro-2H-pyran-4-ylmethyl)piperazin-1-yl]carbonyl}-N-(5-fluoro-2-methylpyrimidin-4-yl)-6,6-dimethyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-amine, including amorphous and crystalline forms with specific X-ray diffraction patterns, to enhance stability and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If protein kinase inhibitor compounds are developed for treating cancer, immune disorders, and inflammation, then therapeutic effectiveness is improved, but stability and bioavailability of the compounds are insufficient
Solution Approach 1:
The patent applies parameter changes by transforming the compound from liquid or unstable solid forms into stable solid state forms (amorphous and crystalline forms). This changes the physical state parameters of the compound, thereby improving stability and bioavailability while maintaining therapeutic effectiveness. The solid state forms exhibit enhanced pharmacokinetic properties compared to the liquid form.
Solution Approach 2:
The patent creates composite material structures by forming crystalline lattices and solvates with specific solvents. These composite structures provide both stability and controlled release properties, resolving the contradiction between therapeutic effectiveness and stability/bioavailability.
2Stability of the object's composition
If solid state forms of the compound are developed, then stability is improved, but identification and characterization of the forms becomes more complex
Solution Approach 1:
The patent uses X-ray diffraction patterns as characteristic 'fingerprints' for identifying different solid state forms. Each crystalline form produces a unique diffraction pattern that serves as a reliable identification method, simplifying the detection and characterization process despite the complexity of multiple solid forms.
Solution Approach 2:
The patent establishes a feedback system where X-ray diffraction data and other analytical data are used to characterize and identify solid state forms. This systematic approach provides clear criteria for differentiation and quality control, making the characterization process more manageable.
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
The solid state forms provide enhanced stability and bioavailability, making them effective for treating cancer, immune disorders, and inflammation.
Implementation Method 1
characterized by an X-ray diffraction pattern reflection at a 2 theta value of 18.1
Data Source
AI summary
The present disclosure relates to various solid state forms of 5-{[(2S,5R)-2,5-dimethyl-4-(tetrahydro-2H-pyran-4-ylmethyl)piperazin-1-yl]carbonyl}-N-(5-fluoro-2-methylpyrimidin-4-yl)-6,6-dimethyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-amine and methods of making the same. Such forms of 5-{[(2S,5R)-2,5-dimethyl-4-(tetrahydro-2H-pyran-4-ylmethyl)piperazin-1-yl]carbonyl}-N-(5-fluoro-2-methylpyrimidin-4-yl)-6,6-dimethyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-amine are useful in preparation of pharmaceutical compositions and dosage forms for the treatment of cancer, immune disorders and inflammation.