PKC Inhibitor Solid Forms for Stability and Bioavailability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing treatments for cancer, immune disorders, and inflammation lack effective protein kinase inhibitor compounds in stable and efficient solid state 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 and hydrates, to enhance therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional protein kinase inhibitor compounds are used, then cancer, immune disorders, and inflammation can be treated, but the solid state forms lack stability and bioavailability
Solution Approach 1:
The patent applies parameter changes by creating multiple solid state forms (crystalline forms I-VI, amorphous forms, hydrates, solvates) of the protein kinase inhibitor compound. Each form represents a different physical state or crystalline structure with distinct properties. This allows optimization of stability, bioavailability, and manufacturing characteristics by selecting or developing the appropriate solid state form for specific therapeutic applications.
Solution Approach 2:
The patent creates composite solid state forms including hydrates (containing water molecules) and solvates (containing solvent molecules) of the compound. These composite forms combine the inhibitor compound with other substances in specific stoichiometric ratios to achieve improved stability and bioavailability while maintaining the therapeutic activity of the parent compound.
2Reliability
If conventional protein kinase inhibitor compounds are used, then cancer, immune disorders, and inflammation can be treated, but bioavailability is insufficient
Solution Approach 1:
The patent optimizes bioavailability by developing specific solid state forms with controlled crystalline structures and physical properties. Different crystalline forms (I-VI) and amorphous forms provide varied dissolution rates and absorption characteristics, allowing enhancement of bioavailability while maintaining therapeutic efficacy through careful selection and formulation of the appropriate solid state form.
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 improved stability and bioavailability, enabling effective treatment of cancer, immune disorders, and inflammation.
Implementation Method 1
crystalline 2-propanol solvate Form A 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 is 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.