BTK Inhibitor Crystalline Forms for Stability and Solubility
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Solution Overview
Problem
Current treatments for diseases associated with Bruton's tyrosine kinase (Btk) activity lack effective and stable formulations of Btk inhibitors, which are crucial for therapeutic efficacy.
Innovation Solution
Development of crystalline forms and pharmaceutically acceptable salts of the Btk inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, including polymorphs, solvates, and amorphous phases, to enhance stability and therapeutic effectiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If crystalline forms of Btk inhibitor are developed, then stability and therapeutic efficacy are improved, but formulation complexity increases
Solution Approach 1:
The patent applies parameter changes by developing multiple crystalline forms (polymorphs) of the Btk inhibitor with different physical and chemical parameters. Each polymorph exhibits distinct stability characteristics, solubility profiles, and melting points, allowing selection of the most appropriate form for specific therapeutic applications while maintaining improved reliability over non-crystalline forms
Solution Approach 2:
The patent utilizes phase transitions by characterizing and utilizing different solid-state phases (polymorphs) of the Btk inhibitor. The transition between different crystalline forms and their relationship to solubility and stability enables optimized formulation development, where specific phase transitions can be controlled to achieve desired therapeutic outcomes
2Quantity of substance
If crystalline forms of Btk inhibitor are developed, then solubility is improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies parameter changes by developing multiple crystalline forms (polymorphs) of the Btk inhibitor with different physical and chemical parameters. Each polymorph exhibits distinct stability characteristics, solubility profiles, and melting points, allowing selection of the most appropriate form for specific therapeutic applications while maintaining improved reliability over non-crystalline forms
Solution Approach 2:
The patent employs solvates as intermediary structures where solvent molecules are incorporated into the crystal lattice of the Btk inhibitor. These solvates serve as mediators between the hydrophobic inhibitor molecule and the aqueous biological environment, enhancing solubility while providing a defined crystalline structure that facilitates manufacturing through controlled crystallization processes
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 crystalline forms provide improved stability, solubility, and therapeutic efficacy, enabling effective treatment of diseases mediated by Btk activity.
Implementation Method 1
Development of crystalline forms and pharmaceutically acceptable salts of the Btk inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, including polymorphs, solvates, and amorphous phases
Data Source
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AI summary
Described herein is the Bruton's tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, including crystalline forms, solvates and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions that include the Btk inhibitor, as well as methods of using the Btk inhibitor, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.