Acalabrutinib Polymorphs for Solubility and Stability Control
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Solution Overview
Problem
Existing Acalabrutinib polymorphs do not adequately address differences in dissolution characteristics, bioavailability, solubility, handling properties, and stability, which are crucial for pharmaceutical performance.
Innovation Solution
Development of new polymorphic forms, namely Form-C2, Form-C3, Form-C4, and Form-C5, characterized by distinct X-ray diffraction patterns, DSC, and TGA profiles, prepared through specific solvent and temperature-controlled processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing Acalabrutinib polymorphs are used, then the drug can be manufactured and administered, but the dissolution characteristics, bioavailability, solubility, handling properties, and stability are not adequately optimized
Solution Approach 1:
The patent applies parameter changes by discovering and characterizing five new polymorphic forms (Form-C2 through Form-C5) of Acalabrutinib, each with distinct crystal structures and physical properties. These polymorphs exhibit different dissolution rates, solubilities, and stability profiles, allowing optimization of pharmaceutical performance through selection of the appropriate polymorphic form for specific therapeutic applications
Solution Approach 2:
The invention utilizes phase transitions by establishing controlled crystallization processes that transform Acalabrutinib from amorphous or less stable crystalline states into specific, stable polymorphic forms. The patent describes methods involving solvent selection, temperature control, and crystallization conditions to induce formation of desired polymorphs with enhanced pharmaceutical properties
2Stability of the object's composition
If new polymorphic forms are developed through specific solvent and temperature-controlled processes, then solubility and stability are enhanced, but the manufacturing process complexity increases
Solution Approach 1:
The patent resolves this contradiction by identifying specific parameter ranges for solvent type, temperature, and crystallization conditions that reliably produce stable polymorphic forms. By establishing defined parameter windows, the process achieves both enhanced stability and manufacturability without excessive complexity
Solution Approach 2:
The invention uses solvent molecules as intermediaries during the crystallization process to facilitate formation of specific polymorphic forms. The selected solvents mediate the crystallization process by interacting with Acalabrutinib molecules in specific ways that promote desired crystal packing arrangements, thereby achieving stable polymorphs through controlled intermediary interactions
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 new polymorphic forms exhibit improved pharmaceutical properties, including enhanced solubility and stability, facilitating better drug performance and treatment efficacy, particularly in treating mantle cell lymphoma (MCL).
Implementation Method 1
characterized by XRD, DSC, IR and TGA
Implementation Method 2
distinct X-ray diffractogram
Implementation Method 3
differential scanning calorimetry (DSC)
Implementation Method 4
thermogravimetric analysis (TGA)
Data Source
AI summary
The present invention discloses novel crystalline polymorphic forms of Acalabrutinib, methods of preparation, pharmaceutical compositions and methods of therapeutic treatment involving polymorphic forms thereof.