Ibrutinib Solid State Forms G J K Crystallization
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Solution Overview
Problem
There is a need for additional solid state forms of Ibrutinib to improve its processing properties, stability, and bioavailability, as existing forms may have limitations in handling, purification, and shelf-life.
Innovation Solution
Development of novel solid state forms of Ibrutinib, including crystalline forms G, J, and K, characterized by specific X-ray powder diffraction patterns and thermal properties, which can be used to create pharmaceutical compositions with improved chemical purity, solubility, and stability, and prepared through controlled crystallization processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If existing solid state forms of Ibrutinib are used, then the basic therapeutic function is achieved, but processing properties and handling characteristics are limited
Solution Approach 1:
The patent applies parameter changes by discovering and utilizing different polymorphic forms (Forms A through K) of Ibrutinib, each with distinct crystal structures and physical properties. By changing the solid state form parameter, the patent improves processing properties such as crystallinity, dissolution rate, and compressibility while maintaining the therapeutic function, thereby resolving the contradiction between ease of manufacture and ease of operation.
Solution Approach 2:
The patent employs phase transitions by converting Ibrutinib between different solid state forms (polymorphs) and amorphous states through controlled crystallization processes. This allows optimization of handling characteristics and processing properties by selecting the appropriate phase form for specific manufacturing operations, resolving the technical contradiction between manufacturability and operational ease.
2Reliability
If existing solid state forms of Ibrutinib are used, then the drug can be formulated, but stability and shelf-life are insufficient
Solution Approach 1:
The patent resolves the contradiction between stability and shelf-life by changing the solid state form parameter of Ibrutinib. Different polymorphic forms exhibit varying degrees of chemical and physical stability, with some forms demonstrating superior resistance to degradation and polymorphic conversion over time. By selecting appropriate stable forms, the patent extends shelf-life while maintaining reliability.
3Productivity
If existing solid state forms of Ibrutinib are used, then basic formulation is possible, but dissolution profile and bioavailability are suboptimal
Solution Approach 1:
The patent addresses the contradiction between dissolution profile and bioavailability by changing the solid state form parameter. Different polymorphic forms of Ibrutinib exhibit distinct dissolution rates and solubility characteristics. By selecting forms with optimized dissolution profiles, the patent improves both productivity (faster dissolution) and manufacturing precision (consistent bioavailability), resolving the technical contradiction.
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 solid state forms of Ibrutinib offer enhanced chemical purity, stability, and handling characteristics, such as improved solubility and storage stability, making them suitable for pharmaceutical applications and cancer treatment.
Implementation Method 1
prepared through controlled crystallization processes
Data Source
AI summary
The present invention encompasses solid state forms of Ibrutinib, including forms G, J and K, and pharmaceutical compositions thereof.