BET Inhibitor Crystal Forms for Stable Bioavailable Formulations
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Solution Overview
Problem
Current pharmaceutical formulations of bromodomain-containing protein inhibitors lack stable and well-defined crystal forms, which can affect their efficacy and stability, particularly in the treatment of diseases such as cancer, inflammation, and autoimmune diseases.
Innovation Solution
Development of specific crystal forms and pharmaceutically acceptable salts of bromodomain-containing protein inhibitors, characterized by distinct X-ray powder diffraction peaks and preparation methods using solvents like water, acetonitrile, methanol, and dimethyl sulfoxide, to enhance stability and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional pharmaceutical formulations of bromodomain-containing protein inhibitors are used, then the basic therapeutic effect can be achieved, but the stability and bioavailability are insufficient
Solution Approach 1:
The patent applies parameter changes by establishing specific crystal forms (Form I, Form II, Form III) with defined X-ray diffraction patterns and controlling polymorphic transformations. By precisely controlling crystallization parameters such as temperature, solvent composition, and cooling rates, the patent achieves enhanced stability and defined physical properties for the bromodomain-containing protein inhibitor formulations.
Solution Approach 2:
The patent utilizes phase transitions in the crystallization process to obtain stable crystal forms. By controlling the phase transition from amorphous to crystalline state through specific cooling and solvent removal processes, the patent achieves formulations with improved stability and defined physical characteristics, while managing the complexity through standardized crystallization protocols.
2Reliability
If conventional pharmaceutical formulations are used, then the basic therapeutic effect can be achieved, but the bioavailability is insufficient
Solution Approach 1:
The patent applies parameter changes by optimizing crystal structure parameters and polymorphic forms to enhance bioavailability. By controlling the crystal form (Form I, II, or III) and their specific physical properties such as lattice energy and surface area, the patent improves drug absorption and bioavailability while maintaining formulation processes within acceptable complexity ranges.
Solution Approach 2:
The patent utilizes phase transitions during crystallization to create formulations with improved bioavailability. By controlling the phase transition process and obtaining specific crystal forms with optimized physical properties, the patent enhances drug dissolution and absorption characteristics without requiring overly complex formulation procedures.
3Reliability
If stable crystal forms are developed through extensive characterization, then the reliability and bioavailability are improved, but the development time and complexity increase
Solution Approach 1:
The patent applies preliminary action by pre-establishing the crystallization protocols and characterization methods before actual formulation development. By preparing the crystallization conditions, solvent systems, and analysis methods in advance, the patent reduces the overall development time while still achieving thorough characterization of the crystal forms and their therapeutic properties.
Solution Approach 2:
The patent applies parameter changes by optimizing the balance between characterization thoroughness and development time. By identifying the critical parameters that define crystal form stability and bioavailability, the patent achieves reliable therapeutic efficacy data without requiring exhaustive characterization of all possible crystal forms, thus reducing development time.
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 developed crystal forms and salts provide improved stability, bioavailability, and therapeutic efficacy, making them suitable for treating conditions like cancer, inflammation, and autoimmune diseases.
Implementation Method 1
characterized by distinct X-ray powder diffraction peaks
Implementation Method 2
characterized diffraction peaks at the following 2θ: 12.4°±0.2°, 14.5°±0.2°, 17.4°±0.2°, 18.5°±0.2°, 20.4°±0.2°, and 24.7°±0.2° in an X-ray powder diffraction pattern
Data Source
AI summary
A crystal form and salt form of a bromine domain protein inhibitor represented by formula (I), a preparation method therefor, and a use of the crystal form and salt form in the preparation of a drug for treating diseases mediated by BET protein.