Bardoxolone Methyl Crystalline Polymorphs for Solubility and Stability
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Solution Overview
Problem
There is a need for additional stable and soluble solid state forms of Bardoxolone methyl to improve its processing properties, bioavailability, and shelf-life for treating conditions like pulmonary hypertension and kidney diseases, as existing forms have limitations in solubility and stability.
Innovation Solution
The development of crystalline polymorphs of Bardoxolone methyl, specifically Forms C, D, and E, characterized by distinct X-ray powder diffraction patterns and Raman spectra, which offer improved chemical stability, solubility, and handling characteristics, allowing for the creation of pharmaceutical compositions with enhanced properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If existing crystalline forms of Bardoxolone methyl are used, then structural stability is achieved, but solubility and bioavailability are limited
Solution Approach 1:
The patent applies parameter changes by discovering and characterizing three distinct crystalline polymorphs (Forms C, D, and E) of Bardoxolone methyl, each with different crystal structures and physical properties. By changing the crystalline form parameter, the invention achieves both structural stability and improved solubility/bioavailability compared to previously known forms.
Solution Approach 2:
The patent creates composite crystalline structures by forming specific polymorphic forms with defined molecular arrangements. Each polymorph represents a composite arrangement of Bardoxolone methyl molecules in distinct crystal lattices, yielding different solubility and stability profiles while maintaining chemical identity.
2Ease of manufacture
If additional solid state forms are developed, then processing and handling characteristics are improved, but formulation complexity increases
Solution Approach 1:
The invention changes the physical state parameter by developing three distinct crystalline polymorphs with different processing and handling characteristics. Each form offers unique advantages for manufacturing operations such as compression, dissolution, and storage, allowing formulation scientists to select the optimal form for specific processing requirements without increasing chemical complexity.
3Duration of action of stationary object
If new polymorphic forms are discovered, then shelf-life and stability are improved, but characterization and quality control difficulty increases
Solution Approach 1:
The patent employs spectroscopic characterization methods including Raman spectroscopy and infrared absorption to detect and distinguish between different polymorphic forms. These analytical techniques provide unique spectral fingerprints for each polymorph, enabling reliable quality control and characterization despite the increased complexity of having multiple stable forms.
Solution Approach 2:
The invention replaces physical inspection methods with advanced analytical techniques such as X-ray diffraction, Raman spectroscopy, and infrared absorption for polymorph characterization. This substitution enables precise detection and measurement of crystal structures, facilitating quality control while improving shelf-life through stable polymorphic forms.
Data Source
AI summary
Disclosed are crystalline polymorphs of Bardoxolone methyl, and pharmaceutical compositions thereof.