Compound (I) Solid Forms for Polymorph Selection and Stability
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Solution Overview
Problem
The identification and selection of solid forms of pharmaceutical compounds like {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid (Compound (I)) are complex due to their impact on physical and chemical properties, affecting processing, stability, and bioavailability, with potential issues arising from polymorphism and multiple-component forms.
Innovation Solution
The development of specific solid forms, including single-component crystal forms, multiple-component crystal forms, and amorphous forms of Compound (I), such as Forms A, B, and C, characterized by unique X-ray powder diffraction patterns and thermal properties, ensuring high purity and stability, which are used in pharmaceutical compositions for treating anemia.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If multiple solid forms (polymorphs, salts, solvates, co-crystals) are identified for Compound (I), then the options for optimizing pharmaceutical properties increase, but the complexity of selection and characterization increases
Solution Approach 1:
The patent segments the solid form landscape into distinct categories (polymorphs, salts, solvates, co-crystals, amorphous forms) with specific characterization criteria for each, allowing systematic evaluation rather than treating all solid forms as a single complex problem
Solution Approach 2:
The patent changes physical and chemical parameters (crystalline vs. amorphous, different solvent molecules, different counterions) to generate diverse solid forms with optimized properties, while establishing systematic methods to characterize and select among them
2Stability of the object's composition
If crystalline solid forms are selected for physical and chemical stability, then stability is improved, but dissolution rate and bioavailability may be reduced
Solution Approach 1:
The patent changes the physical state parameter from crystalline to amorphous, which eliminates the crystalline lattice structure that provides stability but also hinders dissolution, thereby achieving enhanced dissolution rate and bioavailability while maintaining acceptable stability through other means
Solution Approach 2:
The patent creates composite solid forms such as co-crystals and salt-solvate combinations that integrate multiple components with complementary properties, achieving both stability from the crystalline structure and improved dissolution through the specific composition and intermolecular interactions
3Productivity
If amorphous solid forms are selected for enhanced dissolution profile, then dissolution rate is improved, but physical stability may be reduced
Solution Approach 1:
The patent uses stabilizing excipients and formulation strategies as intermediaries that interact with the amorphous solid form to prevent crystallization and degradation, thereby maintaining the dissolution advantages of the amorphous state while compensating for its inherent physical instability
4Manufacturing precision
If solid forms with high purity are developed, then pharmaceutical quality is improved, but the complexity of characterization and validation increases
Solution Approach 1:
The patent segments the characterization process into form-specific protocols (XRPD for crystalline, DSC/TGA for thermal properties, NMR for molecular environment) that can be applied systematically to each solid form type, making the overall validation process more manageable despite the diversity of forms
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
These solid forms provide enhanced stability, purity, and bioavailability, facilitating effective treatment of anemia and other conditions by maintaining consistent pharmaceutical properties and reducing impurity levels.
Implementation Method 1
crystalline Compound (I), such as Form A, has an X-ray powder diffraction pattern as shown in FIG. 1
Implementation Method 2
X-ray powder diffraction pattern comprising one, two, three, four, or five peaks at approximately 18.1, 20.3, 22.9, 24.0, and 26.3°2θ
Implementation Method 3
crystalline Compound (I), such as Form A, has a peak maximum temperature in a DSC thermogram at about 175.8° C.
Implementation Method 4
single-component and multiple-component (e.g., salts, solvates, hydrates) solid forms comprising Compound (I)
Data Source
AI summary
Provided herein are solid forms comprising {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, compositions comprising the solid forms, methods of making the solid forms and methods of their use for the treatment of various diseases and/or disorders.