Solid forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino} acetic acid
Inventors
Ranjan, Sudhir • Wang, Xiaoyang
Assignees
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Publication Number
US-11524939-B2
Publication Date
2022-12-13
Expiration Date
Abstract
Provided herein are solid forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid (Vadadustat, Code: AKB-6548, Compound 1), compositions comprising such solid forms, and methods of making and using thereof.
Core Innovation
The disclosure relates to solid forms of Vadadustat (Compound 1), including Solid Form D, Solid Form E, Solid Form F, Solid Form H_B, Solid Form S_A, Solid Form S_B, Solid Form S_C, Solid Form S_D, Solid Form S_E, and Solid Form S_F. The solid forms are defined by X-ray powder diffraction patterns comprising specified peaks at 2θ values with ±0.2° tolerance and by XRPD patterns substantially in accordance with referenced figures.
The disclosure identifies specific solid forms and solvate forms so that they are distinguished and characterized by defined XRPD peak sets, and it further describes physicochemical characterization including DSC and TGA behavior for selected forms. Some solid forms are further characterized as anhydrous or unsolvated, and certain solid forms include optional DSC thermal events as described.
The solid forms include crystalline solvates with specified solvent identity and stoichiometry, including 1,4-dioxane solvates and dimethylacetamide solvates. Solid Form S_B is described as a crystalline 1,4-dioxane solvate with XRPD peak sets, a Compound 1:1,4-dioxane composition of about 1:1.4, and thermal and gravimetric characterization, while Solid Form S_E is described as a dimethylacetamide solvate with XRPD substantially matching FIG. 28 and DSC around approximately 79.2–80.0°C.
Claims Coverage
The independent claim covers a solid form of Compound 1 defined by XRPD peak sets, with ten named solid-form options. The inventive features center on XRPD-defined selection among Solid Form D, Solid Form E, Solid Form F, Solid Form H_B, Solid Form S_A, Solid Form S_B, Solid Form S_C, Solid Form S_D, Solid Form S_E, and Solid Form S_F.
X-ray powder diffraction-defined solid form selection
A solid form of Compound 1 selected from the group consisting of Solid Form D, Solid Form E, Solid Form F, Solid Form H_B, Solid Form S_A, Solid Form S_B, Solid Form S_C, Solid Form S_D, Solid Form S_E, and Solid Form S_F, where each solid form is defined by an X-ray powder diffraction pattern comprising specified peaks at listed 2θ values and/or an X-ray powder diffraction pattern substantially in accordance with referenced figures.
Solid form D specified by multiple XRPD peak sets
Solid Form D of Compound 1 having an X-ray powder diffraction pattern comprising peaks at 7.9, 14.4, 14.8, 15.9, and 23.9±0.2° 2θ; 5.9, 11.8, 16.8, 24.1, and 26.9±0.2° 2θ; 6.6, 7.9, 13.4, 15.9, 20.1, and 24.5±0.2° 2θ; or substantially in accordance with FIG. 1.
Solid form E specified by XRPD peak lists
Solid Form E of Compound 1 having an X-ray powder diffraction pattern comprising peaks at 21.3, 22.8, 23.7, 27.0, and 27.7±0.2° 2θ; 16.4, 22.8, 23.6, 27.0, and 27.7±0.2° 2θ; or substantially in accordance with FIG. 4.
Solid form F specified by XRPD peak lists
Solid Form F of Compound 1 having an X-ray powder diffraction pattern comprising peaks at 8.5, 15.3, 18.5, 21.3, and 22.5±0.2° 2θ; 4.2, 12.7, 19.5, 25.9, and 29.9±0.2° 2θ; or substantially in accordance with FIG. 7.
Solid form H_B specified by XRPD peak lists
Solid Form H_B of Compound 1 having an X-ray powder diffraction pattern comprising peaks at 14.6, 15.3, 18.5, 20.4, and 28.1±0.2° 2θ; 16.0, 20.4, 26.8, 28.1, and 29.6±0.2° 2θ; 7.9, 14.6, 16.0, 17.6, and 28.1±0.2° 2θ; or substantially in accordance with FIG. 13.
Solid forms S_A, S_B, S_C, S_D, S_E, S_F specified by XRPD peak lists
Solid Form S_A, Solid Form S_B, Solid Form S_C, Solid Form S_D, Solid Form S_E, or Solid Form S_F of Compound 1, where each solid form is defined by one or more XRPD peak lists with specified 2θ values and/or XRPD patterns substantially in accordance with FIG. 16, FIG. 19, FIG. 24, FIG. 25, FIG. 28, and FIG. 31, as applicable.
The claim coverage is directed to Vadadustat (Compound 1) solid forms by defining each named solid form through characteristic XRPD peak patterns and, for some forms, correspondence to specific figures. The core inventive concept is selection of a Compound 1 solid form based on its XRPD-defined pattern.
Stated Advantages
High purity of the described solid forms, including high-purity levels reported by HPLC.
Substantial absence of other solid forms, with specified wt% limits.
High crystallinity for Solid Form S_C, S_D, S_E, and S_F.
Defined XRPD peak sets for Solid Form S_E of Compound 1 (vadadustat) as a dimethylacetamide solvate, with XRPD substantially matching FIG. 28.
Defined DSC endotherm onset and peak around approximately 79.2–80.0°C for Solid Form S_E.
Documented Applications
An oral dosage form comprising the solid form described in claim 1.
Characterization and identification of Solid Form S_E of Compound 1 (vadadustat) as a dimethylacetamide solvate using XRPD and DSC.
Use of referenced XRPD matching (FIG. 28) to characterize Solid Form S_E among multiple solid forms including adjacent solid forms.
Compound 1 (Vadadustat) is described in the context of renal anemia associated with chronic kidney disease.
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