Ivosidenib forms and pharmaceutical compositions
Inventors
Gu, Chong-Hui • SIZEMORE, JACOB PAUL • Zhang, Shijie
Assignees
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Publication Number
US-12264148-B2
Publication Date
2025-04-01
Expiration Date
Abstract
Provided are formulations of ivosidenib including a number of polymorphs. Further provided are formulations of ivosidenib containing a number of known impurities. Still further provided are stable compositions of ivosidenib.
Core Innovation
The disclosure relates to ivosidenib as a compound of Formula (I) in specific solid-state forms, including a methyl isobutyl ketone (MIBK) solvate solid state form designated Form E and anhydrous forms designated Form M, L, and N, as well as partially crystalline Pattern forms. The solid-state forms are characterized by XRPD, DSC, and TGA, including diagnostic XRPD peak positions and thermal behavior that define crystallinity status and solid-state identity.
The disclosure describes interconversion behavior among solid-state forms, including slurry processing among anhydrous forms L, M, and N toward Pattern 3, with Pattern 3 converting to Form L upon vacuum drying. It also describes conversion to solvate Form E and hydrate Form B under specified solvent conditions, with characterization supporting the resulting solid-state identity.
The disclosure further includes pharmaceutical compositions and solid dosage forms comprising one or more of the described solid-state forms of the compound of Formula (I), with impurity limits. It also places the solid forms in an impurity control context involving elemental impurities, residual solvents, potential genotoxic impurities, and named impurity structures.
Claims Coverage
The document provides coverage for two independent solid-state form claim families, with two inventive features defined primarily by XRPD peak positions and further constrained by dependent thermal and spectroscopic criteria.
Solid state form E as a MIBK solvate with specified XRPD peaks
A solid state form E of a methyl isobutyl ketone (MIBK) solvate of ivosidenib, or of a compound of Formula (I), having an x-ray powder diffraction pattern comprising peaks at 6.3±0.2° 2θ, 11.6±0.2° 2θ, 12.0±0.2° 2θ, 17.1±0.2° 2θ, and 21.0±0.2° 2θ.
Anhydrous solid state form M with specified XRPD peaks
An anhydrous solid state form M of ivosidenib, or of a compound of Formula (I), characterized by an x-ray powder diffraction pattern comprising peaks at 11.4±0.2° 2θ, 17.7±0.2° 2θ, 17.8±0.2° 2θ, 19.7±0.2° 2θ, and 21.4±0.2° 2θ.
Both independent claims are phase-fingerprint claims for specific ivosidenib solid state forms, using XRPD peak position constraints as the core defining element. Dependent claims further characterize the same forms using thermal analysis and 1H NMR features.
Stated Advantages
Provides defined analytical characterization of ivosidenib solid state forms using XRPD, DSC, and TGA, including diagnostic XRPD peak identification and thermal signatures.
Supports identity confirmation of specific solid state forms via additional constraints beyond XRPD peaks, including thermal and spectroscopic criteria.
Enables assessment of performance-related behavior through dissolution testing with calculated similarity factors (f2).
Documented Applications
Dissolution testing of spray-dried dispersion tablets spiked with crystalline Form L or Form B, including calculation of similarity factors (f2).
Pharmaceutical compositions and solid dosage forms comprising one or more of the described solid-state forms with impurity limits.
Impurity control for ivosidenib drug product intermediates, including elemental impurities, residual solvents, potential genotoxic impurities, and named impurity structures.
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