Crystal forms of 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate
Inventors
Buckley, Neil • Belmont, Dan • BETHUNE, Sarah • DIAZ, Krista
Assignees
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Publication Number
US-12065410-B2
Publication Date
2024-08-20
Expiration Date
Abstract
The invention provides polymorphs of a compound of Formula (X):The invention also provided pharmaceutical compositions containing polymorphs of the compound and methods treating conditions in a subject by providing polymorphs of the compound.
Core Innovation
The disclosed invention relates to crystallographic polymorphs of a compound of Formula (X), identified as CV-8972, including Form A to Form E polymorphs. Form A is described as a stable monohydrate, while other polymorphs include anhydrous variants and salts, including hydrochloride and tri-hydrochloride (1:3 stoichiometry). The identity of Form A is linked to specific solid-state characterization results, including DSC thermograms and TGA thermograms.
The disclosure addresses the ability to provide a specific polymorph solid form of CV-8972 with predictable, defined characterization, including stability under ambient temperature/relative humidity conditions. Screening and characterization show conversion behavior between polymorphs, including Form E to Form A and conversion of D/E to Form A. The invention therefore provides a defined Form A polymorph suitable for pharmaceutical development rather than an unspecified mixture of polymorphic forms.
The disclosure further provides pharmaceutical compositions that comprise the Form A polymorph of the compound of Formula (X). The Form A polymorph is defined by DSC endothermic peaks, including about 85.3 °C and about 214.6 °C, and by TGA dehydration and weight loss behavior, including dehydration over a defined temperature range with about 3.46% weight loss. The compositions include defined salt and hydration states, including hydrochloride and monohydrate, and can be described as substantially free of other polymorphs (Form B–E) with characterization matching FIG. 5.
Claims Coverage
The independent claims identify a pharmaceutical composition comprising a Form A polymorph of a compound of Formula (X), with Form A defined by DSC thermogram features, TGA thermogram features, and/or substantial accordance with FIG. 5. The main inventive features are centered on the Form A polymorph specification using DSC and TGA criteria, and optionally on polymorph exclusion and characterization alignment to FIG. 5.
Form A polymorph defined by DSC endothermic peaks
A pharmaceutical composition comprising a Form A polymorph of a compound of Formula (X), wherein the Form A polymorph has an endothermic peak at about 85.3 ° C. (+5 ° C.) and at about 214.6 ° C. (±15 ° C.) in a differential scanning calorimetry (DSC) thermogram.
Form A polymorph defined by TGA dehydration and weight loss
A pharmaceutical composition comprising a Form A polymorph of a compound of Formula (X), wherein the Form A polymorph exhibits a dehydration at about 25.9 ° C. to about 150.0 ° C. with a weight loss of about 3.46% in a thermogravimetric analysis (TGA).
Form A polymorph characterized by TGA thermogram substantially in accordance with FIG. 5
A pharmaceutical composition comprising a Form A polymorph of a compound of Formula (X), wherein the Form A polymorph has a TGA thermogram substantially in accordance with FIG. 5.
Form A polymorph characterized by DSC thermogram substantially in accordance with FIG. 5
A pharmaceutical composition comprising a Form A polymorph of a compound of Formula (X), wherein the Form A polymorph has a DSC thermogram substantially in accordance with FIG. 5.
Claim coverage is provided for pharmaceutical compositions containing a Form A polymorph of the Formula (X) compound, with Form A defined through DSC endothermic peak positions, TGA dehydration behavior with specific weight loss, and/or substantial accordance of DSC and/or TGA thermograms with FIG. 5. The dependent claims further narrow the compositions by specifying salt/hydration states and excluding other polymorphs (Form B–E) as substantially free.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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