Morphic forms of G1T38 and methods of manufacture thereof
Inventors
Smith, Alexander • White, Hannah S. • Andres, Patricia • Sun, Xufeng • Zhu, Lei • Vlahova, Petinka I.
Assignees
Pharmacosmos Holding AS • Pharmacosmos AS • Curia Global Inc
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Publication Number
US-12139494-B2
Publication Date
2024-11-12
Expiration Date
Abstract
This invention provides an unexpectedly stable, highly crystalline form of the di-HCl salt of for advantageous therapeutic pharmaceutical efficacy and dosage form stability.
Core Innovation
The document relates to an isolated crystalline Form B of the di-HCl salt of G1T38 (Compound 2) for solid dosage delivery. Form B is characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three 2θ values selected from the stated ranges, and this XRPD-based definition distinguishes Form B from other morphic forms described in the document.
The document describes multiple morphic forms and reports characterization of Form B using XRPD, including peak positions, together with differential scanning calorimetry, thermogravimetric infrared, DSC/TGA, 1H NMR, XRPD indexing, and unit-cell parameters. It also describes conversion and purification of impure Form B to pure Form B, with confirmation by XRPD and TG.
The solid-state findings include moisture sorption behavior using dynamic vapor sorption, where Form B is reported as more stable than Forms A/D, as well as thermal stability and long-term stability. The document further states that Form B is unexpectedly superior for pharmaceutical development and is suitable for use in pharmaceutical compositions and combination therapies.
Claims Coverage
The independent claim covers a solid-dosage pharmaceutical composition using a pharmaceutically acceptable excipient and an isolated crystalline Form B of the di-HCl salt in a specified dosage range. The claim includes two inventive features.
Xrpd-defined crystalline form b of di-hcl salt
An isolated crystalline Form B of the di-HCl salt characterized by an XRPD pattern comprising at least three 2θ values selected from 6.5±0.2°, 9.5±0.4°, 14.0±0.2°, 14.4±0.2°, 18.1±0.2°, 19.3±0.2°, 19.9±0.2°, and 22.4±0.2°.
Solid dosage pharmaceutical composition with excipient and dose range
A pharmaceutical composition comprising a pharmaceutically acceptable excipient for solid dosage delivery and between about 10 mg and about 1,000 mg of the isolated crystalline Form B of the di-HCl salt.
Overall, the claim is directed to a solid dosage pharmaceutical composition that includes a pharmaceutically acceptable excipient and a defined amount of isolated crystalline Form B of the di-HCl salt, with Form B limited by the stated XRPD 2θ value set.
Stated Advantages
Form B is described as unexpectedly superior for pharmaceutical development.
Form B is described as highly crystalline.
Form B is described as moisture/thermal-stable.
Form B is reported to show improved stability compared with Forms A and D.
Documented Applications
Treatment of CDK4/6-dependent cellular proliferative disorders, including pRb-positive/ER+ breast cancer and CDK4/6 cancer cell inhibition.
Use in pharmaceutical compositions, including combination therapies.
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