Crystalline forms and methods of producing crystalline forms of a compound

Inventors

Lian, Brian • Masamune, Hiroko • Barker, Geoffrey

Assignees

Viking Therapeutics Inc

Abstract

Disclosed herein are methods of crystallizing the compound of Formula I, as well as crystalline forms thereof. Crystalline forms of Formula I disclosed include the TBME solvate crystalline form, toluene solvate crystalline form, ethanol solvate crystalline form, THF solvate crystalline form, EtOAc solvate crystalline form, acetone solvate crystalline form and crystalline Form C.

Core Innovation

Crystalline forms of a compound of Formula I are disclosed as solid forms suitable for thyroid hormone receptor β (TRβ) agonist activity. The disclosure includes crystalline Form C and multiple solvate crystalline forms corresponding to TBME, toluene, ethanol, THF, EtOAc, and acetone solvates. The crystalline forms are characterized by X-ray powder diffraction (XRPD) patterns using characteristic peaks at selected 2θ values.

A method is described for obtaining the crystalline Form C by converting an amorphous form of a Formula I compound into a crystalline form through solvent/antisolvent addition and isolating the crystalline product from a second mixture. The disclosure additionally describes seeding crystallization approaches in which a seeding crystalline form of the compound of Formula I, or a solvate thereof, is added to a first solution to create a seeded mixture, followed by isolating the produced crystalline form from the seeded mixture.

The crystalline Form C is supported by solid-state characterization including XRPD peak positions, DSC melting point behavior, and TGA mass loss behavior. Stability and hygroscopicity are described using dynamic vapor sorption (DVS), including low water uptake by Form C, and absence of hydrate formation and no polymorphic transition after humidity/water exposure, as assessed by XRPD and related observations.

Claims Coverage

The document provides three independent claims, covering a crystalline Form C composition defined by XRPD characteristic peaks, and two processes to make crystalline Form C, one by solvent/antisolvent conversion from an amorphous form and one by seeding crystallization.

Across the independent claims, crystalline Form C is the central product, identified by a specified XRPD characteristic peak set, and crystalline Form C is produced either by dissolving an amorphous Formula I form followed by second-solvent addition and isolation, or by dissolving Formula I and adding a seeding crystalline form, including specified solvate seeding forms, followed by isolation.

Stated Advantages

Documented Applications