Crystalline form of Tolebrutinib
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Publication Number
US-12049463-B2
Publication Date
2024-07-30
Expiration Date
Abstract
The present disclosure relates to a novel crystalline form of Tolebrutinib (hereinafter referred to as “Compound I”) and preparation methods thereof, pharmaceutical compositions containing the crystalline form, and uses of the crystalline form for preparing BTK inhibitor drugs and drugs for treating multiple sclerosis.
Core Innovation
The disclosure describes a crystalline form of tolebrutinib, referred to as Compound I and designated Form CSI, characterized by an X-ray powder diffraction pattern using CuKα radiation with characteristic peaks at specified 2θ values. The crystalline form is further characterized by differential scanning calorimetry and thermogravimetric analysis, and is designated as an anhydrate.
The disclosure indicates that prior art produces mainly amorphous material of Compound I, which is described as having poor stability, hygroscopicity, and degradability. Form CSI is obtained and identified as a crystalline form distinguished from amorphous material, and is unexpectedly obtained while retaining the crystalline character under conditions relevant to storage and stress.
Form CSI is reported to maintain high chemical purity and the crystal form under long-term and stress/accelerated conditions, and is described as having low hygroscopicity based on dynamic vapor sorption weight gain. The disclosure also states that Form CSI supports formulation into a tablet drug product formulation with XRPD-confirmed physical stability after formulation and storage.
Claims Coverage
The independent claim set is centered on a crystalline form of Compound I defined by a CuKα XRPD pattern with specific characteristic peaks at defined 2θ values. In total, the claims describe four inventive features, including additional peak constraints, a figure-referenced XRPD pattern, and a pharmaceutical composition.
Crystalline form defined by CuKα XRPD characteristic peaks at specified 2θ values
A crystalline form of Compound I wherein an X-ray powder diffraction pattern comprises characteristic peaks at 2theta values of 7.7°±0.2°, 11.0°±0.2°, 22.8°±0.2°, 12.0°±0.2°, 16.1°±0.2°, and 18.5°±0.2° using CuKα radiation.
Crystalline form having additional at least one characteristic CuKα XRPD peak
The crystalline form of Compound I includes at least one characteristic peak at 2theta values of 13.6°±0.2°, 20.1°±0.2°, and 24.8°±0.2° using CuKα radiation.
Crystalline form defined by an XRPD pattern shown in FIG. 2
The crystalline form of Compound I is defined by an X-ray powder diffraction pattern as shown in FIG. 2 using CuKα radiation.
Pharmaceutical composition comprising therapeutically effective amount of the crystalline form
A pharmaceutical composition comprises a therapeutically effective amount of the crystalline form described in claim 1 and pharmaceutically acceptable excipients.
Overall, the claims focus on Form CSI/Compound I as a specific crystalline form defined by CuKα XRPD characteristic peaks and related XRPD pattern features, with a dependent pharmaceutical composition including pharmaceutically acceptable excipients.
Stated Advantages
Form CSI maintains high chemical purity and crystal form under long-term and stress/accelerated storage conditions.
Form CSI is described as having low hygroscopicity compared to amorphous prior art.
Form CSI shows XRPD-confirmed physical stability after formulation and storage in a tablet drug product formulation.
Documented Applications
Use of Form CSI to prepare a tablet drug product formulation, with XRPD-confirmed physical stability after formulation and storage.
Use of Form CSI for preparing BTK inhibitor drugs.
Use of Form CSI for drugs for treating multiple sclerosis (MS) / relapsing multiple sclerosis (RMS).
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