Crystalline forms of ozanimod and ozanimod hydrochloride, and processes for preparation thereof
Inventors
Chen, Minhua • Zhang, Xiaoyu • Zhang, Yanfeng • YANG, Chaohui • ZHAI, Xiaoting • YAN, Kaiqiang
Assignees
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Publication Number
US-11680050-B2
Publication Date
2023-06-20
Expiration Date
Abstract
The present disclosure is directed to novel crystalline forms of ozanimod and ozanimod hydrochloride, as well as preparation method thereof. Said crystalline forms of ozanimod and ozanimod hydrochloride can be used for treating autoimmune diseases, particularly used for preparing drugs for treating multiple sclerosis and ulcerative colitis. The crystalline forms of the present disclosure have one or more advantages in solubility, melting point, stability, dissolution, bioavailability and processability and provide new and better choices for the preparation of ozanimod drug product, and are very valuable for drug development.
Core Innovation
The invention relates to crystalline polymorph forms of ozanimod and crystalline Form CS1 of ozanimod hydrochloride. The document describes crystalline Form CS1, crystalline Form CS2, crystalline Form CS3, crystalline Form CS5, and crystalline Form CS6 for ozanimod, and crystalline Form CS1 for ozanimod hydrochloride.
The crystalline forms are characterized by X-ray powder diffraction, including XRPD/X-ray powder diffraction patterns with characteristic peaks expressed as 2theta values using CuKα radiation. The document provides sets of XRD characteristic peak positions for the crystalline forms, together with thermal behavior and weight-loss behavior from DSC and TGA.
The document further reports hygroscopicity using DVS and solid-state stability under controlled temperature/RH, with XRPD and HPLC purity retention. Particle size characteristics and solubility in simulated gastric and intestinal fluids are also reported, highlighting low hygroscopicity, good stability, and improved solubility/processability for drug development. The document also links the described use with multiple sclerosis and ulcerative colitis.
Claims Coverage
The independent claim is clm-00001, which defines crystalline Form CS1 of ozanimod hydrochloride by a specific XRPD characteristic-peak set expressed as 2theta values measured with CuKα radiation. Additional claims cover alternate peak sets, a pharmaceutical composition, and a method of treating ulcerative colitis.
Crystalline Form CS1 of ozanimod hydrochloride by XRPD characteristic peaks
A crystalline Form CS1 of ozanimod hydrochloride, wherein the X-ray powder diffraction pattern shows characteristic peaks at 2theta values of 26.1°±0.20°, 24.4°±0.20° and 20.1°±0.20° using CuKα radiation.
Crystalline Form CS1 of ozanimod hydrochloride with alternate XRPD peak set
The crystalline Form CS1 of ozanimod hydrochloride, wherein the X-ray powder diffraction pattern shows 1 or 2 or 3 characteristic peaks at 2theta values of 3.9°±0.20°, 21.1°±0.20° and 7.9°±0.20° using CuKα radiation.
Crystalline Form CS1 of ozanimod hydrochloride with further alternate XRPD peak set
The crystalline Form CS1 of ozanimod hydrochloride, wherein the X-ray powder diffraction pattern shows 1 or 2 or 3 characteristic peaks at 2theta values of 11.9°±0.20°, 19.6°±0.20° and 13.8°±0.20° using CuKα radiation.
Pharmaceutical composition comprising Form CS1 and a pharmaceutically acceptable carrier
A pharmaceutical composition comprises a therapeutically effective amount of crystalline Form CS1 of ozanimod hydrochloride and a pharmaceutically acceptable carrier, a diluent or an excipient.
Method of treating ulcerative colitis with Form CS1
A method of treating ulcerative colitis comprises administering to a patient in need thereof a therapeutically effective amount of crystalline Form CS1 of ozanimod hydrochloride.
Overall claim coverage focuses on defining crystalline Form CS1 of ozanimod hydrochloride by XRPD characteristic peaks at specified 2theta values under CuKα radiation. The claims also include alternate peak sets, a pharmaceutical composition, and a method of treating ulcerative colitis by administering the crystalline form.
Stated Advantages
Low hygroscopicity.
Good solid-state stability under controlled temperature/RH.
Improved solubility in simulated gastric and intestinal fluids, supporting drug development.
Documented Applications
Drug development applications are described with use connected to multiple sclerosis and ulcerative colitis.
A method of treating ulcerative colitis using a therapeutically effective amount of crystalline Form CS1 of ozanimod hydrochloride.
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