Phenylcarbamate crystalline form and method for manufacturing the same
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Publication Number
US-11795139-B2
Publication Date
2023-10-24
Expiration Date
Abstract
The present invention relates to a crystalline form of a phenyl carbamate derivative compound and a use thereof, and more particularly, to a more thermodynamically stable crystal, i.e., a Pattern 1 crystalline form, and a preparation method thereof. Amorphous and crystalline forms were prepared using various solvents, and among these, a thermodynamically stable Pattern 1 crystalline form and a pharmaceutical use of this crystalline form are provided.
Core Innovation
The invention relates to an anhydrous thermodynamically stable Pattern 1 crystalline form of a phenyl carbamate derivative, namely 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate (JBPOS0101). Pattern 1 is defined by an X-ray powder diffraction pattern with specified diffraction peaks and is characterized as a crystalline solid rather than a solvate.
Pattern 1 is further characterized by DSC and TGA behavior, including an endothermic peak around 89 to 90 °C and minimal mass loss prior to about 200 °C in thermal gravimetric analysis. Humidity resistance is emphasized, with gravimetric vapor sorption showing low mass gain over 0–90% RH and no XRPD morphological change after high-RH stress.
A solvent-based polymorph screening/manufacturing approach is described to obtain Pattern 1 from an amorphous form, and additional solvent sets are described as yielding other patterns. Competitive slurry experiments support greater thermodynamic stability, showing Pattern 1 converts preferentially from mixtures at room temperature and at 50 °C, including when compared against Pattern 3 and other patterns.
Claims Coverage
The document provides one independent claim covering a specific crystalline form defined by an X-ray powder diffraction peak list, with dependent claims refining characterization, preparation, and pharmaceutical use. The independent claim contains the core inventive definition, while the dependent claims add a DSC endothermic peak at 89 to 90 °C, a solvent-based amorphous-to-crystalline preparation concept, and use in pharmaceutical compositions for disease treatment.
Crystalline form defined by X-ray powder diffraction peak set
A crystalline form of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate having peaks of an X-ray powder diffraction pattern at specified 2θ diffraction angles listed in the claim.
DSC endothermic peak around 89 to 90 °C
The crystalline form has an endothermic peak at 89 to 90 °C when measured by differential scanning calorimetry (DSC).
Solvent process from an amorphous form to the crystalline form
A method preparing the crystalline form includes first forming an amorphous form using selected solvents and then removing those solvents, followed by treating the amorphous form with a second selected solvent set and isolating the crystalline form.
Pharmaceutical composition comprising the crystalline form
A pharmaceutical composition includes the crystalline form of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate defined by the X-ray powder diffraction peak set.
Disease treatment by administering the pharmaceutical composition
Treating a selected disease by administering the pharmaceutical composition that includes the crystalline form.
Overall, the claim set centers on defining a thermodynamically stable Pattern 1 crystalline form through an X-ray powder diffraction peak list, optionally bounded by a DSC endothermic peak at 89 to 90 °C. Further coverage extends to a solvent-based amorphous-to-crystalline preparation concept and to pharmaceutical composition and disease treatment use by administering the composition.
Stated Advantages
Strong humidity resistance, with low mass gain over 0–90% RH and no XRPD morphological change after high-RH stress.
Greater thermodynamic stability, with preferential conversion of Pattern 1 from mixtures compared with Pattern 3 and other patterns in competitive slurry experiments.
Characterized thermal and physicochemical stability supported by XRPD, DSC, TGA, and GVS measurements and by maintained XRPD morphology after humidity stress.
Documented Applications
Pharmaceutical composition use of the Pattern 1 solid for treating or preventing neurological and related disorders, including multiple sclerosis, Lou Gehrig’s disease/ALS, epilepsy, central nervous system disorders, spasticity/spasms, muscle relaxation, chronic pain, stroke, psychiatric disorders (including depression, anxiety, and bipolar disorder), memory-loss diseases, and autism spectrum/prion-related diseases.
Treating a selected disease by administering a pharmaceutical composition that includes the crystalline form.
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