Crystalline form, and process for its production
Provided herein is a crystalline form (Form A) of a salt of a compound of formula (I) as defined herein. The present disclosure also relates to processes for the production of Form A of the salt, and to pharmaceutical compositions and therapeutic methods involving the salt and crystalline Form A.
1 . A crystalline form of the methanesulfonate salt of the compound of formula (I):
wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at each of 16.5, 22.4, 22.7, 23.3 and 24.1 degrees 2θ±0.2 2θ as measured by X-ray powder diffraction.
2 . The crystalline form as claimed in claim 1 , wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at one or more of 8.4, 10.5, 14.6, 15.1, 15.5, 16.8, 17.3 and 21.4 degrees 2θ±0.2 2θ as measured by X-ray powder diffraction.
3 . The crystalline form as claimed in claim 2 , wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at each of 8.4, 10.5, 14.6, 15.1, 15.5, 16.5, 16.8, 17.3, 21.4, 22.4, 22.7, 23.3 and 24.1 degrees 2θ±0.2 2θ as measured by X-ray powder diffraction.
4 . The crystalline form as claimed in claim 1 , wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising peaks at each of 8.4, 10.5, 13.2, 14.6, 15.1, 15.5, 15.9, 16.5, 16.8, 17.3, 18.4, 19.3, 20.3, 21.4, 22.0, 22.4, 22.7, 23.3, 24.1, 24.6 and 25.4 degrees 2θ±0.2 2θ as measured by X-ray powder diffraction.
5 . The crystalline form as claimed in claim 1 , wherein the crystalline form has a differential scanning calorimetry profile showing an endothermic peak with peak onset at 291° C.±5° C. and peak at 292° C.±5° C.
6 . The crystalline form as claimed in claim 1 , wherein the crystalline form has a differential scanning calorimetry profile showing an endothermic peak with peak onset at 291° C.±2° C.
7 . The crystalline form as claimed in claim 1 , wherein the crystalline form exhibits loss of not more than 0.3% mass during heating to 250° C. when subjected to thermogravimetric analysis.
8 . The crystalline form as claimed in claim 1 , wherein the crystalline form is unsolvated.
9 . The crystalline form as claimed in claim 1 , wherein the methanesulfonate salt of the compound of formula (I) has a purity of at least 98% by mass.
10 . A pharmaceutical composition comprising:
a crystalline form of the methanesulfonate salt of the compound of formula (I) as claimed in claim 1 ; and
a pharmaceutically acceptable excipient and/or carrier.
11 . The pharmaceutical composition of claim 10 , wherein at least 90% by mass of the methanesulfonate salt of the compound of formula (I) in the pharmaceutical composition is in the crystalline form.
12 . The pharmaceutical composition of claim 10 , wherein at least 98% by mass of the methanesulfonate salt of the compound of formula (I) in the pharmaceutical composition is in the crystalline form.
13 . The pharmaceutical composition of claim 10 , wherein the methanesulfonate salt of the compound of formula (I) has a purity of at least 98% by mass.
14 . A method of treating, preventing and/or reducing one or more symptoms of a neurological condition in a subject, comprising administering a therapeutically effective amount of a crystalline form as claimed in claim 1 to the subject.
15 . The method as claimed in claim 14 , wherein the neurological condition is a neurodegenerative disease or disorder.
16 . The method as claimed in claim 15 , wherein the neurodegenerative disease or disorder is selected from the group consisting of Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Creutzfeldt-Jacob disease and its variant associated with “mad cow” disease, Huntington's disease, dementia with Lewy body formation, multiple system atrophy, Hallerboden-Spatz disease, diffuse Lewy body disease, fatal familial insomnia, Gertsmann Straussler Sheinker disease, hereditary cerebral haemorrhage with amyloidosis-Dutch type, multiple sclerosis, tauopathies, motor neuron disease and prion diseases.
17 . The method as claimed in claim 15 , wherein the neurodegenerative disease or disorder is selected from the group consisting of multiple system atrophy and Parkinson's disease.
18 . A process for producing a crystalline form as claimed in claim 1 , comprising:
subjecting the methanesulfonate salt of the compound of formula (I):
to crystallisation using an alcoholic solvent.
19 . The process as claimed in claim 18 , wherein the alcoholic solvent is a methanolic solvent.
20 . The process as claimed in claim 19 , wherein the alcoholic solvent is aqueous methanol in a methanol:water volume:volume ratio in the range of from 2:1 to 1:1.
21 . The crystalline form as claimed in claim 3 , wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising one or more additional peaks at 13.2, 15.9, 18.4, 19.3, 20.3, 22.0, 24.6 and 25.4 degrees 2θ±0.2 2θ as measured by X-ray powder diffraction.