POLYMORPHS OF THE MESYLATE SALT OF LINAPRAZAN GLURATE
The present invention relates to polymorphs of the mesylate salt of 5-{2-[({8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridine-6-yl}carbonyl)-amino]ethoxy}-5-oxopentanoic acid (linaprazan glurate), more specifically Form A and Form B of the mesylate salt of linaprazan glurate. The invention also relates to pharmaceutical compositions comprising such polymorphs, and to the use of these polymorphs in the treatment or prevention of gastrointestinal inflammatory diseases or gastric acid related diseases, in particular erosive gastroesophageal reflux disease (cGERD).
1 . A crystalline mesylate salt of linaprazan glurate.
2 . The crystalline mesylate salt of linaprazan glurate according to claim 1 , wherein the crystalline mesylate salt is stable at a relative humidity of 94% at room temperature.
3 . The crystalline mesylate salt of linaprazan glurate according to claim 1 , which is a non-stoichiometric hydrate.
4 . The crystalline mesylate salt of linaprazan glurate according to claim 3 , which is Form A, having an XRPD pattern, obtained with CuKα1-radiation, with at least two peaks at °2θ values selected from the list consisting of 7.5±0.2, 9.1±0.2, 12.1±0.2, 16.0±0.2, 17.6±0.2, 21.9, 24.3±0.2, 24.6±0.2 and 25.3±0.2.
5 . The crystalline mesylate salt of linaprazan glurate according to claim 4 , wherein Form A has an XRPD pattern, obtained with CuKα1-radiation, with at least peaks at °2θ values of 7.5±0.2, 9.1±0.2, 16.0±0.2 and 17.6±0.2.
6 . The crystalline mesylate salt of linaprazan glurate according to claim 4 , wherein Form A has an XRPD pattern, obtained with CuKα1-radiation, with at least peaks at °2θ values of 7.5±0.2, 9.1±0.2, 12.1±0.2, 16.0±0.2, 17.6±0.2, 21.9, 24.3±0.2, 24.6±0.2 and 25.3±0.2.
7 . The crystalline mesylate salt of linaprazan glurate according to claim 3 , which is Form A, having an XRPD pattern, obtained with CuKα-radiation, substantially as shown in FIG. 1 or FIG. 2 .
8 . The crystalline mesylate salt of linaprazan glurate according to claim 4 , wherein Form A has a DSC curve comprising an endotherm between about 175° C. and about 200° C.
9 . The crystalline mesylate salt of linaprazan glurate according to claim 3 , which is Form B, having an XRPD pattern, obtained with CuKα1-radiation, with at least two peaks at °2θ values selected from the list consisting of 6.4±0.2, 7.0±0.2, 9.4±0.2, 14.6±0.2, 15.6±0.2, 18.2±0.2, 21.8±0.2, 23.4±0.2, 24.4±0.2 and 25.4±0.2.
10 . The crystalline mesylate salt of linaprazan glurate according to claim 9 , wherein Form B has an XRPD pattern, obtained with CuKα1-radiation, with at least peaks at °2θ values of 6.4±0.2, 7.0±0.2, 9.4±0.2 and 15.6±0.2.
11 . The crystalline mesylate salt of linaprazan glurate according to claim 9 , wherein Form B has an XRPD pattern, obtained with CuKα1-radiation, with at least peaks at °2θ values of 6.4±0.2, 7.0±0.2, 9.4±0.2, 15.6±0.2, 18.2±0.2, 23.4±0.2 and 25.4±0.2.
12 . The crystalline mesylate of linaprazan glurate according to claim 3 , which is Form B, having an XRPD pattern, obtained with CuKα-radiation, substantially as shown in FIG. 3 .
13 . The crystalline mesylate salt of linaprazan glurate according to claim 9 , wherein Form B has a DSC curve comprising an endotherm between about 100° C. and about 130° C.
14 . The crystalline mesylate salt of linaprazan glurate according to claim 1 , having a crystallinity of greater than 99%.
15 . A pharmaceutical composition comprising a therapeutically effective amount of a crystalline mesylate salt of linaprazan glurate according to claim 1 , in association with one or more pharmaceutically acceptable excipients.
16 . The crystalline mesylate salt of linaprazan glurate according to claim 1 , for use in therapy.
17 . The crystalline mesylate salt of linaprazan glurate according to claim 1 , for use in the treatment or prevention of a gastrointestinal inflammatory disease or a gastric acid related disease.
18 . The crystalline mesylate salt of linaprazan glurate for use according to claim 17 , wherein the gastrointestinal inflammatory disease or the gastric acid related disease is gastritis, gastroesophageal reflux disease (GERD), erosive gastroesophageal reflux disease (eGERD), H. pylori infection, Zollinger-Ellison syndrome, peptic ulcer disease (including gastric ulcers and duodenal ulcers), bleeding gastric ulcer, symptoms of gastroesophageal reflux disease (including heartburn, regurgitation and nausea), gastrinoma or acute upper gastrointestinal bleeding.
19 . The crystalline mesylate salt of linaprazan glurate for use according to claim 17 , wherein the gastrointestinal inflammatory disease or the gastric acid related disease is erosive gastroesophageal reflux disease (eGERD).