CRYSTALLINE FORM OF ISAVUCONAZONIUM SULFATE AND A PROCESS FOR ITS PREPARATION

1 . A crystalline form of isavuconazonium sulfate (Form GL-1) characterized by one or more data selected from the group consisting of: an X-ray powder diffraction (XRPD) pattern having peaks at 6.45, 7.25, 15.98, 16.87, 17.25 and 20.93±0.2 degrees 2-theta; an IR (infra-red) spectrum having main bands at about 3412.33, 2432.59, 1756, 1578.51, 1447.24, 1379.27, 1325.65, 1305, 1216.36, 1116.29, 1063.94, 926.77, 894.63, 847.74, 819.96, 765.38 and 696.25±2 cm −1 ; and a thermogravimetric Analysis (TGA) thermogram showing a weight loss of about 6.56% up to 150° C. determined over a temperature range of 0° C. to 250° C., and a heating rate of 10° C./min.

2 . The crystalline form of isavuconazonium sulfate (Form GL-1) according to claim 1 , wherein the crystalline form is further characterized by the XRPD pattern having one or more additional peaks at 12.5, 17.83, 21.99 and 22.56±0.2 degrees 2-theta.

3 . The crystalline form of isavuconazonium sulfate (Form GL-1) characterized by an X-ray powder diffraction (XRPD) pattern substantially as shown in FIG. 1 .

4 . The crystalline form of isavuconazonium sulfate (Form GL-1) according to claim 1 , wherein the crystalline form is further characterized by an IR spectrum as shown in FIG. 2 .

5 . The crystalline form of isavuconazonium sulfate (Form GL-1) according to claim 1 , wherein the crystalline form is further characterized by a TGA thermogram substantially as shown in FIG. 3 .

6 . (canceled)

7 . (canceled)

8 . The crystalline form of isavuconazonium sulfate (Form GL-1) according to claim 1 , wherein the crystalline form comprises Epimer I and Epimer II represented by the following structures in a ratio of 1:1;

9 . The crystalline form of isavuconazonium sulfate (Form GL-1) according to claim 1 , wherein the crystalline form contains an impurity selected from the compounds of formulae IV, VI, VII, VIII, IX, X or XI represented below by their chemical structures:

in an amount less than about 0.2% w/w.

10 . A process for the preparation of a crystalline form of isavuconazonium sulfate (Form GL-1), comprising:

(a) providing a reaction mixture comprising isavuconazonium sulfate and a solvent system comprising a nitrile solvent and water;

(b) stirring the reaction mixture of step (a) to precipitate isavuconazonium sulfate; and

(c) isolating isavuconazonium sulfate as obtained in step (b) in a crystalline form (Form GL-1);

wherein the crystalline form of isavuconazonium sulfate (Form GL-1) is characterized by one or more data selected from the group consisting of: an X-ray powder diffraction (XRPD) pattern having peaks at 6.45, 7.25. 15.98, 16.87, 17.25 and 20.93±0.2 degrees 2-theta; an IR (infra-red) spectrum having main bands at about 3412.33, 2432.59, 1756, 1578.51, 1447.24, 1379.27, 1325.65, 1305, 1216.36, 1116.29, 1063.94, 926.77, 894.63, 847.74, 819.96, 765.38 and 696.25±2 cm −1 ; and a thermogravimetric Analysis (TGA) thermogram showing a weight loss of about 6.56% up to 150° C. determined over a temperature range of 0° C. to 250° C., and a heating rate of 10° C./min.

11 . The process according to claim 10 , wherein the nitrile solvent is selected from the group consisting of acetonitrile, propionitrile and isobutyronitrile.

12 . The process according to claim 11 , wherein the nitrile solvent is acetonitrile.

13 . The process according to claim 10 , wherein the step (a) is carried out at a temperature of about 0° C. to about 25° C.

14 . (canceled)

15 . (canceled)

16 . (canceled)

17 . A method for the treatment of fungal infections comprising administering a therapeutically effective amount of a crystalline form of isavuconazonium sulfate (Form GL-1) to a subject in need thereof, wherein the fungal infection is mucormycosis or invasive aspergillosis;

wherein the crystalline form of isavuconazonium sulfate (Form GL-1) is characterized by one or more data selected from the group consisting of: an X-ray powder diffraction (XRPD) pattern having peaks at 6.45, 7.25, 15.98, 16.87, 17.25 and 20.93±0.2 degrees 2-theta; an IR (infra-red) spectrum having main bands at about 3412.33, 2432.59, 1756, 1578.51, 1447.24, 1379.27, 1325.65, 1305, 1216.36, 1116.29, 1063.94, 926.77, 894.63, 847.74, 819.96, 765.38 and 696.25±2 cm −1 ; and a thermogravimetric Analysis (TGA) thermogram showing a weight loss of about 6.56% up to 150° C. determined over a temperature range of 0° C. to 250° C., and a heating rate of 10° C./min.