SOLID STATE FORMS OF SUGAMMADEX SODIUM
The present disclosure relates to solid state forms of Sugammadex sodium, processes for preparation thereof and pharmaceutical compositions thereof.
1 . A process for the preparation of crystalline Sugammadex sodium, comprising: crystallizing Sugammadex sodium from a mixture including water and methanol, wherein the water is present in an amount of about 1 to about 10 ml per gram of Sugammadex sodium, and the methanol is present in an amount of about 15 to about 30 ml per gram of Sugammadex sodium; and
drying the Sugammadex sodium under reduced pressure at a temperature of about 40° C. to about 80° C.
2 . The process according to claim 1 , further comprising:
(i) adding methanol to a solution of Sugammadex sodium in water at a temperature of about 45° C. to about 70° C. to form a suspension;
(ii) cooling the suspension to about 18° C. to about 40° C.; and
(iii) optionally stirring the suspension for about 0.5 to about 4 hours.
3 . The process according to claim 1 , wherein water is present in an amount of about 1 to about 5 ml per gram of Sugammadex sodium.
4 . The process according to claim 1 , wherein methanol is present in an amount of about 15 to about 28 ml per gram of Sugammadex sodium.
5 . The process according to claim 1 , wherein the volume ratio of methanol to water is about 20:1 to about 3:1.
6 . The process according to claim 2 , wherein step (i) comprises addition of methanol to the solution of Sugammadex sodium in water.
7 . The process according to claim 2 , where the solution of Sugammadex sodium in water is at a temperature of about 45° C. to about 65° C.
8 . The process according to claim 2 , wherein step (ii) comprises cooling the suspension to a temperature of about 18° C. to about 30° C.
9 . The process according to claim 8 , wherein the cooling is carried out over a period of about 0.5 to about 8 hours.
10 . The process according to claim 2 , wherein step (iii) comprises stirring the cooled suspension for about 0.5 to about 8 hours.
11 . The process according to claim 1 , further comprising isolating the Sugammadex sodium by filtration.
12 . The process according to claim 1 , wherein the drying is carried out over a period of about 4 to about 90 hours.
13 . The process according to claim 1 , wherein the drying is carried out under an inert atmosphere.
14 . The process according to claim 1 , wherein the Sugammadex sodium is dried in vacuo in an inert atmosphere under nitrogen, at a temperature of about 50° C. to about 65° C.
15 . The process according to claim 1 , further comprising combining the Sugammadex sodium with at least one pharmaceutically acceptable excipient to provide a pharmaceutical composition.
16 . The process according to claim 1 , wherein the crystalline Sugammadex sodium is crystalline Form 6 of Sugammadex sodium.
17 . The process according to claim 16 , further comprising maintaining the crystalline form 6 of Sugammadex sodium at a relative humidity of about 50 to about 100% to obtain Form 9 of Sugammadex sodium.
18 . The process according to claim 17 , further comprising maintaining the crystalline form 6 of Sugammadex sodium at room temperature to obtain Form 9 of Sugammadex sodium.
19 . The process of claim 17 , further comprising maintaining the crystalline form 6 of Sugammadex sodium at a relative humidity of about 50 to about 100% for a period of time from about 3 days to about 12 days to obtain Form 9 of Sugammadex sodium.