Granted Patent B2

US 12,698,348 · App. 18/246,284 · Granted Aug 4, 2026

Inventors: Vincent D. Antle (Olate, KS); Andre Fernandes (Loures, PT); Mariana Rodrigues (Loures, PT); Claudio Vilela (Loures, PT)

Assignee: CyDex Pharmaceuticals, Inc.

C08B37/0012B01D3/145B01D61/027B01D61/58B01D69/02B01J20/20B01J20/28016B01J20/3071B01J20/3416C08B37/0003B01D61/145B01D2311/04B01D2311/06B01D2315/16

Abstract

Claims (37)

1 . A process for preparing an alkylated cyclodextrin composition, the process comprising:

(a) mixing a starting cyclodextrin with an alkylating agent to form a reaction milieu comprising an alkylated cyclodextrin;

(b) conducting a first one or more separations to form a first solution comprising the alkylated cyclodextrin, wherein the one of more separations comprises diafiltration through an ultrafiltration membrane;

(c) treating the first solution with an activated carbon to produce a second alkylated cyclodextrin solution; and

(d) conducting a second one or more separations to form a third alkylated cyclodextrin solution, wherein the one or more separations comprises nanofiltration through a nanofiltration membrane;

wherein the alkylated cyclodextrin is a sulfoalkyl ether cyclodextrin of Formula (II):

wherein p is 4, 5, or 6, and R 1 is independently selected at each occurrence from —OH or —O—(C 2 -C 6 alkylene)-SO 3 − -T, wherein T is independently selected at each occurrence from pharmaceutically acceptable cations, provided that at least one R 1 is —OH and at least one R 1 is O—(C 2 -C 6 alkylene)-SO 3 − -T.

2 . The process of claim 1 , wherein solvent is added to dilute the reaction milieu formed in step (a) prior to conducting the first one or more separations.

3 . The process of claim 2 , wherein the solvent is water.

4 . The process of claim 1 , wherein the concentration of the alkylated cyclodextrin in step (b) is less than 10% (w/w) prior to the first one or more separations.

5 . The process of claim 1 , wherein the concentration of the alkylated cyclodextrin in step (b) is from about 3% (w/w) to about 8% (w/w) prior to the first one or more separations.

6 . The process of claim 1 , wherein the ultrafiltration membrane in step (b) has a molecular weight cut-off (MWCO) of about 1000 Da or lower.

7 . The process of claim 1 , wherein the ultrafiltration membrane in step (b) has a MWCO of about 500 to about 1000 Da.

8 . The process of claim 1 , wherein the activated carbon of step (c) is prepared by a method comprising the step of subjecting the activated carbon to an initial carbon washing process comprising adding a portion of the first solution comprising the alkylated cyclodextrin from step (b) to the carbon, soaking the carbon in the first solution, and eluting and discarding the solution; and, wherein the activated carbon of step (c) is further subjected to a washing process comprising flowing water over the carbon after the initial carbon washing process and eluting the water.

9 . The process of claim 8 , wherein the eluted wash water has a residual conductivity of 10 μS/cm or less; or wherein the activated carbon is phosphate free; or wherein the activated carbon is steam activated; or wherein the activated carbon is granular.

10 . The process of claim 1 , wherein the concentration of the alkylated cyclodextrin in the second alkylated cyclodextrin solution introduced into step (d) is from about 3% (w/w) to about 8% (w/w).

11 . The process of claim 1 , wherein the concentration of the alkylated cyclodextrin in the second alkylated cyclodextrin solution introduced into step (d) is from about 4% (w/w) to about 7% (w/w).

12 . The process of claim 1 , wherein the nanofiltration membrane in step (d) has a MWCO of about 500 Da or lower.

13 . The process of claim 1 , wherein the nanofiltration membrane in step (d) has a MWCO of about 150-500 Da.

14 . The process claim 1 , wherein the nanofiltration of step (d) is conducted for a period of 30 minutes to 12 hours.

15 . The process of claim 1 , wherein the nanofiltration of step (d) is conducted for a period of about 1 hour to about 3 hours.

16 . The process of claim 1 , wherein the concentration of the alkylated cyclodextrin in the third alkylated cyclodextrin solution is from about 10% (w/w) to about 25% (w/w).

17 . The process of claim 1 , further comprising concentrating the third alkylated cyclodextrin solution for a period of about 2 hours to about 24 hours to form a fourth alkylated cyclodextrin solution.

18 . The process of claim 1 , further comprising concentrating the third alkylated cyclodextrin solution for a period of about 9 hours to form a fourth alkylated cyclodextrin solution.

19 . The process of claim 17 , wherein the concentrating the third alkylated cyclodextrin solution is performed by distillation.

20 . The process of claim 17 , wherein the concentration of the fourth alkylated cyclodextrin solution is from about 30% (w/w) to about 70% (w/w).

21 . The process of claim 1 , further comprising removing the solvent from the fourth alkylated cyclodextrin solution to form a solid alkylated cyclodextrin, wherein the solvent is removed by distillation, lyophilization, or spray-drying.

22 . The process of claim 21 , wherein the solid alkylated cyclodextrin comprises less than 500 ppm of a phosphate.

23 . The process of claim 21 , wherein the solid alkylated cyclodextrin comprises less than 0.05% (w/w) of a chloride.

24 . The process of claim 21 , wherein the solid alkylated cyclodextrin comprises less than 0.002% (w/w) of a chloride.

25 . The process of claim 1 , wherein the process comprises preparing a single batch of alkylated cyclodextrin wherein the initial cyclodextrin has a mass greater than 275 kg.

26 . The process of claim 1 , wherein the alkylated cyclodextrin has an average degree of substitution of 2 to 9.

27 . The process of claim 1 , wherein the alkylated cyclodextrin has an average degree of substitution of 6 to 7.5.

28 . The process of claim 1 , wherein R 1 is independently selected at each occurrence from —OH or —O—(C 4 alkylene)-SO 3 − -T, and -T is Na + at each occurrence.

29 . The process of claim 21 , further comprising combining the solid alkylated cyclodextrin with one or more excipients.

30 . The process of claim 21 , further comprising combining the solid alkylated cyclodextrin with an active agent.

31 . A product prepared by the process of claim 1 .

Assignments (3)

Continuity (2)

References Cited (351)