Sulfoalkyl ether cyclodextrin compositions
SAE-CD compositions are provided, along with methods of making and using the same. The SAE-CD compositions comprise a sulfoalkyl ether cyclodextrin having an absorption of less than 0.5 A.U. due to a drug-degrading agent, as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length.
1. A sulfoalkyl ether cyclodextrin (SAE-CD) composition comprising a sulfoalkyl ether cyclodextrin having less than 200 ppm of a phosphate, wherein the SAE-CD composition has an absorption of less than 0.2 A.U., as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length.
2. The SAE-CD composition of claim 1 , wherein the SAE-CD composition has an absorption of less than 0.15 A.U., as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length.
3. The SAE-CD composition of claim 1 , wherein the SAE-CD composition has an absorption of less than 0.1 A.U., as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length.
4. The SAE-CD composition of claim 1 , wherein the SAE-CD composition has an absorption of less than 0.05 A.U., as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length.
5. The SAE-CD composition of claim 1 , wherein the SAE-CD is a compound of Formula (I):
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.
6. The SAE-CD composition of claim 5 , wherein the SAE-CD has an average degree of substitution of 4.5 to 7.5.
7. The SAE-CD composition of claim 5 , 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.
8. The SAE-CD composition of claim 5 , wherein the SAE-CD is sulfobutyl ether β-cyclodextrin having the structure:
wherein:
each R is independently —H or —(CH 2 ) 4 SO 3 Na; and
the average degree of substitution of —(CH 2 ) 4 SO 3 Na is 6.0 to 7.1 per cyclodextrin molecule.
9. The SAE-CD composition of claim 1 further comprising an active agent.
10. The SAE-CD composition of claim 1 , wherein the SAE-CD composition comprises:
less than 10 ppm of a sulfoalkylating agent;
less than 0.2% wt. of an underivatized cyclodextrin;
less than 0.5% wt. of an alkali metal halide salt; and
less than 0.1% wt. of a hydrolyzed sulfoalkylating agent.
11. The SAE-CD composition of claim 1 , wherein the SAE-CD composition comprises:
less than 250 ppb of a sulfoalkylating agent;
less than 0.1% wt. of an underivatized cyclodextrin;
less than 0.1% wt. of an alkali metal halide salt; and
less than 0.08% wt. of a hydrolyzed sulfoalkylating agent.
12. A sulfoalkyl ether cyclodextrin (SAE-CD) composition comprising a sulfoalkyl ether cyclodextrin having less than 150 ppm of a phosphate, wherein the SAE-CD composition has an absorption of less than 0.2 A.U., as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length.
13. The SAE-CD composition of claim 12 , wherein the SAE-CD composition has an absorption of less than 0.2 A.U., as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length.
14. The SAE-CD composition of claim 12 , wherein the SAE-CD composition has an absorption of less than 0.15 A.U., as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length.
15. The SAE-CD composition of claim 12 , wherein the SAE-CD composition has an absorption of less than 0.1 A.U., as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length.
16. The SAE-CD composition of claim 12 , wherein the SAE-CD composition has an absorption of less than 0.05 A.U., as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the SAE-CD composition per mL of solution in a cell having a 1 cm path length.
17. The SAE-CD composition of claim 12 , wherein the sulfoalkyl ether cyclodextrin is a compound of Formula (I):
wherein:
p is 4, 5, or 6;
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.
18. The SAE-CD composition of claim 17 , wherein the SAE-CD has an average degree of substitution of 4.5 to 7.5.
19. The SAE-CD composition of claim 17 , 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.
20. The SAE-CD composition of claim 17 , wherein the SAE-CD is sulfobutyl ether β-cyclodextrin having the structure:
wherein:
each R is independently —H or —(CH 2 ) 4 SO 3 Na; and
the average degree of substitution of —(CH 2 ) 4 SO 3 Na is 6.0 to 7.1 per cyclodextrin molecule.
21. The SAE-CD composition of claim 12 further comprising an active agent.
22. The SAE-CD composition of claim 12 , wherein the SAE-CD composition comprises:
less than 10 ppm of a sulfoalkylating agent;
less than 0.2% wt. of an underivatized cyclodextrin;
less than 0.5% wt. of an alkali metal halide salt; and
less than 0.1% wt. of a hydrolyzed sulfoalkylating agent.
23. The SAE-CD composition of claim 12 , wherein the SAE-CD composition comprises:
less than 250 ppb of a sulfoalkylating agent;
less than 0.1% wt. of an underivatized cyclodextrin;
less than 0.1% wt. of an alkali metal halide salt; and
less than 0.08% wt of a hydrolyzed sulfoalkylating agent.