Sulfoalkyl ether cyclodextrin compositions

• US 9,200,088 B2
• Filed: 03/07/2013
• Issued: 12/01/2015
• Est. Priority Date: 04/28/2008
• Status: Active Grant

• Current Assignee: CyDex Pharmaceuticals, Inc. (Ligand Pharmaceuticals, Inc.)
• Original Assignee: CyDex Pharmaceuticals, Inc. (Ligand Pharmaceuticals, Inc.)
• Inventors: Antle, Vincent D.
• Primary Examiner(s): Olson, Eric
• Application Number:
  US13/789,598
• Publication Number:
  US 20130184357A1
• Time in Patent Office: 999 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/724 Cyclodextrins
• CPC Class Codes: A61K 47/40 Cyclodextrins; Derivatives thereof
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 47/6951 using cyclodextrin cyclodextrins used as simple excipients A61K47/40
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: C08B 31/00 Preparation of derivatives of starch derivatives of amylose C08B33/00; derivatives of amylopectin C08B35/00
• CPC Class Codes: C08B 37/0012 Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
• CPC Class Codes: C08L 5/16 Cyclodextrin; Derivatives thereof

Abstract

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.

Claims

1. A sulfoalkyl ether cyclodextrin (SAE-CD) composition that can be readily mixed with an active agent, comprising a sulfoalkyl ether cyclodextrin having an average degree of substitution of 4.5 to 7.5 and less than 200 ppm of a phosphate, wherein the SAE-CD composition has an absorption of less than 0.5 A.U. due to a UV-active impurity 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.

8. The SAE-CD composition of claim 1, wherein the SAE-CD composition has an absorption of less than 0.5 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.

9. The SAE-CD composition of claim 1, wherein the SAE-CD composition has an absorption of less than about 0.25 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.

10. The SAE-CD composition of claim 1, wherein the SAE-CD composition has an absorption of less than about 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.

11. The SAE-CD composition of claim 1, comprising less than 100 ppm of a phosphate.

12. The SAE-CD composition of claim 1, wherein the sulfoalkyl ether cyclodextrin is a compound of Formula (I):

13. The SAE-CD composition of claim 12, wherein R₁ is independently selected at each occurrence from —

OH or —

OH—

O—

(C₂-C₆ alkylene)-SO₃-T, and -T is Na⁺ at each occurrence.

14. A formulation, comprising the SAE-CD composition of claim 1 and an active agent.

15. The formulation of claim 14, wherein the formulation has an active agent assay of about 98% or more when the formulation is maintained at a temperature of about 80°

C. for a period of about 120 minutes.

16. The formulation of claim 14, wherein the formulation has an active agent assay of about 99.5% or more when the formulation is maintained at a temperature of about 80°

C. for a period of about 120 minutes.

17. The formulation of claim 14, wherein the active agent is a pharmaceutically effective active agent and is present in the formulation in an effective amount.

2. A sulfoalkyl ether cyclodextrin (SAE-CD) composition that can be readily mixed with an active agent, comprising a sulfoalkyl ether cyclodextrin having an average degree of substitution of 4.5 to 7.5 and less than 200 ppm of a phosphate, wherein the SAE-CD composition has an absorption of less than 0.5 A.U. due to a UV-active drug-degrading agent that degrades aripiprazole as determined b 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.

3. A sulfoalkyl ether cyclodextrin (SAE-CD) composition that can be readily mixed with an active agent, comprising a sulfoalkyl ether cyclodextrin having an average degree of substitution of 4.5 to 7.5 and less than 200 ppm of a phosphate, wherein the SAE-CD composition has an absorption of less than 0.5 A.U. due to one or more UV-active drug-degrading agents selected from the group consisting of a glycosidic moiety, a ring-opened cyclodextrin species, a reducing sugar, and a glucose degradation product as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 m of the SAE-CD composition per mL of solution in a cell having a 1 cm path length.

4. A sulfoalkyl ether cyclodextrin (SAE-CD) composition that can be readily mixed with an active agent, comprising a sulfoalkyl ether cyclodextrin having an average degree of substitution of 4.5 to 7.5 and less than 200 ppm of a phosphate, wherein the SAE-CD composition has an absorption of less than 0.5 A.U. due to one or more UV-active drug-degrading agents selected from the group consisting of 3,4-dideoxyglucosone-3-ene, 2-furaldehyde, and 5-hydroxymethyl-2-furaldehyde as determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 300 mg the SAE-CD composition per mL of solution in a cell having a 1 cm path length.

5. A sulfoalkyl ether cyclodextrin (SAE-CD) composition that can be readily mixed with an active agent, comprising a sulfoalkyl ether cyclodextrin having an average degree of substitution of 4.5 to 7.5 and less than 200 ppm of a phosphate, wherein the SAE-CD composition has an absorption of less than 0.5 A.U. due to a UV-active drug-degrading agent formed by exposing a cyclodextrin starting material in an alkaline aqueous media to a substituent precursor at a temperature and for a period of time sufficient to produce the sulfoalkyl ether cyclodextrin 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.

6. A sulfoalkyl ether cyclodextrin (SAE-CD) composition that can be readily mixed with an active agent, comprising a sulfoalkyl ether cyclodextrin having an average degree of substitution of 4.5 to 7.5 and less than 200 ppm of a phosphate, wherein the SAE-CD composition has an absorption of less than 0.5 A.U. due to a UV-active drug-degrading impurity 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, wherein the SAE-CD composition comprises 2% or less of the drug-degrading impurity after the SAE-CD composition is maintained at a temperature of about 80°

C. for a period of about 120 minutes.

7. The SAE-CD composition of claim 6, wherein the SAE-CD composition comprises 0.5% or less of the drug-degrading impurity after the SAE-CD composition is maintained at a temperature of about 80°

C. for a period of about 120 minutes.