Sulfoalkyl ether cyclodextrin compositions and methods of preparation thereof

1. A method of preparing a pharmaceutical composition comprising a sulfoalkyl ether cyclodextrin and an active agent, the method comprising

combining a sulfoalkyl ether cyclodextrin starting composition, the active agent, and a liquid carrier to form a solution, and wherein the sulfoalkyl ether cyclodextrin starting composition comprises agglomerated particles and has

a bulk density in the range of about 0.38 g/cm 3 to about 0.66 g/cm 3 ; and

a tapped density in the range of about 0.49 g/cm 3 to about 0.75 g/cm 3 .

2. The method of claim 1 , wherein the tapped density is in the range of 0.66 g/cm 3 to about 0.75 g/cm 3 .

3. The method of claim 1 , wherein the bulk density is in the range of 0.55 g/cm 3 to about 0.66 g/cm 3 .

4. The method of claim 1 , wherein the sulfoalkyl ether cyclodextrin is mixed with the liquid carrier prior to addition of the active agent.

5. The method of claim 1 , wherein the sulfoalkyl ether cyclodextrin is mixed with the liquid carrier during addition of the active agent.

6. The method of claim 1 , wherein the sulfoalkyl ether cyclodextrin is mixed with the liquid carrier after addition of the active agent.

7. A composition comprising an excipient and a sulfoalkyl ether cyclodextrin composition, wherein the sulfoalkyl ether cyclodextrin composition has:

(a) no more than about 20% by weight moisture;

(b) a bulk density of about 0.38 g/cm 3 to about 0.66 g/cm 3 ;

(c) a tapped density of about 0.49 g/cm 3 to about 0.75 g/cm 3 , wherein the tapped density of the sulfoalkyl ether cyclodextrin composition is higher than the bulk density; and

(d) a gravitational-flow minimum orifice diameter of about 3 mm to about 12 mm; and

wherein the sulfoalkyl ether cyclodextrin composition comprises agglomerated particles.

8. The composition of claim 6 , wherein the sulfoalkyl ether cyclodextrin is a compound, or a mixture of compounds, of the Formula 1:

wherein:

n is 4, 5, or 6;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are each, independently, O − or a O—(C 2-6 alkylene)-SO 3 − group, wherein at least one of R 1 and R 2 is, independently, the O—(C 2 -C 6 alkylene)-SO 3 − group; and

S 1 , S 2 , S 3 , S 4 , S 5 , S 6 , S 7 , S 8 , and S 9 , are each, independently, a pharmaceutically acceptable cation.

9. The composition of claim 6 , wherein the sulfoalkyl ether cyclodextrin composition has a bulk density of about 0.38 g/cm 3 to about 0.55 g/cm 3 and a tapped density of about0.49 g/cm 3 to about 0.66 g/cm 3 .

10. The composition of claim 6 , wherein the sulfoalkyl ether cyclodextrin composition has a gravitational-flow minimum orifice diameter of about 3 mm to about 7 mm.

11. The composition of claim 7 , wherein the sulfoalkyl ether cyclodextrin composition has a CARR's index of about 18% or less.

12. The composition of claim 7 , wherein the sulfoalkyl ether cyclodextrin composition has a CARR's index of about 24% or less.

13. The composition of claim 7 , wherein the sulfoalkyl ether cyclodextrin composition comprises particles with a mean particle diameter of about 75 microns to about 200 microns.

14. The composition of claim 7 , wherein 2.5 g of the sulfoalkyl ether cyclodextrin composition has an average dissolution time of about 2 min to about 4.5 min when placed in water.

15. A sulfoalkyl ether cyclodextrin composition comprising sulfoalkyl ether cyclodextrin (SAE-CD) wherein the composition comprises agglomerated particles and has:

(a) a gravitational-flow minimum orifice diameter of less than about 20 mm;

(b) an average dissolution time of 4.5 minutes or less when 2.5 g of the composition is placed in water; and

(c) a compression crushing strength in the range of about 1.0 kP to about 20 kP when 200 mg of the composition is compressed into a tablet having a diameter of 0.345inches using a Pmax in the range of about 30 MPa to about 275 MPa and when the composition has a moisture content in the range of about 2% to about 3% by weight, or a compression crushing strength in the range of about 0.5 kP to about 11 kP when 200 mg of the composition is compressed into a tablet having a diameter of 0.345 inches using a Pmax in the range of about 15 MPa to about 70 MPa and when the composition has a moisture content in the range of about 5% to about 6% by weight.

16. The SAE-CD composition of claim 15 , wherein the composition comprises a moisture content of less than 18% by weight.

17. The SAE-CD composition of claim 15 , wherein the composition has a bulk density of about 0.38 g/cm 3 to about 0.66 g/cm 3 and a tapped density of about 0.49 g/cm 3 to about 0.75 g/cm 3 .

18. The SAE-CD composition of claim 15 , wherein the agglomerated particles have a mean particle diameter of 92 to 200 μm.

19. The SAE-CD composition of claim 15 , wherein the composition has a CARR's index of about 24% or less.

20. The SAE-CD composition of claim 15 , wherein the composition has a CARR's index of about 18% or less.

21. The SAE-CD composition of claim 15 , wherein the gravitational-flow minimum orifice diameter of the composition is 10 mm or less.

22. The SAE-CD composition of claim 15 , wherein the gravitational-flow minimum orifice diameter of the composition is in the range of about 3 mm to 7 mm.

23. The SAE-CD composition of claim 15 , wherein the gravitational-flow minimum orifice diameter of the composition is in the range of about 3 mm to 12 mm.

24. The SAE-CD composition of claim 15 , wherein the average dissolution time of the composition is in the range of about 2.5 min to about 4.5 min when 2.5 g of the composition is placed in water.

25. The SAE-CD composition of claim 15 , wherein the bulk density is in the range of 0.55 g/cm 3 to 0.66 g/cm 3 and the tapped density is in the range of about 0.66 g/cm 3 to 0.75 g/cm 3 .