Alkylated cyclodextrin compositions and processes for preparing and using the same
The present invention related to low-chloride alkylated cyclodextrin compositions, along with processes for preparing and using the same. The processes of the present invention provide alkylated cyclodextrins with low levels of drug-degrading agents and chloride.
1. A process for preparing an alkylated cyclodextrin composition comprising an alkylated cyclodextrin, the process comprising:
(a) mixing a cyclodextrin with an alkylating agent to form a reaction milieu comprising an alkylated cyclodextrin, one or more unwanted components, and one or more drug-degrading impurities;
(b) conducting one or more separations to remove the one or more unwanted components from the reaction milieu to form a partially purified solution comprising the alkylated cyclodextrin and the one or more drug-degrading impurities, wherein the one or more separations are ultrafiltration, diafiltration, centrifugation, extraction, solvent precipitation, or dialysis;
(c) conducting two or more treatments of the partially purified solution with a phosphate-free activated carbon having a residual conductivity of 10 μS or less and producing the alkylated cyclodextrin; wherein the two or more treatments of step (c) are each conducted for at least 2 hours.
2. The process of claim 1 , wherein the phosphate-free activated carbon of step (c) is a granular activated carbon.
3. The process of claim 1 , wherein the cyclodextrin of step (a) is β-cyclodextrin and the alkylating agent of step (a) is butane sultone.
4. The process of claim 1 , wherein the alkylated cyclodextrin composition further does not comprise 400 ppm or more of a phosphate.
5. The process of claim 1 , wherein the alkylated cyclodextrin composition further does not comprise 300 ppm or more of a phosphate.
6. The process of claim 1 , wherein the alkylated cyclodextrin composition further does not comprise 200 ppm or more of a phosphate.
7. The process of claim 1 , wherein the alkylated cyclodextrin composition further does not comprise 125 ppm or more of a phosphate.
8. The process of claim 1 , wherein the residual conductivity in (c) is 9 μS or less.
9. The process of claim 1 , wherein the residual conductivity in (c) is 8 μS or less.
10. The process of claim 1 , wherein the alkylated cyclodextrin composition further does not comprise 0.5% (w/w) or more of a chloride.
11. The process of claim 1 , wherein the alkylated cyclodextrin composition further does not comprise more than 0.1% (w/w) of a chloride.
12. The process of claim 1 , wherein the alkylated cyclodextrin composition further does not comprise more than 0.07% (w/w) of a chloride.
13. The process of claim 1 , wherein the alkylated cyclodextrin composition further does not comprise more than 0.05% (w/w) of a chloride.
14. The process of claim 1 , wherein the alkylated cyclodextrin composition has no detectable levels of a chloride as determined by charged aerosol detection.
15. The process of claim 1 , wherein the alkylated cyclodextrin composition has an average degree of substitution of 2 to 9.
16. The process of claim 1 , wherein the alkylated cyclodextrin composition has an average degree of substitution of 4.5 to 7.5.
17. The process of claim 1 , wherein the alkylated cyclodextrin composition has an average degree of substitution of 6 to 7.5.
18. The process of claim 1 , wherein the alkylated cyclodextrin composition has an absorption of less than 1 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 alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
19. The process of claim 1 , wherein the alkylated cyclodextrin 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 300 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
20. The process of claim 19 , wherein the absorption is due to a drug degrading agent.
21. The process of claim 20 , wherein the absorption is determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
22. The process of claim 1 , wherein the alkylated cyclodextrin composition has an absorption of less than 1 A.U., as determined by UV/vis spectrophotometry at a wavelength of 320 nm to 350 nm for an aqueous solution containing 300 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
23. The process of claim 1 , wherein the alkylated cyclodextrin composition has an absorption of less than 0.5 A.U., as determined by UV/vis spectrophotometry at a wavelength of 320 nm to 350 nm for an aqueous solution containing 300 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
24. The process of claim 23 , wherein the absorption is due to a color forming agent.
25. The process of claim 24 , wherein the absorption is determined by UV/vis spectrophotometry at a wavelength of 320 nm to 350 nm for an aqueous solution containing 500 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
26. The process of claim 1 , wherein the phosphate-free activated carbon is washed with a solvent until the eluted solvent has reached the residual conductivity in (c).
27. The process of claim 1 , wherein the phosphate-free activated carbon is washed with water until the eluted water has reached the residual conductivity in (c).
28. The process of claim 1 , further comprising:
(d) treating the alkylated cyclodextrin of step (c) with a method selected from the group consisting of lyophilization, spray-drying, spray freeze-drying, antisolvent precipitation, and aseptic spray drying, whereby a reconstitutable solid composition is formed.
29. The process of claim 1 , 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.
30. The process of claim 29 , 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.
31. The process of claim 29 , wherein the sulfoalkyl ether cyclodextrin is sulfobutyl ether β-cyclodextrin having an average degree of substitution of 6.0 to 7.1.
32. The process of claim 1 , further comprising combining the alkylated cyclodextrin composition with one or more excipients.
33. The process of claim 1 , further comprising combining the alkylated cyclodextrin composition with an active agent.
34. The process of claim 33 , wherein the active agent is a chloride sensitive active agent selected from the group consisting of bortezomib, disulfiram, epigallocatchin-3-gallate, salinosporamide A, and carfilzomib.
35. The process of claim 34 wherein the chloride sensitive active agent is carfilzomib.
36. A process for preparing an alkylated cyclodextrin composition comprising an alkylated cyclodextrin, the process comprising:
(a) mixing a cyclodextrin with an alkylating agent to form a reaction milieu comprising an alkylated cyclodextrin, one or more unwanted components, and one or more drug-degrading impurities;
(b) conducting one or more separations to remove the one or more unwanted components from the reaction milieu to form a partially purified solution comprising the alkylated cyclodextrin and the one or more drug-degrading impurities, wherein the one or more separations are ultrafiltration, diafiltration, centrifugation, extraction, solvent precipitation, or dialysis;
(c) conducting two or more treatments of the partially purified solution with a phosphate-free activated carbon having a residual conductivity of 10 μS or less and producing the alkylated cyclodextrin;
wherein the phosphate-free activated carbon of step (c) is a granular activated carbon.
37. The process of claim 36 , wherein the two or more treatments of step (c) are each conducted for at least 2 hours.
38. The process of claim 36 , wherein the cyclodextrin of step (a) is β-cyclodextrin and the alkylating agent of step (a) is butane sultone.
39. The process of claim 36 , wherein the alkylated cyclodextrin composition further does not comprise 400 ppm or more of a phosphate.
40. The process of claim 36 , wherein the alkylated cyclodextrin composition further does not comprise 300 ppm or more of a phosphate.
41. The process of claim 36 , wherein the alkylated cyclodextrin composition further does not comprise 200 ppm or more of a phosphate.
42. The process of claim 36 , wherein the alkylated cyclodextrin composition further does not comprise than 125 ppm of a phosphate.
43. The process of claim 36 , wherein the residual conductivity in (c) is 9 μS or less.
44. The process of claim 36 , wherein the residual conductivity in (c) is 8 μS or less.
45. The process of claim 36 , wherein the alkylated cyclodextrin composition further does not comprise 0.5% (w/w) or more of a chloride.
46. The process of claim 36 , wherein the alkylated cyclodextrin composition further does not comprise more than 0.1% (w/w) of a chloride.
47. The process of claim 36 , wherein the alkylated cyclodextrin composition further does not comprise more than 0.07% (w/w) of a chloride.
48. The process of claim 36 , wherein the alkylated cyclodextrin composition further does not comprise more than 0.05% (w/w) of a chloride.
49. The process of claim 36 , wherein the alkylated cyclodextrin composition has no detectable levels of a chloride as determined by charged aerosol detection.
50. The process of claim 36 , wherein the alkylated cyclodextrin composition has an average degree of substitution of 2 to 9.
51. The process of claim 36 , wherein the alkylated cyclodextrin composition has an average degree of substitution of 4.5 to 7.5.
52. The process of claim 36 , wherein the alkylated cyclodextrin composition has an average degree of substitution of 6 to 7.5.
53. The process of claim 36 , wherein the alkylated cyclodextrin composition has an absorption of less than 1 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 alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
54. The process of claim 36 , wherein the alkylated cyclodextrin 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 300 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
55. The process of claim 54 , wherein the absorption is due to a drug degrading agent.
56. The process of claim 55 , wherein the absorption is determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
57. The process of claim 36 , wherein the alkylated cyclodextrin composition has an absorption of less than 1 A.U., as determined by UV/vis spectrophotometry at a wavelength of 320 nm to 350 nm for an aqueous solution containing 300 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
58. The process of claim 36 , wherein the alkylated cyclodextrin composition has an absorption of less than 0.5 A.U., as determined by UV/vis spectrophotometry at a wavelength of 320 nm to 350 nm for an aqueous solution containing 300 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
59. The process of claim 58 , wherein the absorption is due to a color forming agent.
60. The process of claim 59 , wherein the absorption is determined by UV/vis spectrophotometry at a wavelength of 320 nm to 350 nm for an aqueous solution containing 500 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
61. The process of claim 36 , wherein the phosphate-free activated carbon is washed with a solvent until the eluted solvent has reached the residual conductivity in (c).
62. The process of claim 36 , wherein the phosphate-free activated carbon is washed with water until the eluted water has reached the residual conductivity in (c).
63. The process of claim 36 , further comprising:
(d) treating the alkylated cyclodextrin of step (c) with a method selected from the group consisting of lyophilization, spray-drying, spray freeze-drying, antisolvent precipitation, and aseptic spray drying, whereby a reconstitutable solid composition is formed.
64. The process of claim 36 , 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.
65. The process of claim 64 , 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.
66. The process of claim 64 , wherein the sulfoalkyl ether cyclodextrin is sulfobutyl ether β-cyclodextrin having an average degree of substitution of 6.0 to 7.1.
67. The process of claim 36 , further comprising combining the alkylated cyclodextrin composition with one or more excipients.
68. The process of claim 36 , further comprising combining the alkylated cyclodextrin composition with an active agent.
69. The process of claim 68 , wherein the active agent is a chloride sensitive active agent selected from the group consisting of bortezomib, disulfiram, epigallocatchin-3-gallate, salinosporamide A, and carfilzomib.
70. The process of claim 69 wherein the chloride sensitive active agent is carfilzomib.
71. A process for preparing an alkylated cyclodextrin composition comprising an alkylated cyclodextrin, the process comprising:
(a) mixing a cyclodextrin with an alkylating agent to form a reaction milieu comprising an alkylated cyclodextrin, one or more unwanted components, and one or more drug-degrading impurities, wherein the cyclodextrin of step (a) is β-cyclodextrin and the alkylating agent of step (a) is butane sultone;
(b) conducting one or more separations to remove the one or more unwanted components from the reaction milieu to form a partially purified solution comprising the alkylated cyclodextrin and the one or more drug-degrading impurities, wherein the one or more separations are ultrafiltration, diafiltration, centrifugation, extraction, solvent precipitation, or dialysis; and
(c) conducting two or more treatments of the partially purified solution with a phosphate-free activated carbon having a residual conductivity of 10 μS or less and producing the alkylated cyclodextrin.
72. The process of claim 71 , wherein the phosphate-free activated carbon of step (c) is a granular activated carbon.
73. The process of claim 71 , wherein the two or more treatments of step (c) are each conducted for at least 2 hours.
74. The process of claim 71 , wherein the alkylated cyclodextrin composition further does not comprise 400 ppm or more of a phosphate.
75. The process of claim 71 , wherein the alkylated cyclodextrin composition further does not comprise 300 ppm or more of a phosphate.
76. The process of claim 71 , wherein the alkylated cyclodextrin composition further does not comprise 200 ppm or more of a phosphate.
77. The process of claim 71 , wherein the alkylated cyclodextrin composition further does not comprise 125 ppm or more of a phosphate.
78. The process of claim 71 , wherein the residual conductivity in (c) is 9 μS or less.
79. The process of claim 71 , wherein the residual conductivity in (c) is 8 μS or less.
80. The process of claim 71 , wherein the alkylated cyclodextrin composition further does not comprise 0.5% (w/w) or more of a chloride.
81. The process of claim 71 , wherein the alkylated cyclodextrin composition further does not comprise more than 0.1% (w/w) of a chloride.
82. The process of claim 71 , wherein the alkylated cyclodextrin composition further does not comprise more than 0.07% (w/w) of a chloride.
83. The process of claim 71 , wherein the alkylated cyclodextrin composition further does not comprise more than 0.05% (w/w) of a chloride.
84. The process of claim 71 , wherein the alkylated cyclodextrin composition has no detectable levels of a chloride as determined by charged aerosol detection.
85. The process of claim 71 , wherein the alkylated cyclodextrin composition has an average degree of substitution of 2 to 9.
86. The process of claim 71 , wherein the alkylated cyclodextrin composition has an average degree of substitution of 4.5 to 7.5.
87. The process of claim 71 , wherein the alkylated cyclodextrin composition has an average degree of substitution of 6 to 7.5.
88. The process of claim 71 , wherein the alkylated cyclodextrin composition has an absorption of less than 1 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 alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
89. The process of claim 71 , wherein the alkylated cyclodextrin 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 300 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
90. The process of claim 89 , wherein the absorption is due to a drug degrading agent.
91. The process of claim 90 , wherein the absorption is determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
92. The process of claim 71 , wherein the alkylated cyclodextrin composition has an absorption of less than 1 A.U., as determined by UV/vis spectrophotometry at a wavelength of 320 nm to 350 nm for an aqueous solution containing 300 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
93. The process of claim 71 , wherein the alkylated cyclodextrin composition has an absorption of less than 0.5 A.U., as determined by UV/vis spectrophotometry at a wavelength of 320 nm to 350 nm for an aqueous solution containing 300 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
94. The process of claim 93 , wherein the absorption is due to a color forming agent.
95. The process of claim 94 , wherein the absorption is determined by UV/vis spectrophotometry at a wavelength of 320 nm to 350 nm for an aqueous solution containing 500 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
96. The process of claim 71 , wherein the phosphate-free activated carbon is washed with a solvent until the eluted solvent has reached the residual conductivity in (c).
97. The process of claim 71 , wherein the phosphate-free activated carbon is washed with water until the eluted water has reached the residual conductivity in (c).
98. The process of claim 71 , further comprising:
(d) treating the alkylated cyclodextrin of step (c) with a method selected from the group consisting of lyophilization, spray-drying, spray freeze-drying, antisolvent precipitation, and aseptic spray drying, whereby a reconstitutable solid composition is formed.
99. The process of claim 71 , 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.
100. The process of claim 99 , 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.
101. The process of claim 99 , wherein the sulfoalkyl ether cyclodextrin is sulfobutyl ether β-cyclodextrin having an average degree of substitution of 6.0 to 7.1.
102. The process of claim 71 , further comprising combining the alkylated cyclodextrin composition with one or more excipients.
103. The process of claim 71 , further comprising combining the alkylated cyclodextrin composition with an active agent.
104. The process of claim 103 , wherein the active agent is a chloride sensitive active agent selected from the group consisting of bortezomib, disulfiram, epigallocatchin-3-gallate, salinosporamide A, and carfilzomib.
105. The process of claim 104 wherein the chloride sensitive active agent is carfilzomib.
106. A process for preparing an alkylated cyclodextrin composition comprising an alkylated cyclodextrin, the process comprising:
(a) mixing a cyclodextrin with an alkylating agent to form a reaction milieu comprising an alkylated cyclodextrin, one or more unwanted components, and one or more drug-degrading impurities;
(b) conducting one or more separations to remove the one or more unwanted components from the reaction milieu to form a partially purified solution comprising the alkylated cyclodextrin and the one or more drug-degrading impurities, wherein the one or more separations are ultrafiltration, diafiltration, centrifugation, extraction, solvent precipitation, or dialysis;
(c) conducting two or more treatments of the partially purified solution with a phosphate-free activated carbon having a residual conductivity of 10 μS or less and producing the alkylated cyclodextrin; and
(d) treating the alkylated cyclodextrin of step (c) with a method selected from the group consisting of lyophilization, spray-drying, spray freeze-drying, antisolvent precipitation, and aseptic spray drying, whereby a reconstitutable solid composition is formed.
107. The process of claim 106 , wherein the phosphate-free activated carbon of step (c) is a granular activated carbon.
108. The process of claim 106 , wherein the two or more treatments of step (c) are each conducted for at least 2 hours.
109. The process of claim 106 , wherein the alkylated cyclodextrin composition further does not comprise 400 ppm or more of a phosphate.
110. The process of claim 106 , wherein the alkylated cyclodextrin composition further does not comprise than 300 ppm or more of a phosphate.
111. The process of claim 106 , wherein the alkylated cyclodextrin composition further does not comprise 200 ppm or more of a phosphate.
112. The process of claim 106 , wherein the alkylated cyclodextrin composition further does not comprise 125 ppm of a phosphate.
113. The process of claim 106 , wherein the residual conductivity in (c) is 9 μS or less.
114. The process of claim 106 , wherein the residual conductivity in (c) is 8 μS or less.
115. The process of claim 106 , wherein the alkylated cyclodextrin composition further does not comprise 0.5% (w/w) or more of a chloride.
116. The process of claim 106 , wherein the alkylated cyclodextrin composition further does not comprise more than 0.1% (w/w) of a chloride.
117. The process of claim 106 , wherein the alkylated cyclodextrin composition further does not comprise more than 0.07% (w/w) of a chloride.
118. The process of claim 106 , wherein the alkylated cyclodextrin composition further does not comprise more than 0.05% (w/w) of a chloride.
119. The process of claim 106 , wherein the alkylated cyclodextrin composition has no detectable levels of a chloride as determined by charged aerosol detection.
120. The process of claim 106 , wherein the alkylated cyclodextrin composition has an average degree of substitution of 2 to 9.
121. The process of claim 106 , wherein the alkylated cyclodextrin composition has an average degree of substitution of 4.5 to 7.5.
122. The process of claim 106 , wherein the alkylated cyclodextrin composition has an average degree of substitution of 6 to 7.5.
123. The process of claim 106 , wherein the alkylated cyclodextrin composition has an absorption of less than 1 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 alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
124. The process of claim 106 , wherein the alkylated cyclodextrin 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 300 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
125. The process of claim 124 , wherein the absorption is due to a drug degrading agent.
126. The process of claim 125 , wherein the absorption is determined by UV/vis spectrophotometry at a wavelength of 245 nm to 270 nm for an aqueous solution containing 500 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
127. The process of claim 106 , wherein the alkylated cyclodextrin composition has an absorption of less than 1 A.U., as determined by UV/vis spectrophotometry at a wavelength of 320 nm to 350 nm for an aqueous solution containing 300 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
128. The process of claim 106 , wherein the alkylated cyclodextrin composition has an absorption of less than 0.5 A.U., as determined by UV/vis spectrophotometry at a wavelength of 320 nm to 350 nm for an aqueous solution containing 300 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
129. The process of claim 128 , wherein the absorption is due to a color forming agent.
130. The process of claim 129 , wherein the absorption is determined by UV/vis spectrophotometry at a wavelength of 320 nm to 350 nm for an aqueous solution containing 500 mg of the alkylated cyclodextrin composition per mL of solution in a cell having a 1 cm path length.
131. The process of claim 106 , wherein the phosphate-free activated carbon is washed with a solvent until the eluted solvent has reached the residual conductivity in (c).
132. The process of claim 106 , wherein the phosphate-free activated carbon is washed with water until the eluted water has reached the residual conductivity in (c).
133. The process of claim 106 , wherein the alkylated cyclodextrin is a sulfoalkyl ether cyclodextrin of Formula (II):
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.
134. The process of claim 133 , 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.
135. The process of claim 133 , wherein the sulfoalkyl ether cyclodextrin is sulfobutyl ether β-cyclodextrin having an average degree of substitution of 6.0 to 7.1.
136. The process of claim 106 , further comprising combining the alkylated cyclodextrin composition with one or more excipients.
137. The process of claim 106 , further comprising combining the alkylated cyclodextrin composition with an active agent.
138. The process of claim 137 , wherein the active agent is a chloride sensitive active agent selected from the group consisting of bortezomib, disulfiram, epigallocatchin-3-gallate, salinosporamide A, and carfilzomib.
139. The process of claim 138 , wherein the chloride sensitive active agent is carfilzomib.