Compositions of hydroxypropyl-β-cyclodextrin and methods of purifying the same
The present disclosure relates to compositions comprising mixtures of hydroxypropyl-β-cyclodextrin, wherein the compositions may be isomerically purified. The disclosure also relates to methods of isomerically purifying a mixture of hydroxypropyl-β-cyclodextrins.
1. A composition comprising a mixture of isomerically-purified hydroxypropyl β-cyclodextrin molecules comprising: β-cyclodextrin substituted with seven hydroxypropyl groups (“DS-7”); wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with five hydroxypropyl groups (“DS-5”), and wherein the mixture has an average degree of substitution of 6.02-7.98, and wherein the total amount of impurities are measured to be less than or equal to 0.05% by HPLC.
2. The composition of claim 1 , wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with four hydroxypropyl groups (“DS-4”).
3. The composition of claim 1 , wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with three hydroxypropyl groups (“DS-3”).
4. The composition of claim 1 , wherein the mixture further comprises less than 0.05% by mass unsubstituted beta-cyclodextrin (“DS-0”) and less than 0.05% by mass β-cyclodextrin substituted with one hydroxypropyl group (“DS-1”).
5. The composition of claim 1 , wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with eight hydroxypropyl groups (“DS-8”).
6. The composition of claim 1 , wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with nine hydroxypropyl groups (“DS-9”).
7. The composition of claim 1 , wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with ten hydroxypropyl groups (“DS-10”).
8. The composition of claim 1 , wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with eleven hydroxypropyl groups (“DS-11”).
9. The composition of claim 1 , wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with twelve hydroxypropyl groups (“DS-12”).
10. The composition of claim 1 , wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with thirteen hydroxypropyl groups (“DS-13”).
11. The composition of claim 1 , wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with fourteen hydroxypropyl groups (“DS-14”).
12. The mixture of claim 1 , wherein the composition has an HPLC-CAD mean retention time of about 10.1 minutes.
13. The composition of claim 1 , wherein the osmolality of the composition is about 635-695 mOs/kg; and/or wherein the true density of the composition is about 1.096-1.098 g/cm 3 .
14. The composition of claim 1 , wherein the composition further comprises no more than 10 ppb of propylene glycol as measured by HPLC.
15. The composition of claim 1 , wherein the composition further comprises no more than 10 ppb propylene glycol as measured by gas chromatography.
16. The composition of claim 1 , wherein the composition further comprises no more than 10 ppb propylene glycol as measured by PG/EG-ratio of propylene glycol to ethylene glycol.
17. The composition of claim 1 , wherein the composition further comprises no more than 1 ppm propylene oxide.
18. The composition of claim 1 , wherein the composition further comprises between 0 and 10 ppm chloride.
19. The composition of claim 1 , wherein the composition has a conductivity between 0 and 8 μS/cm.
20. A composition comprising a mixture of isomerically-purified hydroxypropyl β-cyclodextrin molecules comprising: β-cyclodextrin substituted with seven hydroxypropyl groups (“DS-7”); wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with four hydroxypropyl groups (“DS-4”), and wherein the composition has an average degree of substitution of 6.02-7.98, and wherein the total amount of impurities are measured to be less than or equal to 0.05% by HPLC.
21. The mixture further of claim 20 , wherein the composition comprises less than 1% by mass β-cyclodextrin substituted with three hydroxypropyl groups (“DS-3”).
22. The composition of claim 20 , wherein the mixture further comprises less than 0.05% by mass unsubstituted beta-cyclodextrin (“DS-0”) and less than 0.05% by mass β-cyclodextrin substituted with one hydroxypropyl group (“DS-1”).
23. A composition comprising a mixture of isomerically-purified hydroxypropyl β-cyclodextrin molecules comprising: β-cyclodextrin substituted with seven hydroxypropyl groups (“DS-7”); wherein the mixture further comprises less than 1% by mass β-cyclodextrin substituted with five hydroxypropyl groups (“DS-5”), and wherein the mixture has an average degree of substitution of 6.02-7.98 and the mixture is determined by MALDI-TOF mass spectrometry.
24. The composition of claim 23 , wherein the percentage of DS-5 is determined by MALDI-TOF mass spectrometry.
25. The composition of claim 23 , wherein the composition is suitable for administration to a human patient in need thereof.
26. A composition comprising a mixture of isomerically-purified hydroxypropyl β-cyclodextrin molecules comprising: β-cyclodextrin substituted with seven hydroxypropyl groups (“DS-7”); wherein the mixture further less than 1% by mass β-cyclodextrin substituted with four hydroxypropyl groups (“DS-4”), and wherein the mixture has an average degree of substitution of 6.02-7.98 and the mixture is determined by MALDI-TOF mass spectrometry.
27. The composition of claim 26 , wherein the percentage of DS-4 is determined by MALDI-TOF mass spectrometry.
28. The composition of claim 26 , wherein the composition is suitable for administration to a human patient in need thereof.