Hydroxypropyl beta-cyclodextrin compositions and methods
This disclosure provides mixtures of beta-cyclodextrin molecules substituted at one or more hydroxyl positions by hydroxypropyl groups, the mixture optionally including unsubstituted beta-cyclodextrin molecules, for use as a pharmaceutically active ingredient; methods of making such mixtures; methods of qualifying such mixtures for use in a pharmaceutical composition suitable for intrathecal or intracerebroventricular administration; pharmaceutical compositions suitable for intrathecal or intracerebroventricular administration comprising such mixtures; and methods of using the pharmaceutical compositions for treatment of Niemann-Pick disease Type C.
1. A composition for intravenous injection comprising a mixture of beta-cyclodextrin molecules substituted at one or more hydroxyl positions by hydroxypropyl groups, wherein the composition is pharmaceutically acceptable for intravenous administration and the composition comprises less than 2 International Units (IU) of endotoxins per gram.
2. The composition of claim 1 , wherein the composition comprises no more than 0.5% propylene glycol.
3. The composition of claim 1 , wherein the composition comprises no more than 1 ppm propylene oxide.
4. The composition of claim 1 , wherein the composition comprises less than 1.5 IU of endotoxins per gram.
5. The composition of claim 1 , wherein the composition comprises less than 1.2 IU of endotoxins per gram.
6. The composition of claim 1 , wherein the composition comprises less than 1 IU of endotoxins per gram.
7. The composition of claim 1 , wherein the composition comprises sodium chloride to 0.9% w/v.
8. The composition of claim 1 , wherein the composition comprises a pH of 6.0-8.0.
9. The composition of claim 1 , wherein the composition is sterile filtered.
10. The composition of claim 1 , wherein the composition can be stored at 15-25° C.
11. The composition of claim 1 , wherein the mixture comprises less than 3.5% collectively of unsubstituted beta-cyclodextrin (“DS-0”), beta-cyclodextrin substituted with one hydroxypropyl group (“DS-1”), and beta-cyclodextrin substituted with two hydroxypropyl groups (“DS-2”).
12. The composition of claim 1 , wherein the mixture comprises less than 1.0% collectively of unsubstituted beta-cyclodextrin (“DS-0”), beta-cyclodextrin substituted with one hydroxypropyl group (“DS-1”).
13. The composition of claim 11 , wherein the mixture comprises less than 1.0% beta-cyclodextrin substituted with one hydroxypropyl group (“DS-1”).
14. The composition of claim 11 , wherein the mixture comprises less than 0.5% beta-cyclodextrin substituted with one hydroxypropyl group (“DS-1”).
15. The composition of claim 11 , wherein the mixture comprises less than 0.03% beta-cyclodextrin substituted with one hydroxypropyl group (“DS-1”).
16. The composition of claim 11 , wherein the mixture comprises less than 1.0% beta-cyclodextrin substituted with two hydroxypropyl groups (“DS-2”).
17. The composition of claim 11 , wherein the mixture comprises less than 0.5% beta-cyclodextrin substituted with two hydroxypropyl groups (“DS-2”).
18. The composition of claim 11 , wherein the mixture comprises less than 0.03% beta-cyclodextrin substituted with two hydroxypropyl groups (“DS-2”).
19. The composition of claim 1 , wherein less than 0.1% of the beta-cyclodextrin mixture is DS-0 and DS-1, collectively.
20. The composition of claim 1 , wherein less than 0.01% of the beta-cyclodextrin mixture is DS-0 and DS-1, collectively.
21. The composition of claim 1 , wherein the mixture composition has an osmolality of about 300 to about 450 mOsm/kg.
22. The composition of claim 1 , wherein the mixture has an average degree of substitution (“DS a ”) of about 3 to about 7.
23. The composition of claim 1 , wherein the total amount of other unspecified impurities is less than or equal to 0.05% as measured by HPLC.
24. The composition of claim 1 , wherein the composition has a concentration of about 10 mg/ml to about 200 mg/mL.
25. The composition of claim 1 , wherein the wherein the composition is suitable for administration to a pediatric patient.
26. The composition of claim 1 , wherein the wherein the composition is suitable for administration to an adult patient.
27. The composition of claim 1 , further comprising a pharmaceutically acceptable diluent.