As of January 1st, 2019, besides the long valid (August 1st, 2012) monograph in USP NF for Betadex Sulfobutyl Ether Sodium (SBECD, Dexolve, Captisol), EDQM has also accepted and published a monograph in the European Pharmacopeia for the same compound under the name SulfobutylBetadex Sodium (referred version per EP 9.6, final version to be presented in EP 9.8).
The two monographs share several similarities and are equivalent or similar for the majority of the tests included, yet there are also differences in some parameters and test methods that manufacturers and end users should carefully consider. A comparative summary on the two documents is included below, differences highlighted in italic.
0. Definition of the compund is somewhat different according to how the average degree of substitution is measured.
1. ID tests – USP NF has ID tests for retention time with HPLC (assay method) and average degree of substitution with CE, besides the common IR and sodium tests.
2. Assay – same HPLC method and acceptance criterion
3. Heavy metals – harmonized criterion per ICH
4. Limit of beta-cyclodextin – same limit, yet different techniques used
5. Limit of 1,4-butane sultone – same GC method and acceptance criterion
6. Limit of sodium chloride – same limit, yet different technique used
7. Limit of 4-hydroxybutane-1-sulfonic acid – slightly different limit and different technique used
8. Limit of bis(4-sulfobutyl) ether disodium – same limit, yet different technique used
9. Clarity of solution – different sample and acceptance criteria
10. Average degree of substitution – different techniques and acceptance criteria
11. pH – different sample, method and acceptance criteria used
12. Water content – same method and acceptance criterion
13. Reducing sugars – test aimed to detect cyclodextrin related degradation products, only present in EP.
14. Bioburden – harmonized tests, identical limits for TAMC, different limits for TYMC, E. Coli tested in both, Salmonella species tested only per EP.
15. Bacterial endotoxin content – according to general chapters in both
Companies aiming to develop products globally should meet both compendia henceforth.