Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Jun 15:583:119396.
doi: 10.1016/j.ijpharm.2020.119396. Epub 2020 May 4.

Sulfobutylether-β-cyclodextrin

Valentino J Stella  1 , Roger A Rajewski  2
Affiliations
Review

Sulfobutylether-β-cyclodextrin

Valentino J Stella et al. Int J Pharm. .

Abstract

This review presents the early history, the motivation, the research and some of the backstories behind the discovery and development of sulfobutylether-β-cyclodextrin as a novel parenterally safe solubilizer and stabilizer. A specific sulfobutylether-β-cyclodextrin with an average degree of 6.5 sulfobutyl-groups variably substituted on the 2-, 3- and 6-hydroxyls of the seven glucopyranose (dextrose) units of β-cyclodextrin, is known by its commercial name, Captisol®. Today it is in 13 FDA approved injectables and numerous clinical candidates. It is also an example of a novel product discovered and initially preclinically developed at an academic institution.

Keywords: Captisol; Cyclodextrin; Formulation; Safety; Solubility; Stability; Synthesis.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests that could have appeared to influence the work reported in this paper. Professor Stella has consulted for both Gilead and Ligand in the past.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Chemical structure of sulfobutylether-β-cyclodextrin (SBE6.5-β-CD), commercially known as Captisol®, with an average degree of substitution of 6.5.
Fig. 2
Fig. 2
Schematic showing the interaction of a drug molecule with the truncated cone structure of a cyclodextrin to form an inclusion complex.
Fig. 3
Fig. 3
Space filling model structure of β-cyclodextrin (β-CD) and prednisolone, a steroid. Upper left: view down the short axis from the secondary face (2° face) of β-CD. Upper center: a side view of β-CD. Top right: space-filling model of prednisolone, side view. Bottom left: space-filling model of prednisolone along the long-axis showing its fit in the torus of β-CD. Bottom right: the chemical structure of the steroid, prednisolone.
Fig. 4
Fig. 4
General reaction scheme for the synthesis of sulfopropylether-β-cyclodextrins (SPE-β-CDs) and sulfobutylether-β-cyclodextrins (SBE-β-CDs) with varying degrees of substitution (Rajewski, 1990, Stella and Rajewski, 1992, Stella and Rajewski, 1994).
Fig. 5
Fig. 5
Phase solubility diagrams for progesterone in the presence of β-cyclodextrin (β-CD) and various modified β-cyclodextrins (Rajewski, 1990). The modified cyclodextrins include hydroxypropyl-β-cyclodextrin (HP-β-CD); mono-(6-deoxy-sulfonate)- β-cyclodextrin (β-CD mono-6-sulfonate); heptakis-(6-deoxy-sulfonate)- β-cyclodextrin (β-CD poly-6-sulfonate); sulfopropylether-β-cyclodextrin with 1, 3.6 and 7 degrees of substitution (SPEx-β-CD); and sulfobutylether-β-cyclodextrin with 1, 4.7 and 7 degrees of substitution (SBEx-β-CD).
Fig. 6
Fig. 6
Percentage of human red blood hemolysis in the presence of β-cyclodextrin (β-CD) and various modified β-cyclodextrins (Rajewski, 1990). The modified cyclodextrins include hydroxypropyl-β-cyclodextrin (HP-β-CD); mono-(6-deoxy-sulfonate)- β-cyclodextrin (β-CD mono-6-sulfonate); heptakis-(6-deoxy-sulfonate)-β-cyclodextrin (β-CD poly-6-sulfonate); sulfopropylether-β-cyclodextrin with 1, 3.6 and 7 degrees of substitution (SPEx-β-CD); and sulfobutylether-β-cyclodextrin with 1, 4.7 and 7 degrees of substitution (SBEx-β-CD).
See this image and copyright information in PMC

References

    1. Dye D., Watkins J. Suspected anaphylactic reaction to Cremophor EL. Brit. Med. J. 1980;280(6228):1353. - PMC - PubMed
    1. Frank D.W., Gray J.E., Weaver R.N. Cyclodextrin nephrosis in the rat. Am. J. Path. 1976;83(2):367. - PMC - PubMed
    1. Hüttel M.S., Schou Olesen A., Stoffersen S. Complement-mediated reactions to diazepam with Cremophor as solvent (Stesolid MR) Brit. J. Anaesth. 1980;52(1):77–79. - PubMed
    1. Luke D.R., Tomaszewski K., Damle B., Schlamm H.T. Review of the basic and clinical pharmacology of sulfobutylether-β-cydodextrin (SBECD) J. Pharm. Sci. 2010;99(8):3291–3301. - PubMed
    1. Müller B.W., Brauns U. Change of phase-solubility behavior by gamma-cyclodextrin derivatization. Pharm Res. 1985;2(6):309–310. - PubMed