Sulfobutylether β- Cyclodextrin

Category

Biocompatibility enhancer; Osmotic Agents; Solubilizing Agents; Stabilizing Agents; Tablet and Capsule Diluent; Viscosity-increasing Agents; Water activity reducing Agents

Molecular Formula

C42H70-nO35·(C4H8SO3Na)n

Molecular Weight

2163 (where n = approximately 6.5)

Grade

Pharmceutical Excipients

Description

β-Cyclodextrin is a cyclic oligosaccharide containing seven D-(+)-glucopyranose units attached by a(1→4) glucoside bonds. Sulfobutylether b-cyclodextrin is an anionic β-cyclodextrin derivative with a sodium sulfonate salt separated from the hydrophobic cavity by a butyl spacer group. The substituent is introduced at positions 2, 3, and 6 in at least one of the glucopyranose units in the cyclodextrin structure.

UNII

NA

Chemical Name

β-Cyclodextrin sulfobutylether, sodium salt

CAS Number

1824100-00-0

Synonyms

β-Cyclodextrin sulfobutylether, sodium salt; Captisol; (SBE)m-betaCD; SBE7-b-CD; SBECD; sulfobutylether-β-cyclodextrin, sodium salt

Administration route

SC, oral, inhalation, nasal and ophthalmic, IV and IM

Dosage Form

SC, oral, inhalation, nasal and ophthalmic, IV and IM injectable products

Stability and Storage Conditions

Sulfobutylether β-cyclodextrin is stable in the solid state and should be protected from high humidity. It should be stored in a tightly sealed container in a cool, dry place. It will reversibly take up moisture without any effect on the appearance of the material at humidities up to 60% RH.Equilibration at RH values above 60% will result in deliquescence.Once in this state, the material can be dried, but will give a glasslike product. This water absorption behavior is typical of amorphous hygroscopic materials. Sulfobutylether β-cyclodextrin is stable in aqueous solutions at values above about pH 1. It can degrade in highly acidic (pH < 1) solutions, particularly at elevated temperatures, producing the ring opened form, followed by hydrolysis of the a(1→4) glucoside bonds. Sulfobutylether b-cyclodextrin solutions may be autoclaved.

Source and Preparation

Sulfobutylether b-cyclodextrin is prepared by alkylation of β-cyclodextrin using 1, 4-butane sultone under basic conditions. The degree of substitution in b-cyclodextrin is controlled by the stoichiometric ratio of β-cyclodextrin to sultone used in the process.

Applications

Cyclodextrins are crystalline, nonhygroscopic, cyclic oligosaccharides derived from starch. Sulfobutylether b cyclodextrin is an amorphous, anionic substituted β-cyclodextrin derivative; other substituted cyclodextrin derivatives are also available. Sulfobutylether β-cyclodextrin can form noncovalent complexes with many types of compounds including small organic molecules, peptides, and proteins.It can also enhance their solubility and stability in water.

Safety

Sulfobutylether β-cyclodextrin is derived from b-cyclodextrin, which is nephrotoxic when administered parenterally. However, studies have shown that sulfobutyletherβ-cyclodextrin is well tolerated at high doses, when administered via intravenous bolus injections, orally, and by inhalation.Up to 9 g/day may be administered by IV infusion in a licensed voriconazole formulation.The safety following high doses of sulfobutylether β-cyclodextrin intravenous administration in humans is continually being investigated. Sulfobutylether β-cyclodextrin has been subjected to an extensive battery of in vitro and in vivo genotoxicity and pharmacological evaluations. No genotoxic or mutagenic changes were observed with sulfobutylether β-cyclodextrin administration. Sulfobutylether β-cyclodextrin is biocompatible and exhibits no pharmacological activity. It is rapidly eliminated unmetabolized when administered intravenously.

Incompatibilities

The preservative activity of benzalkonium chloride is reduced in the presence of sulfobutylether β-cyclodextrin.