Sulfobutylether beta-cyclodextrin

• USP–NFBetadex Sulfobutyl Ether Sodium

Captisol; Dexolve; SBECD; SBE-β-CD; sulfobutyl betadex sodium; betadex sulfobutyl ether sodium

β-Cyclodextrin sulfobutyl ether, sodium salt (average degree of substitution about 6.5) · [182410-00-0]

C42H70−nO35·(C4H8SO3Na)n, n ≈ 6.5 · ≈ 2160 (for n = 6.5)

Solubilising agent

Typical concentrations: — · Dosage forms: Sterile (parenteral/ophthalmic)

Used to solubilise and stabilise poorly water-soluble drugs by forming inclusion complexes, chiefly in intravenous and intramuscular injections and also in oral, ophthalmic and inhalation products. Marketed injections such as voriconazole, ziprasidone, amiodarone and remdesivir rely on it; the concentration depends on the drug dose and binding constant, and reconstituted parenteral solutions commonly contain about 15–30% w/v.

White to off-white, amorphous, practically odourless powder. It is a mixture of β-cyclodextrin molecules carrying different numbers of sodium sulfobutyl ether groups on their hydroxyl positions, which make the molecule highly water-soluble and anionic.

Average degree of substitution

about 6.2–6.9 sulfobutyl groups per cyclodextrin molecule

Solubility

very soluble in water (well over 50 g per 100 mL); practically insoluble in ethanol and most organic solvents

pH

about 4–7 (aqueous solution)

Hygroscopicity

hygroscopic; amorphous material

Ionic character

polyanionic; the sulfonate groups remain ionised over the whole pharmaceutical pH range

The solid is stable but hygroscopic and should be stored in a tightly closed container protected from moisture. Aqueous solutions are chemically stable and can be sterilised by autoclaving or filtration.

Can complex preservatives and other formulation components, which may reduce their effective concentration. Being polyanionic, it may interact with cationic drugs and excipients; competitive displacement by other guest molecules can alter drug solubilisation.

Produced by reacting β-cyclodextrin with 1,4-butane sultone in aqueous alkaline solution. The product is purified, for example by ultrafiltration and carbon treatment, to remove residual reagents and unsubstituted cyclodextrin, and is then dried to a powder.

Well tolerated after parenteral and oral administration; unlike parent β-cyclodextrin it shows little nephrotoxicity. It is eliminated unchanged by the kidneys, so it accumulates in patients with renal impairment; for this reason the labels of some intravenous products advise caution or alternative therapy in moderate to severe renal impairment. Renal tubular vacuolation has been seen in animals at high doses.

Observe normal precautions for the quantity handled. Avoid inhaling the dust; eye protection and gloves are recommended.

Included in the FDA Inactive Ingredient Database (intravenous and intramuscular injections; oral preparations) and in medicines approved in the USA, Europe and elsewhere.

Alfadex; betadex; gammadex; hydroxypropyl betadex; methyl betadex.

The degree and pattern of substitution affect complexation, so material from different sources is not automatically interchangeable. Phase-solubility studies are used to choose the minimum cyclodextrin level; excess cyclodextrin adds osmolality and can reduce membrane permeation of the drug.