Betadex Sulfobutyl Ether Sodium

Химические свойства

β-Cyclodextrin, sulfobutyl ethers, sodium salts is a cyclic oligosaccharide containing seven D-(t)- glucopyranose units attached by α(1→4) glucoside bonds. Sulfobutylether b-cyclodextrin is an anionic bcyclodextrin 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. Introducing the sulfobutylether (SBE) into b-cyclodextrin can produce materials with different degrees of substitution, theoretically from 1 to 21; the hepta-substituted preparation (SBE7-b-CD) is the cyclodextrin with the most desirable drug carrier properties. Sulfobutylether b-cyclodextrin occurs as a white amorphous powder.

Методы производства

Sulfobutylether β-cyclodextrin is prepared by alkylation of bcyclodextrin 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.

Оценка токсичности

Sulfobutylether b-cyclodextrin sodium (SBECD) has been associated with toxic effects in the kidney. Doses up to 1500 mg/kg produced no histopathological evidence of toxicity in dog kidneys.

Безопасность

Sulfobutylether b-cyclodextrin is derived from b-cyclodextrin, which is nephrotoxic when administered parenterally. However, studies have shown that sulfobutylether bcyclodextrin 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.

хранилище

Sulfobutylether b-cyclodextrin(182410-00-0) 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 b-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.

Несовместимости

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

Регуляторный статус

Sulfobutylether β-cyclodextrin is included in IV and IM injectable products currently approved and marketed in the USA, Europe, and Japan. It is included in the FDA Inactive Ingredients Database for IM and IV use. Its use by other routes, including SC, oral, inhalation, nasal and ophthalmic, is being evaluated in clinical studies.