Technology

Captisol Chemistry

Cyclodextrins (CDs) are cyclic oligosaccharides typically containing 6(α-CD), 7(β-CD), or 8(γ-CD) glucopyranose units, oriented in a truncated cone structure with a hydrophilic on the exterior and a lipophilic interior. This lipophilic interior can then partially or fully contain an insoluble guest molecule, forming a cyclodextrin complex with better solubility and/or stability than the guest molecule. Typical α-, β-, and γ-cyclodextrins (particularly β) have limited aqueous solubility and show toxicity when given by injection, so Captisol® was derivatized from a β-cyclodextrin to have ~6.5 sulfobutylether groups per cyclodextrin molecule, to generate a parenterally safe CD-derivative.

These sulfobutylether groups make Captisol® unique:

• The very low pKa of the sulfonic acid groups results in multiple negative charges at physiologically compatible pH values, greatly increasing the solubility & safety of the cyclodextrin & provides another "handle" by which molecules can interact with Captisol.
• Captisol can increase water solubility by 10x to 150,000x depending on compound structure, concentration of Captisol®, pH effects on the extent of drug ionization, buffer selection and strength of complex.
• Aqueous formulations with Captisol are often simpler & less toxic than the use of organic solvents, surfactants, and extreme pH conditions to achieve desired dosages.
• Stability of drugs in aqueous solution may be improved on with Captisol. Enclosure of the labile area of the drug in the cyclodextrin cavity or interaction with the SBE substituent can reduce decomposition rate by ‘hiding’ the reactive center.
• The four-carbon butyl chain coupled with the repulsion of the end group negative charges allows for an "extension" of the cyclodextrin cavity, often resulting in stronger binding than other modified cyclodextrins.
• Complexation is a non-covalent, reversible interaction typically occurring in a 1:1 stoichiometry.