Effect of SBE4-β-CD, a sulfobutyl ether β-cyclodextrin, on the stability and solubility of O6-benzylguanine (NSC-637037) in aqueous solutions

Cyclodextrin Drug Carrier Systems

“…This hydrolysis at pH 4.8 was decelerated by a factor of 220 by the complexation with sulfobutyl-β-cyclodextrin with an average degree of substitution of ∼4, because of the unfavorable charge separation in the hydrophobic cavity of the cyclodextrin. 101 Our recent results suggest that the stoichiometry of cyclodextrin complexes affects chemical reactivities of guests. An antiulcer agent, 2′-(carboxymethoxy)-4,4′-bis((3-methyl-2-butenyl)oxy)chalcone, formed the 1:1 complex with cyclodextrins at lower concentrations of the host and the 1:2 (guest:host) complex at higher concentrations.…”

“…An antitumor drug, O 6 -benzylguanine, undergoes acid-catalyzed hydrolysis to form guanine and benzyl alcohol according to an S N 1 mechanism with significant charge separation in the rate-determining step. This hydrolysis at pH 4.8 was decelerated by a factor of 220 by the complexation with sulfobutyl-β-cyclodextrin with an average degree of substitution of ∼4, because of the unfavorable charge separation in the hydrophobic cavity of the cyclodextrin 4 Acid-catalyzed hydrolysis of the glycoside bonds in digoxin. …”

Pharmaceutical Applications of Cyclodextrins. 1. Drug Solubilization and Stabilization

“…The benzyl moiety of the drug was responsible for the cyclodextrin complex formation resulting in an objective increased shelf-life of an aqueous parenteral O 6 -benzylguanine formulation. 71 The same cyclodextrin derivative has been used to increase the shelf-life (and ocular absorption) of pilocarpine in aqueous eye drop solutions. 91 The cyclodextrin stabilization of pilocarpine appeared to be independent of the drug ionization status.…”

“…Sulfobutyl ether -cyclodextrin, where the anion has been moved away from the cavity by a butyl ether spacer group, is an excellent solubilizer. 71 (Carboxymethyl)--cyclodextrin is another interesting anionic cyclodextrin derivative. 72 Compared to neutral cyclodextrins, enhanced complexation is frequently observed when the drug and cyclodextrin molecules have opposite charge but decreased complexation is observed if they carry same type of charge.…”

Cyclodextrin Based Spectral Changes

“…Moreover the cavity microenvironment of CyDs may alter the rate constant of reactions for the guest molecules depend on the reaction, substrate and the differences between cavity and solvent environments [51][52][53]. The changes in reaction rate cause to spectral time profile of the substrate and may be applicable in selective kinetic measurement of substrates and their recognition [54,55].…”