Improving glyburide solubility and dissolution by complexation with hydroxybutenyl-beta-cyclodextrin.

Objectives: Glyburide, an important drug for type 2 diabetes, has extremely poor aqueous solubility and resulting low bioavailability. This study describes the ability of hydroxybutenyl-beta-cyclodextrin (HBenBCD) to form complexes with glyburide, with enhanced solubility and dissolution rate in vitro.

Method: Glyburide and glyburide-HBenBCD were evaluated in various test media known to simulate human gastrointestinal conditions in the fasted and fed states, respectively.

Solubilization and dissolution of tamoxifen-hydroxybutenyl cyclodextrin complexes.

The solubility and dissolution of tamoxifen base and tamoxifen citrate with and without hydroxybutenyl-beta-cyclodextrin (HBenBCD) in aqueous and organic media were examined. The solubility of tamoxifen was greatly enhanced by complexation with HBenBCD; pH of the medium, and choice of buffer significantly impacted the amount of drug that could be solubilized. Different tamoxifen:HBenBCD formulations were prepared, including liquid fill capsule formulations, and their dissolution profiles were obtained.

Synthesis and characterization of water-soluble hydroxybutenyl cyclomaltooligosaccharides (cyclodextrins).

We have examined the synthesis of hydroxybutenyl cyclomaltooligosaccharides (cyclodextrins) and the ability of these cyclodextrin ethers to form guest-host complexes with guest molecules. The hydroxybutenyl cyclodextrin ethers were prepared by a base-catalyzed reaction of 3,4-epoxy-1-butene with the parent cyclodextrins in an aqueous medium. Reaction byproducts were removed by nanofiltration before the hydroxybutenyl cyclodextrins were isolated by co-evaporation of water-EtOH.