In vitro and in vivo studies on the complexes of glipizide with water-soluble β-cyclodextrin-epichlorohydrin polymers

The purpose of this study was to evaluate the potential of a newly modified cyclodextrin derivative, water-soluble beta-cyclodextrin-epichlorohydrin polymer (beta-CDP), as an effective drug carrier to enhance the dissolution rate and oral bioavailability of glipizide as a poorly water-soluble model drug. Inclusion complexes of glipizide with beta-CDP were prepared by the co-evaporation method and characterized by phase solubility, dissolution, and differential scanning calorimetry. The solubility curve was classified as type A L, which indicated the formation of 1:1 complex between glipizide and beta-CDP. beta-CDP had better properties of increasing the aqueous solubility of glipizide compared with HP-beta-CD. The dissolution rate of drug from the beta-CDP complexes was significantly greater than that of the corresponding physical mixtures indicating that the formation of amorphous complex increased the solubility of glipizide. Moreover, the increment in drug dissolution rate from the glipizide/beta-CDP systems was higher than that from the corresponding ones with HP-beta-CD, which indicated that beta-CDP could provide greater capability of solubilization for poorly soluble drugs. Furthermore, in vivo study revealed that the bioavailability of glipizide was significantly improved by glipizide/beta-CDP inclusion complex after oral administration to beagle dogs.