Repaglinide-Cyclodextrin complexes: Preparation, Characterization and in vivo evaluation of antihyperglycemic activity

The influence of β-cyclodextrin (βCD) and its hydrophilic derivative hydroxypropyl-β-cyclodextrin (HPβCD) on the in vitro dissolution rate and in vivo antihyperglycemic activity of a poorly water soluble drug, repaglinide (RPG) was studied. Solid dispersions of RPG were prepared by various methods such as physical mixing, cogrinding, kneading, and coevaporation. The dispersions were characterized by differential scanning calorimetry (DSC), X-ray diffraction patterns, infrared spectroscopy, nuclear magnetic resonance studies and optical microscopy. The DSC thermogram of HPβCD dispersion indicated complete disappearance of melting endotherm of RPG indicating complete amorphization. The dispersions exhibited faster rates of dissolution compared to that of physical mixtures. The kneaded dispersion with HPβCD exhibited the fastest in vitro dissolution rate when compared to other dispersions. In vivo studies revealed that the kneaded dispersions with βCD and HPβCD showed significant improvement in antihyperglycemic activity as compared to RPG alone, thus confirming the advantage of improved pharmacological activity of RPG when administered as a solid dispersion with cyclodextrin.