Improvement of glibenclamide bioavailability using cyclodextrin inclusion complex dispersed in polyethylene glycol

Abstract EN

The specific aim of this study was to improve the aqueous solubility of the oral hypoglycemic agent, glibenclamide, so that to improve its oral absorption, and hence bioavailability after oral administration.

This was accomplished by complex formation between glibenclamide and β-cyclodextrin (β-CD) and dispersion in polyethylene glycol 6000 (PEG 6000).

Differential Scanning Calorimetry (DSC) and X-Ray Diffractometry (XRD) results confirmed the complex formation between glibenclamide and β-CD.

The solubility of glibenclamide increased as a function of increasing the concentration of β-CD and PEG 6000.

The dissolution rate of glibenclamide from the prepared complex was more rapid than that from the commercial brand Glibil 5® and the physical mixture of the pure components.

The oral bioavailability of the prepared formulation was investigated by administration to 12 rabbits and compared to that of Glibil 5®.

The proposed formulation produced higher bioavailability compared to Glibil 5® in terms of the maximum plasma concentration (Cmax) and the area under the curve (AUC) where they were significantly higher compared to those after administration of Glibil 5®.

Our results confirmed that the oral bioavailability of glibenclamide was significantly improved by complexation with β-CD and dispersion in PEG 6000.

Therefore, it can be concluded that PEG 6000 increases the solubilizing effect of β-CD, and hence, reducing the amount of β-CD needed to prepare such a solid dosage form of glibenclamide.