Study of the physicochemical properties and oral bioavailability of the solid dispersion of cantharidin with polyethylene glycol 4000.

ABSTRACT

Cantharidin (CA) is partially water-soluble. Solid dispersion of CA (CA-SD) in polyethylene glycol 4000 (PEG 4000) was carried out by a solvent-fusion method to increase its dissolution rate and oral bioavailability. The physicochemical properties of this solid dispersion (SD) were evaluated immediately after preparation by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM), and the oral in vivo bioavailability was studied. In in vitro experiments CA was analyzed by high-pressure liquid chromatography (HPLC) and by gas chromatography-mass spectrometry (GC-MS) in in vivo experiments. The solubility and dissolution rate of CA were improved by the SD technique. A comparison of the pharmacokinetics between CA-SD and free CA was performed in rats. The results showed that CA-SD had a higher bioavailability than free CA after oral dosing. By comparing the AUC(0-t) of CA and CA-SD, the relative bioavailability of CA-SD to free CA was 295.4%. From these observations it could be concluded that the CA-SD has a higher absorption than pure CA and this corresponds with the dissolution result in vitro.