Study of the physicochemical properties and oral bioavailability of the solid dispersion of cantharidin with polyethylene glycol 4000.
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.
Dang
Y J
YJ
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing, China.
Hu
C H
CH
An
L N
LN
Zhu
C Y
CY
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002193:Cantharidin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D008855:Microscopy, Electron, Scanning; D011092:Polyethylene Glycols / Q000737:chemistry*; D033362:Powder Diffraction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
D004337:Drug Carriers; D004791:Enzyme Inhibitors; D011092:Polyethylene Glycols; D002193:Cantharidin