Preparation of inclusion complex of praziquantel with 2-hydroxypropyl-β-cyclodextrin and pharmacokinetic property improvement

Abstract

An inclusion complex of praziquantel with 2-hydroxypropyl-β-cyclodextrin was designed and prepared by an optimized method and the inclusion complex was characterized by infrared absorption spectral, proton NMR spectral and scanning electron image studies. It was shown that the aqueous solubility of praziquantel has increased (~104 fold) in comparison with praziquantel alone, which is the best result so far for praziquantel solubility study. The in vivo pharmacokinetic properties of praziquantel in dogs such as Cmax, Tmax, AUC0-∞, and t1/2 have been improved significantly after complexation. The increased water solubility of the praziquantel in the complex resulted in the improved values of Cmax (4.82 μg/mL vs 0.51 μg/mL, 9.45 fold higher) and AUC0-∞ (98.06 μg h/mL vs 20.63 μg h/mL, 4.75 fold higher) in dog pharmacokinetic studies, which is useful to find a new praziquantel formulation as an anti-schistosomal agent.

Keywords

• Inclusion complex
• Praziquantel
• 2-Hydroxypropyl-β-cyclodextrin
• Pharmacokinetic property evaluation