The Preparation And Evaluation Of Prsugrel Inclusion Compound

Objective:Preparing prasugrel into prasugrel-hydroxypropyl-β-cyclodextrin inclusion compound, so as to improve the dissolubility and raise bioavailability.Methods:prasugrel-hydroxypropyl-β-cyclodextrin inclusion compounds were prepared and the preparation conditions were optimized by single-factor experiment and orthogonal design, regarding entrapment efficiency as evaluation index. Then, the Prasugrel-hydroxypropyl-β-cyclodextrin inclusion compound was characterized by infrared spectroscopic analysis, x-ray diffraction analysis and differential scanning calorimetry analysis. HPLC method was established to measure the solubility and dissolution rate of prasugrel-hydroxypropyl-β-cyclodextrin inclusion compound. SD mice were laveged prasugrel suspension and suspension of prasugrel-hydroxypropyl-β-cyclodextrin inclusion compound, respectively. The serum concentration of prasugrel were measured by HPLC, and the pharmacokinetics parameters were also calculated by Thermo Kinetica Softwave Version 5.0.Results:The best preparation formulation of inclusion compounds was 300 r·min-1 stirring rate,1 hour mixing time,50 ℃ mixing temperature. Prasugrel and prasugrel-hydroxypropyl-β-cyclodextrin inclusion compound were confirmed by means of infra-red spectroscopic analysis, x-ray diffraction analysis and differential scanning calorimeter. Compared with active pharmaceutical ingredient, solubility of prasugrel-hydroxypropyl-β-cyclodextrin inclusion compound improved 4.42 times. The dissolution rate of prasugrel-hydroxypropyl-β-cyclodextrin inclusion compound was obvious higher than that of active pharmaceutical ingredient in pH4.0 phosphate buffered solution, pH 6.8 phosphate buffered solution and distilled water, respectively. Compared with prasugrel, the Cmax, Tmax, and T1/2 of prasugrel-hydroxypropyl-β-cyclodextrin inclusion compound were increased from 0.511 ±0.017μg·ml-1,1±0.267,1.98±18.082 h to 2.045±0.125 μg·ml-1,0.5± 0.193 h,2.63±10.352 h, respectively, and AUC was increased from 101.723± 13.541 μg·h·ml-1 to 286.833±2.026 μg·h·ml-1.Conclusion:The preparation method of inclusion compounds was simple, which can significantly improve the solubility and dissolution ofprasugrel. The results of pharmacokinetic studies of SD mice indicated that the prasugrel-hydroxypropyl-β-cyclodextrin inclusion compound could raise the absorption of prasugrel, so as to increase the oral bioavailability.