Comparative study of preparation, characterization and pharmacokinetics of three preparations of osthole / 中草药

ABSTRACT

Objective: To prepare osthole solid dispersions (Ost-SD), osthole phospholipids complex (Ost-PC), and osthole nanosuspensions (Ost-NS), and compare their effects on the pharmacokinetics in SD rats in vivo. Methods: Solvent evaporation method was used to prepare Ost-SD and Ost-PC. Their existential state of Ost in Ost-SD and Ost-PC were analyzed by X-ray power diffraction (XRPD). High pressure homogenization method was employed to prepare Ost-NS, its particle size and Zeta potential were studied. The dissolution in vitro of Ost-SD, Ost-PC, and Ost-NS were also studied compared to Ost suspension. SD rats in each group were ig administered with Ost, Ost-SD, Ost-PC, and Ost-NS, respectively. The concentration of Ost in blood was analyzed by HPLC, and the main pharmacokinetic parameters were obtained. The pharmacokinetic behavior and bioavailability were also been compared. Results: The results of XRPD indicated that Ost showed an amorphous state in Ost-SD and Ost-PC. The average particle size and Zeta potential of Ost-NS were (161.37 ± 3.77) nm and (-29.16 ± 1.83) mV, respectively. The results of dissolution in vitro indicated that the dissolution of Ost was improved greatly by Ost-SD, Ost-PC, and Ost-NS. The results of pharmacokinetics in vivo showed that Cmax, AUC0~t and AUC0~∞ of Ost-SD, Ost-PC, and Ost-NS were enhanced greatly compared to Ost. The bioavailability of Ost-SD, Ost-PC,and Ost-NS were enhanced to 165.92%, 138.46%, and 259.35%, respectively. Conclusion: Ost-SD, Ost-PC, and Ost-NS can enhance the bioavailability of Ost in SD rats notably. In addition, Ost-NS can give a better effect.