盐酸西那卡塞纳米乳的制备及体内外评价

OBJECTIVE: To improve the dissolution and oral bioavailability of cinacalcet in fasted state by preparing cinacalcet nanoemulsion. METHODS: The oil phase, emulsifiers and co-emulsifiers were selected by solubility test and phase diagram studies. The dissolution in vitro and bioavailability in Bealge dogs of cinacalcet nanoemulsion were evaluated. RESULTS: The cinacalcet nanoemulsion was prepared with oleic acid(as oil phase), OP-10 (as emulsifier), PEG200 (as co-emulsifier) and water (W-W=3:8:4:15) and showed goog physical properties with regular round appearance. The average particle size of cinacalcet nanoemulsion was (24.1±3.8) nm. The poly-dispersity index (PDI) and Zeta potential were (0.261±0.032) and (-26.1±1.7) mV, respectively, which proved that the cinacalcet nanoemulsion formed a stable system. The in vitro dissolution of cinacalcet was significantly improved after being prepared into nanoemulsion. The pharmacokinetic study showed that the bioavailability of cinacalcet nanoemulsion was significantly enhanced in Beagle dogs in fasted state and the absorbtion of cinacalcet nanoemulsion had no difference in fed and fasted state. CONCLUSION: Cinacalcet nanoemulsion is easy to prepare and has small particle size, which can significantly improve the dissolution and bioavailability of cinacalcet in fasted state.