目的 制备盐酸西那卡塞纳米乳,提高其体外溶出度及空腹下口服生物利用度。方法 通过溶解度测定,选择溶解盐酸西那卡塞能力较强的油相,乳化剂和助乳化剂,观察纳米乳的形成并绘制伪三元相图比较纳米乳区域的大小以确定辅料种类及Km值,对盐酸西那卡塞纳米乳进行体外评价并研究其在Beagle犬体内的药动学。结果 以油酸(油相)-OP-10(乳化剂)-PEG200(助乳化剂)-水(质量比为3:8:4:15)制得的纳米乳性状良好,呈规则圆球状,平均粒径为(24.1±3.8)nm,PDI为(0.261±0.032),Zeta电位为(-26.1±1.7)mV,体系稳定。自制盐酸西那卡塞纳米乳和市售片剂相比,其在体外溶出度显著提高,达到95%以上。药动学研究表明,自制盐酸西那卡塞纳米乳在Beagle犬体内的空腹生物利用度明显提高,空饱腹吸收差异减小。结论 盐酸西那卡塞纳米乳制备简单,纳米乳粒径小,可显著提高盐酸西那卡塞的体外溶出度及空腹下的口服生物利用度。
Abstract
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.
关键词
盐酸西那卡塞 /
纳米乳 /
伪三元相图 /
体外溶出度 /
空腹生物利用度
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Key words
cinacalcet /
nanoemulsion /
pseudo ternary phase diagram /
dissolution /
bioavailability in fasted state
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中图分类号:
R944
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参考文献
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