雷洛昔芬纳米乳的处方设计

Prescription Design of Raloxifene Nanoemulsion

目的研究雷洛昔芬纳米乳的处方设计。方法考察雷洛昔芬在纳米乳辅料中的溶解度;在此基础上,通过乳化能力筛选出适合的乳化剂与油;助乳化剂与油、乳化剂三者之间的组合及最佳比例由伪三元相图确定;通过载药量考察雷洛昔芬对纳米乳处方的影响;采用壳聚糖、羧化壳聚糖调节纳米乳Zeta电位;通过测定粒径评价载药纳米乳在不同稀释倍数及不同pH缓冲盐中的稳定性。结果雷洛昔芬纳米乳最佳处方为亚油酸(LOA)-棕榈酸异丙酯(IPP)-聚氧乙烯氢化蓖麻油(RH40)-乙醇(0. 167 g∶0. 333 g∶0. 3 g∶0. 2 g),载药量为15 mg;壳聚糖及羧化壳聚糖可分别使纳米乳的Zeta电位从原来的-0. 95 mV变为20 mV及-13 mV左右;不同pH及稀释倍数对3种纳米乳的稳定性影响不大。结论通过系统研究,获得了Zeta电位分别为正值、负值及接近零的3个雷洛昔芬纳米乳处方,为后期雷洛昔芬纳米乳吸收机制的研究奠定了基础。

OBJECTIVE To study formulation design of raloxifene nanoemulsion. METHODS The solubilities of raloxifene in excipients of nanoemulsion were investigated. On the basis, emulsifier and oil were selected by the emulsifying ability. The combination anti optimum proportion among co-emulsifier, oil and emulsifier were determined by the pseudu-ternary phase diagram. The effect of raloxitene on nanoemulsion prescription was studied by drug loading. Finally chitosan and carboxylated chitosan were used to regulate the Zeta potential of raloxifenc nanoemulsions. RESULTS The optimum formulation ratio of LOA, IPP, RH40 and ethanol for loading 15 mg raloxifene is 0. 167 g： 0. 333 g： 0.3 g： 0.2 g, respectively. The Zeta potentials of the nanoemulsions can be changed by chitosan and carboxylated chitosan from -0. 954 mV to 20 mV and - 13 mV or so,respectively. The effect of different pH and dilution times on stability of formulations were slight. CONCLUSION The formulations of raloxifene nanoemulsion including positive, negative and near zero Zeta potential were obtained, which have laid a foundation for absorption mechanism study of the raloxifene nanoemulsion.