高良姜素过饱和自纳米乳的制备及质量评价

Preparation and quality evaluation of galangin supersaturating self-nanoemulsifier

目的研究高良姜素过饱和自纳米乳递药系统(galangin-SSNEDDS)的处方组成,并进行评价。方法通过溶解度试验、配伍试验及伪三元相图,筛选高良姜素自纳米乳处方,运用星点设计-效应面法优化处方;再以粒径、抑晶效果及溶出试验等考察高良姜素过饱和自纳米乳处方并对其进行理化性质及稳定性等评价。结果优化得到的高良姜素过饱和自纳米乳处方中油相为油酸聚乙二醇甘油酯(26.68%)、表面活性剂为聚氧乙烯蓖麻油(49.67%)、助表面活性剂为聚乙二醇400(23.65%)、促过饱和物质为聚乙烯己内酰胺-聚醋酸乙烯酯-聚乙二醇接枝共聚物(Soluplus)(3.0 mg·g^(-1)),载药量为28.0 mg·g^(-1)。高良姜素过饱和自纳米乳为金黄色透明黏稠液体,分散液为O/W型乳液,乳化时间为(67±4)s,平均粒径为(29.96±0.71)nm,PDI为(0.230±0.007),电位为(-6.00±0.63)mV。高良姜素过饱和自纳米乳稳定性良好,可在2 h内维持较高的过饱和度,有效避免药物结晶析出,显著提高原料药的释放量。结论高良姜素过饱和自纳米乳制备工艺简单,粒径分布均匀,稳定性好,能有效提高高良姜素的体外释放度,抑制结晶析出,有望提高高良姜素的生物利用度。

Objective To determine and evaluate the formulation of galangin supersaturating self-nanoemulsifying drug delivery systems(galangin-SSNEDDS).Methods The formulation of galangin-SNEDDS was settled by solubility test,compatibility test,pseudo-ternary phase diagram and central composite design-response surface methodology.The formulation of galangin-SSNEDDS was evaluated with particle size,crystal inhibition effect and dissolution test.The physicochemical properties and stability of galangin-SSNEDDS were also evaluated.Results In the optimized galangin-SSNEDDS formulation,the oil phase was Labrafil M1944CS(26.68%),the emulsifier was Kolliphor ELP(49.67%),the coemulsifier was PEG 400(23.65%),the supersaturated promoter was Soluplus(3.0 mg·g^(-1))and the drug loading was 28.0 mg·g^(-1).Galangin-SSNEDDS presented as golden yellow transparent viscous liquid.The dispersion was O/W emulsion,the emulsification time was(67±4)s,the average particle size was(29.96±0.71)nm,the PDI was(0.230±0.007),and the potential was(-6.00±0.63)mV.Galangin-SSNEDDS showed good stability,which maintained high supersaturation within 2 h,effectively avoided drug crystallization,and significantly increased the bulk drug release.Conclusion Galangin-SSNEDDS has the advantages of simple preparation process,uniform particle size distribution and good stability.It can effectively improve the release of galangin in vitro and inhibit the crystallization,which helps improve the bioavailability of galangin.