摘要
目的:制备氧化苦参碱磷脂复合物固体脂质纳米粒(OMT-PC-SLN)冻干粉,并对其进行药剂学性质评价。方法:采用伪三元相图优选微乳处方;以包封率为指标,采用单因素试验优选OMT-PC-SLN冻干粉的处方工艺;利用透射电子显微镜(TEM)观察该制剂的外观形态,激光粒度仪测定粒径,并考察OMT-PC-SLN冻干粉的体外释药性能。结果:最佳处方工艺为大豆磷脂和15-羟基硬脂酸聚乙二醇酯(Kolliphor HS 15)为乳化剂,乙醇为助乳化剂,乳化剂与助乳化剂的比例(Km)=3∶2,油相∶(乳化剂+助乳化剂)=1∶9,氧化苦参碱磷脂复合物-硬脂酸-大豆磷脂-Kolliphor HS 15-乙醇(30∶100∶180∶360∶360);含4%甘露醇的水50 m L为外水相,1 000 r·min-1冰浴搅拌固化1 h,于-20℃预冻24 h,取出,干燥24 h。OMT-PC-SLN冻干粉外观呈类球形,包封率(38. 09±1. 24)%,平均粒径785. 5 nm,多分散系数(PDI) 0. 456,Zeta电位-24. 82 m V;体外释放结果表明OMT-PC-SLN冻干粉2 h时累积释放率72. 63%,12 h累积释放率98. 42%,原料药在2 h的累积释放率98. 60%。结论:优选的OMT-PC-SLN冻干粉处方工艺稳定、重复性好;与原料药相比,OMT-PC-SLN冻干粉体外释放较慢,具有一定的缓释效果。
Objective: To prepare oxymatrine phospholipid complex solid lipid nanoparticles( OMT-PCSLN) lyophilized powder and evaluate its pharmaceutical properties. Method: Pseudo-ternary phase diagram was employed to optimize the formula of microemulsion; single factor experiments were adopted to optimize the formulation process of OMT-PC-SLN lyophilized powder with encapsulation efficiency as index; the morphology of this preparation was observed by transmission electron microscope( TEM). The particle size was measured by particle size analyzer and the in vitro release performance of OMT-PC-SLN lyophilized powder was examined.Result: Optimal formulation process was as following: taking soybean phospholipid and polyethylene glycol 15-hydroxystearate( Kolliphor HS 15) as the emulsifier,ethanol as co-emulsifier,ratio of emulsifier to co-emulsifier( Km) = 3 ∶ 2,oil phase ∶( emulsifier + co-emulsifier) = 1 ∶ 9,oxymatrine phospholipid complex-stearic acidsoybean phospholipid-Kolliphor HS 15-ethanol( 30 ∶ 100 ∶ 180 ∶ 360 ∶ 360); taking 50 m L of 4% mannitol solution as the external aqueous phase,ice bath stirring at 1 000 r·min-1 and solidifying for 1 h,precooled at-20 ℃ for24 h, took out and dried for 24 h. OMT-PC-SLN lyophilized powder was spherical in appearance with encapsulation efficiency of( 38. 09 ± 1. 24) %, average particle size of 785. 5 nm, polydispersity coefficient( PDI) of 0. 456 and the Zeta potential of-24. 82 m V. The cumulative release rates of OMT-PC-SLN lyophilized powder were 72. 63% at 2 h and 98. 42% at 12 h; the cumulative release rate of oxymatrine( crude drug) was98. 60% at 2 h. Conclusion: This optimized formulation process of OMT-PC-SLN lyophilized powder is stable with good repeatability; compared with oxymatrine,OMT-PC-SLN lyophilized powder has a certain sustained-release effect.
引文
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