苦参总生物碱固体脂质纳米粒的制备工艺研究

目的探索苦参总生物碱(TA)磷脂复合物固体脂质纳米粒(TA-PC-SLN)的制备工艺及处方优化,并对其进行体外评价。方法建立高效液相色谱(HPLC)法同时测定TA中4个指标成分苦参碱(MT)、氧化苦参碱(OMT)、槐果碱(SC)、氧化槐果碱(OSC),并进行方法学验证。称取TA、卵磷脂共同溶于乙醇制备磷脂复合物;采用微乳法制备TA-PC-SLN。采用超速离心结合HPLC法考察包封率和载药量;比色法检测粒径分布及Zeta电位。以包封率和载药量作为TA-PC-SLN考察指标,用星点-效应面法优化处方,同时评价TA-PC-SLN的体外释放。结果 HPLC色谱条件为:DIKMA C₁₈色谱柱(250 mm×4.6 mm,5μm);流动相为乙腈-0.05 mo L/L的KH₂PO₄(含2 mL/L三乙胺)溶液,梯度洗脱,洗脱条件为0 min(6%乙腈)→35 min(13%乙腈)→40 min(6%乙腈),检测波长为220 nm。TA-PC-SLN的平均粒径为(126.1±3.89) nm,粒径分布(PDI)为(0.409±0.022),Zeta电位为(-30.9±7.37)m V;TA-PC-SLN最佳的制备工艺处方为:药物磷脂复合物与水相(泊洛沙姆,大豆卵磷脂和聚乙二醇2 000组成)比例为1∶1.75,大豆卵磷脂和聚乙二醇2 000比例为1∶1.25,冰水分散相与微乳体积比例为9∶1。TA-PC-SLN体外释放速率低于TA。结论制备出的TA-PC-SLN包封率可达到74%以上,载药量可达到9%以上,并且实现了缓释的目的。

Study on preparation technology of solid lipid nanoparticles of total alkaloids of Sophora flavesticus

Objective The preparation and formulation optimization of solid lipid nanoparticles of total alkaloids of Sophora flavesicum (TA-PC-SLN) were explored and completed,and the in vitro evaluation of the solid lipid nanoparticles was conducted.Methods HPLC was used to establish a method for simultaneous determination of four index components——matrine (MT),oxymatrine (OMT),sophocarpine (SC),oxysophocarpine (OSC) in TA.The methodology was validated.TA and lecithin were dissolved in ethanol to prepare phospholipid complex,and TA-PC-SLN was prepared by microemulsion method.The entrapment efficiency and drug loading were determined by ultracentrifugation combined with HPLC,and the particle size distribution and zeta potential were determined by colorimetry.The inclusion rate and drug loading were used as the indexes.The formulation was optimized by the star-point effect-surface method,and the dissolution rate of TA-PC-SLN was evaluated in vitro.Results HPLC conditions:DIKMA C₁₈column (250 mm×4.6 mm,5μm);mobile phase:acetonitrile-0.05 mol/L KH₂PO₄(containing 2 mL/L triethylamine) solution,gradient elution,elution conditions:0 min (6%acetonitrile)→35 min (13%acetonitrile)→40 min (6%acetonitrile);detection wavelength:220 nm.The average particle size of ta-pc-sln was (126.1±3.89) nm,PDI was (0.409±0.022),and zeta potential was (-30.9±7.37) mV;The optimal formulation was:the ratio of the pharmaceutical phospholipid complex to the aqueous phase (polloxam,soybean lecithin and polyethylene glycol 2000) was 1:1.75,the ratio of soybean lecithin to polyethylene glycol 2000 was 1:1.25,and the ratio of the ice-water dispersed phase to the volume of microemulsion was 9:1.The release rate of solid lipid nanoparticles was much lower than that of total alkaloids of sophora flavescens.Conclusion TA-PC-SLN can achieve the encapsulation rate of over 74%and the drug load of over 9%,the aim of slow release of total alkaloids of sophora flavescens was realized.