【摘要】 目的 优化黄芩苷（BCN）-甘草酸（GA）纳米晶（BCN-GA-SN）的制备工艺，并进行表征和体外释放考察。方法 根据经典药对“黄芩-甘草”配伍比例，固定BCN和GA的配伍比例为6∶1(m/m)，采用沉淀法结合高压均质法制备BCN-GA纳米混悬液。以平均粒径、多分散性指数（PDI）为评价指标，以稳定剂的种类及用量、搅拌转速和时间、高压均质压力和次数为考察因素，优化BCN-GA纳米混悬液制备工艺；再以平均粒径、PDI、再分散系数（RDI）为评价指标，以冻干保护剂种类和用量为考察因素，优化BCN-GA纳米混悬液的冻干固化工艺，进而制备BCN-GA-SN；然后对BCN-GA-SN的理化性质表征和体外释放进行考察。结果BCN-GA-SN的最优制备工艺为：先以15%十二烷基硫酸钠为稳定剂，1 000 r/min搅拌15 min,100 MPa高压均质20次制备BCNGA纳米混悬液；再以5%甘露醇（相对于BCN的用量）冻干固化。所制得的BCN-GA-SN的平均粒径为（442.2±5.7） nm,PDI为0.225±0.015,RDI为1.055±0.013，呈不规则球形，大小较为均匀；该纳米晶中BCN的载药量为（62.5±0.7）%,GA的载药量为（9.4±0.2）%；体外释放结果表明，BCN-GA-SN的累积溶出度均高于BCN、GA的物理混合物。结论 本研究成功制备了BCN-GASN，其粒径大小均一、分布均匀，可有效提高BCN的体外溶出度。更多还原

【Abstract】 OBJECTIVE To optimize the preparation technology of baicalin(BCN)-glycyrrhizic acid(GA) solid nanocrystals(BCN-GA-SN), to characterize them and investigate their in vitro release characteristics. METHODS According to the compatibility ratio of classic couplet medicinals “Scutellaria baicalensis-Glycyrrhiza uralensis”, the compatibility ratio of BCN and GA was determined as 6∶1(m/m); BCN-GA nanosuspension was prepared by precipitation method combined with high-pressure homogenization method. The preparation technology of BCN-GA nanosuspension was optimized by using mean particle size and polydispersity index(PDI) as indexes and with types and dosage of stabilizers, stirring speed and time, high-pressure homogenization pressure and frequency as factors. The freeze-dried consolidation process of BCN-GA nanosuspension was optimized to prepare BCN-GA-SN using average particle size, PDI and redispersibility index(RDI) as indicators, with the type and dosage of freeze-dried protective agents as factors; then, the physicochemical properties and in vitro release of BCN-GA-SN were investigated. RESULTS The optimal preparation technology of BCN-GA-SN was as follows: BCN-GA nanosuspension was prepared by using 15% sodium dodecyl sulfate as a stabilizer, stirring at 1 000 r/min for 15 minutes, and homogenizing at 100MPa for 20 times; then, BCN-GA nanosuspension was freeze-dried and solidified with 5% mannitol(corresponding to the dosage of BCN). The average particle size of prepared BCN-GA-SN was(442.2±5.7) nm with PDI of 0.225±0.015 and RDI of 1.055±0.013. The prepared BCN-GA-SN presented as the irregularly spherical shape with more uniform size; the drug-loading amount of BCN in the nanocrystal was(62.5±0.7)%, and that of GA was(9.4±0.2)%; the in vitro release results showed that the cumulative dissolution of BCN-GA-SN was higher than that of the physical mixture of BCN and GA. CONCLUSIONS BCNGA-SN is prepared successfully in this study with uniform particle size and even distribution, which can effectively improve the dissolution of BCN.更多还原