姜黄素纳米粒冻干粉的反溶剂法制备工艺优化及溶出特征

Preparation, optimization, and dissolution characteristics of curcumin nanoparticles lyophilized powder by antisolvent method

目的优化姜黄素(Cur)纳米粒冻干粉(CNLP)制备工艺。方法以丙酮作为溶剂,去离子水作为反溶剂,聚山梨酯-80(P80)作为表面活性剂,甘露醇作为冻干保护剂通过反溶剂法制备CNLP,采用单因素分析法进行CNLP制备工艺的优化。影响CNLP粒径大小的因素有Cur质量浓度、溶剂与反溶剂体积比、表面活性剂用量、沉积时间、搅拌速率、冻干保护剂用量;得到的CNLP与原粉进行饱和溶解度和体外溶出对比实验。结果制备CNLP最优工艺为Cur质量浓度8mg/m L、溶剂与反溶剂比1∶5、表面活性剂用量0.05%、沉积时间5 min、搅拌速率400 r/min、冻干保护剂甘露醇与Cur质量比4∶1;获得的CNLP平均粒径大小为(172.2±4.6)nm;CNLP复溶液Zeta电位为(-19.7±3.7)m V;SEM图谱显示Cur原粉呈不规则的大块状,粒径在20μm左右。CNLP呈不规则的均匀块状结构,粒径在170 nm左右,与原粉相比粒径明显减小。从以上CNLP的形态来看,由激光粒度仪测得的CNLP平均粒径是基本一致的。通过饱和溶解度检测,在去离子水中,CNLP的饱和溶解度是原粉的41.32倍;在人工胃液中,CNLP饱和溶解度是原粉的1.74倍;在人工肠液中,CNLP饱和溶解度是原粉的4.11倍。通过溶出度检测,在去离子水中,CNLP的溶出速率是原粉的14.51倍;在人工胃液中,CNLP的溶出速率是原粉的2.33倍;在人工肠液中,CNLP的溶出速率是原粉的44.79倍。结论反溶剂法制备的CNLP可以改善Cur水溶性,有利于提高Cur的生物利用度。

Objective Curcumin nanoparticles lyophilized powder（CNLP） were prepared by antisolvent method which was optimized using single factor method. In this process, acetone was used as solvent, deionized water was used as antisolvent, tween-80 was used as surfactant and mannitol was used as lyoprotectant. Methods The main factors affecting the particle size of CNLP included the concentration of curcumin, volume ratio of solvent and antisolvent, dosage of surfactant, precipitation time, stirring speed, and dosage of lyoprotectant. The contrast experiments on dissolution in vitro was done between CNLP and raw curcumin powder. Results The mean particle size of CNLP was（172.2 ± 4.6） nm; The Zeta potential of CNLP redissolving in water was（-19.7 ± 3.7） m V. The SEM graphs indicated the raw curcumin was in irregular and massive shape and its particle size was about 20μm. The CNLP exhibited regular block structure and its particle size was about 170 nm which was obviously reduced compared with raw curcumin. The mean particle size of CNLP obtained from laser particle analyzer was in accord with the morphology of CNLP.The saturated solubility of CNLP was 41.32 times of raw curcumin powder in deionized water, 1.74 times in simulated gastric fluid and 4.11 times in simulated intestinal fluid through saturated solubility test, respectively. The dissolution rate of CNLP was 14.51 times of raw curcumin powder in water dissolution medium, 2.33 times in simulated gastric fluid and 44.79 times in simulated intestinal fluid through dissolution determination, respectively. Conclusion The preparation process of CNLP using antisolvent method could improve the drawback of poor water solubility and enhance the bioavailability of curcumin.