过程参数对SAS法制备紫杉醇DDS微粒的影响

发布时间：2018-05-16 12:28

  本文选题：超临界反溶剂 + 药物输送系统　； 参考：《华南理工大学》2010年硕士论文

【摘要】： 紫杉醇是临床上最有效的抗癌药物之一,但水溶性极低,且在大多数医用溶媒中不溶解或者溶解度较低,现行制剂以无水乙醇和聚乙烯基蓖麻油(v/v,50/50)混合物为溶剂,具有很大的毒副作用。因此,紫杉醇新剂型的研制成为热点。超临界反溶剂(Supercritical anti-solvent, SAS)法通过预设不同的操作参数,可有效控制药物输送系统(Drug delivery system,DDS)微粒的粒径及其分布,是低溶剂残留的DDS绿色制备新技术。本论文以紫杉醇为模型药物,研究各过程参数对SAS法制备DDS的影响。 本文通过单因素实验,以DCM/无水乙醇(EtOH)、DCM/二甲亚砜(DMSO)混合溶液为溶剂,采用SAS法成功制备出紫杉醇DDS微粒;借助扫描电镜(SEM)、激光粒度仪和高效液相色谱等检测手段对DDS微粒进行表征,考察了混和溶剂体系下,过程参数包括压力、温度、溶剂配比、溶液流速和溶质浓度等对DDS微粒的形貌、粒径和包封率的影响。 结果表明,所得紫杉醇DDS微粒的形貌受溶剂性质影响较大,在DCM中加入EtOH有助于改善DDS微粒的表面光滑程度;而当加入DMSO时DDS微粒出现孔状结构,且分散度较差。在实验范围内,增加压力(80-140bar),所得DDS微粒的粒径和包封率增加;增加温度(30-45℃),所得DDS微粒的粒径呈上升趋势。在DCM/EtOH体系中,DDS微粒包封率随温度升高而增加,而在DCM/DMSO溶剂体系中,包封率随温度升高先增加后降低;当温度高于40℃时,微粒之间聚集,甚至形成膜状物质。样品溶液流速增大DDS微粒的平均粒径随之增大。当载体聚乳酸(PLLA)与PTX浓度之比为5:1时,获得DDS微粒的包封率较高为86.8%。 上述研究工作可为SAS法成功制备DDS微粒提供参考。
[Abstract]:Paclitaxel is one of the most effective anticancer drugs in clinic, but its water solubility is very low, and it is insoluble or low solubility in most medical solvent. Have great toxic side effects. Therefore, the development of a new dosage form of paclitaxel has become a hot spot. Supercritical antisolvent supercritical anti-solvent (Sass) method can effectively control the particle size and distribution of drug delivery system by preset different operating parameters. It is a new green preparation technique for low solvent residual DDS. In this paper, paclitaxel was used as model drug to study the effect of various process parameters on the preparation of DDS by SAS method. In this paper, paclitaxel DDS particles were successfully prepared by SAS method in the mixed solution of DCM/ anhydrous ethanol (et OHH) and DMSO (dimethyl sulfoxide) as solvent. DDS particles were characterized by scanning electron microscope (SEM), laser particle size analyzer and high performance liquid chromatography (HPLC). The process parameters including pressure, temperature and solvent ratio were investigated in the mixed solvent system. The effects of solution flow rate and solute concentration on the morphology, particle size and encapsulation efficiency of DDS particles. The results show that the morphology of the obtained DDS particles is greatly affected by the solvent properties, and the addition of EtOH to DCM can improve the surface smoothness of DDS particles, while when DMSO is added, the pore structure of DDS particles is observed, and the dispersion of DDS particles is poor. In the range of experiment, the particle size and encapsulation efficiency of DDS particles increased with the increase of pressure (80-140), and the particle size of DDS particles increased with the increase of temperature from 30 鈩，

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