摘要
目的考察滤膜的固液分离能力及对药物的吸附情况,选择最佳固液分离条件,研究辅酶Q10(coenzyme Q10,CoQ10)纳米裸晶粒径与溶解度的关系。方法采用溶剂/反溶剂法制备CoQ10纳米裸晶混悬液。考察不同体积分数乙醇中,不同滤膜及其组合对药物的吸附能力和对制剂与原料药的固液分离能力。以稀释法测定CoQ10纳米裸晶与原料药在四种溶剂系统中的平衡溶解度。测定87.6nm CoQ10纳米裸晶及原料药的溶解曲线,提出"界面溶解度"的新概念,并研究粒径与界面溶解度的关系。结果滤膜的吸附能力的顺序为0.05μm PC膜>0.22μm PA膜>0.05μm PVDF膜>0.22μm PVDF膜>0.10μm PES膜,当乙醇体积分数大于等于70%时,后3种滤膜对药物均无吸附。制剂和原料药的最佳固液分离滤膜组合为0.22μm PVDF+0.05μm PVDF+0.22μmPVDF及0.22μm PVDF+0.22μm PVDF。粒径分别为114.8、85.1、77.4、58.9 nm的CoQ10纳米裸晶与原料药在4种醇水系统中的平衡溶解度分别为0.82～0.88、4.40～4.74、16.70～17.43、31.75～33.04 mg.L-1。纳米裸晶与原料药在稀释后呈现完全不同的溶解曲线,前者药物浓度迅速上升出现显著的过饱和而后下降至一个平台值;后者药物浓度逐渐增加达到相同的平台值。结论 粒径与平衡溶解度无关,与界面溶解度有关。
Objective To investigate solid-liquid separation and absorption of coenzyme Q10（CoQ10）by millipore filters,chose the best solid-liquid separation condition and study the relationship between particle size and solubility with naked CoQ10 nanocrystals under chosen conditions.Methods The precipitation method was used to prepare CoQ10 nanocrystals.The absorption was researched at different concentrations of ethanol and the solid-liquid separation was performed for both nanocrystals and bulk drugs.The dilution-dissolution method was employed to determine the equilibrium solubility of CoQ10 nanocrystals and bulk drugs in four ethanol-water solvents.The new concept of＂interfacial solubility,Sif＂was proposed and the dissolution curves of 87.6 nm CoQ10 nanocrystals and bulk drug were used to study the relationship between particle size and interfacial solubility.Results The absorption order of the drug to millipore filters was 0.05 μm PC,0.22 μm PA,0.05 μm PVDF,0.22 μm PVDF and 0.10 μm PES.The latter three filters had no absorption when the concentration of ethanol was not less than 70%（φ）.The optimal solid-liquid separation condition for nanocrystals was 0.22 μm PVDF＋0.05 μm PVDF＋0.22 μm PVDF,and for bulk drugs was 0.22 μm PVDF＋0.22 μm PVDF.The equilibrium solubility of CoQ10 nanocrystals（with particle sizes of 114.8 nm,85.1 nm,77.4 nm and 58.9 nm）and bulk drugs in four ethanol-water solvents were 0.82-0.88,4.40-4.74,16.70-17.43,31.75-33.04 mg·L-1,respectively.Under diluted conditions,the micro difference in interfacial layer between nanocrystals and bulk drug was enlarged and displayed special solublization curves.For nanocrystals,the concentration of the drug quickly increased to a supersaturated state and then decreased gradually to a plateau.While for bulk drug,the concentration of the drug increased gradually to a plateau equal to that of nanocrystals,which demonstrated the same equilibrium solubility.Conclusions The particle size is related to＂interfacial solubility＂rather than
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2011年第8期585-593,686,共10页
Journal of Shenyang Pharmaceutical University
基金
国家重点基础研究发展计划(973计划)项目(2009 CB930300)的资助
