湿法纳米研磨制备药物纳米晶体--铝碳酸镁  

Preparation of pharmaceutical nanocrystals using wet nanomilling-Hydrotalcite

作　　者：王小康 张扬[2] FALOLA Akinola 何运良 王学重 WANG Xiaokang;ZHANG Yang;FALOLA Akinola;HE Yunliang;WANG Xuezhong(Beijing Key Laboratory of Enze Biomass and Fine Chemicals,College of New Materials and Chemical Engineering,Beijing Institute of Petrochemical Technology,Beijing 102617,China;School of Chemistry and Chemical Engineering,South China University of Technology,Guangzhou 510640,Guangdong,China)

机构地区：[1]北京石油化工学院新材料与化工学院,恩泽生物质精细化工北京市重点实验室,北京102617 [2]华南理工大学化学与化工学院,广东广州510640

出　　处：《化工进展》2021年第10期5699-5707,共9页Chemical Industry and Engineering Progress

基　　金：国家自然科学基金重点项目(61633006);广东省应用型科技研发资金项目(2015B020232007);广东省自然科学基金(2017A030310262);广东省自然科学基金面上项目(2018A030313263);北京石油化工学院恩泽生物质精细化工北京市重点实验室开放课题(20201001)。

摘　　要：低溶出速率和溶解度严重影响其生物利用度和药效,是造成药物研发候选化合物不能成药的首要因素。近年的研究发现,当颗粒粒径减小到100~200nm,其溶出速率和溶解度会出现显著提升。本文研究了利用湿法纳米研磨技术制备铝碳酸镁药物纳米晶体的工艺。铝碳酸镁是治疗胃病的有效药物,其纳米颗粒悬浮液抗酸效果更好,起效速度更快。本文选择了六偏磷酸钠为分散剂,利用湿法研磨机,考察了分散剂用量、研磨转速、铝碳酸镁含量、研磨时间等参数对颗粒粒度分布的影响规律,获得了在最佳的工艺操作条件为研磨转速3000r/min、研磨时间105min、主药体积分数2%、分散剂为固含量质量分数的1.5%时,成功得到粒径D_(10)(76.4nm)、D_(50)(161nm)、D_(90)(352nm)的铝碳酸镁纳米悬浮液。制酸力实验结果证明纳米铝碳酸镁悬浮液比微米级悬浮液在盐酸中的溶出速率快5倍以上。Low dissolution rate and solubility severely affects their bioavailability and efficacy and is the main factor that led to failure in the development of candidate drug compounds.Recent studies revealed that when the particle size is reduced to around 100-200nm,its dissolution rate and solubility significantly increase.Hydrotalcite is an effective API(active pharmaceutical ingredient)for treating gastric diseases.Its nanoparticle suspension shows a better anti-acid effect and a faster onset of action.In this study,preparation of hydrotalcite nanocrystals using wet nano milling technology was investigated.In the process,sodium hexametaphosphate was selected as a dispersant,and the impacts of dispersant dosage,grinding speed,hydrotalcite content,as well as grinding time on the particle size distribution were examined.An operational envelope was unveiled to obtain a hydrotalcite nano-suspension with D_(10)(76.4nm),D_(50)(161nm),and D_(90)(352nm)with the grinding speed being 3000r/min,the grinding time 105 minutes,the main drug volume fraction 2%,and the dispersant being 1.5%of the solid content mass fraction.The acid-neutralizing capacity experimental result showed that the dissolution rate of the nano-hydrotalcite suspension in hydrochloric acid was 5 times faster than that of the micron-sized suspension.

关 键 词：纳米药物 湿法纳米研磨 铝碳酸镁 制酸力 晶体 

分 类 号：R943[医药卫生—药剂学]