一种批量制备药物共晶的新方法——高速气流法  

High-speed air-blowing impacting method—a renovated method for batch preparation of pharmaceutical co-crystals

作　　者：孙炳扬 彭汝芳[1] 梁华[1] 楚士晋[1] 左金[2] 路波[2] 

机构地区：[1]西南科技大学四川省非金属复合与功能材料重点实验室--省部共建国家重点实验室培育基地,四川绵阳621010 [2]中国空气动力研究与发展中心高速所,四川绵阳621010

出　　处：《安全与环境学报》2017年第3期1081-1087,共7页Journal of Safety and Environment

基　　金：国家自然科学基金国家重大仪器设备专项(51327804)

摘　　要：药物共晶能改善药物物理化学特性、提高药效,机械化学合成法作为一种高效、绿色的合成法在药物共晶合成中得到了广泛应用。首次应用与传统机械法不同的高速气流对撞法批量制备了4种茶碱药物共晶(每种290~320 g),并采用红外光谱(FT-IR)、X射线衍射(XRD)、差热分析(DTA)、扫描电子显微镜(SEM)对4种药物共晶进行了表征。此外,测定了药物共晶的溶解度,结果表明,4种药物共晶在30℃磷酸盐缓冲溶液(pH=7.4)中的溶解度较茶碱显著提高。The paper is aimed at introducing a renovated method we have developed for batch preparation of pharmaceutical cocrystals.The so-called air-flow impacting method is referred to as a continuous synthesis process of the four theophylline pharmaceutical co-crystals,that is,the theophylline-cinnamic acid,theophylline-salicylic acid,theophylline-glutaric acid and the theophylline-benzoic acid.The above said four theophylline pharmaceutical co-crystals have usually been prepared in the following steps：First of all,it is necessary to mix the theophylline（THL）and salicylic acid（SAA）,the glutaric acid（GLA）,cinnamic acid（CA）,benzoic acid（BA）in a molar ratio between 1 to 1.And,then,the mixture can be transferred into an impacting chamber at a rate of 1.5 kg/min（90 kg/h）.In so doing,it is also necessary to accelerate the materials to a very high velocity（300 m/s）in the compressed air（1.5 MPa）,and,next,the intermediate materials can be collected through a short-time reaction（an interval of about 30 seconds）.Afterwards,the AS-prepared four pharmaceutical co-crystals can be examined and characterized by using Fourier transform infrared（FT-IR）spectrometry,X-ray diffraction（XRD）,the differential thermal analysis（DTA）and the electronic scanning microscopy（ESM）.The DTA testing results help to find in nice correlation between the co-crystal melting temperature and the melting points of the corresponding pure theophylline.Furthermore,we have also measured the solubility curves of the four pharmaceutical co-crystals in phosphate buffer of p H 7.4（Na2HPO4＋KH2PO4）at the temperature of 30℃.Thus,the absorbance of a known concentration of the theophylline can be worked out at the givenλmax（270 nm）by using a UV-1800 spectrophotometer,with the absorbance values being plotted against a series of standard solutions in preparing the calibration curve of concentration vs.intensity.What is more,in order to determine the equilibrium solubility,it is also necessary to add an excess

关 键 词：环境工程学 气流对撞法 药物共晶 茶碱 溶解度 

分 类 号：X383[环境科学与工程—环境工程]