利多卡因结晶工艺改进

目的:探索利多卡因的结晶方法,建立适合利多卡因大生产的结晶工艺.方法:通过对降温速率、终点温度的筛选优化了利多卡因的结晶工艺,确定了最佳析晶条件.结果与结论:显微镜观察结果显示,在降温速率为0.2℃/min时,产品晶型稳定为棒状结晶,晶体均匀;X-射线粉末衍射图存在微量差异,说明不同降温速率时的晶型无显著差异.     

晶化温度对SiO2-Al2O3-MgO-F系微晶玻璃析晶的影响

为研究晶化温度对SiO2-Al2O3-MgO-F系云母微晶玻璃的析晶特征的影响,将制得的基础玻璃在不同晶化温度下进行热处理。采用x射线衍射(XRD)、扫描电子显微镜(SEM)分别对样品进行晶体组成分析和组织形貌观察。结果表明:玻璃中析出的晶体主要是云母、柱晶石、莫来石和ZrO2晶体。在晶化温度为730℃时,玻璃样品中只析出粒状ZrO2晶体;在晶化温度为790℃时,玻璃中出现很多分相区域,分相促进棒状晶体和花形晶体析出;在晶化温度为870℃时,云母晶体开始析出,莫来石和柱晶石晶体为主晶相;在晶化温度为950℃时,玻璃中主晶相变为云母晶体;在晶化温度为1030℃时,片状云母晶体定向排列。     

不同温度和冷却速率下高温灰渣的结晶行为

采用单热电偶在线观察系统（SHTT）、图像分析程序等研究等温过程中温度和连续冷却过程中冷却速率对于人工配制灰渣结晶行为的影响,通过计算结晶动力学参数分析其析晶机理,并采用FactSage软件预测晶体类型。实验结果表明,等温过程中,温度降低,结晶所需时间先减小后增大,晶体尺寸减小,结晶比例先增大再稳定最后减小,不同温度区间生成晶体类型不同,导致结晶比例在某些温度出现较大的变化。连续冷却过程中,冷却速率增大,初始结晶温度降低,晶体由块状向颗粒状转变,结晶比例先稳定后减小,由于析出的晶体类型不同,结晶比例出现多个稳定区间,达到临界冷却速率后熔渣全部凝固为玻璃态,无晶体析出。由DSC得到的熔渣结晶放热曲线与SHTT得到的结果吻合较好。     

不同温度和冷却速率下高温灰渣的结晶行为

采用单热电偶在线观察系统(SHTT)、图像分析程序等研究等温过程中温度和连续冷却过程中冷却速率对于人工配制灰渣结晶行为的影响,通过计算结晶动力学参数分析其析晶机理,并采用Fact Sage软件预测晶体类型。实验结果表明,等温过程中,温度降低,结晶所需时间先减小后增大,晶体尺寸减小,结晶比例先增大再稳定最后减小,不同温度区间生成晶体类型不同,导致结晶比例在某些温度出现较大的变化。连续冷却过程中,冷却速率增大,初始结晶温度降低,晶体由块状向颗粒状转变,结晶比例先稳定后减小,由于析出的晶体类型不同,结晶比例出现多个稳定区间,达到临界冷却速率后熔渣全部凝固为玻璃态,无晶体析出。由DSC得到的熔渣结晶放热曲线与SHTT得到的结果吻合较好。     

反应-萃取-结晶过程制备碳酸钙的晶型转变与结晶机理

氨碱法制碱过程中产生的大量蒸氨废液制约了纯碱工业的发展。本文对反应-萃取-结晶耦合工艺产物碳酸钙的晶型转变和结晶机理进行了研究。结果表明,在此耦合过程中,二氧化碳优先被有机相吸收,然后传递到水相进行反应,首先生成的是碳酸氢钙,之后迅速分解为无定形碳酸钙。温度对碳酸钙晶型影响显著,温度较高时,无定形碳酸钙优先转变为针状文石;温度较低时,无定形碳酸钙优先转变为球状球霰石。随后文石和球霰石均会通过溶解-重结晶作用逐渐转变为稳定的菱形方解石。常温下,反应过程中同时进行着新的球霰石的生成和球霰石转变为方解石两个过程,参与反应的二氧化碳浓度越高,晶体中球霰石的含量越高。     

卡马西平多晶型结晶工艺研究

通过生物显微镜、X射线粉末衍射(XRD)、马尔文粒度分析仪,差热分析(DSC)及在线聚焦反射测量仪(FBRM)和粒子成像测量仪(PVM)研究了在卡马西平结晶过程中各种操作参数对产品质量特别是晶型的影响,具体考察了溶剂、晶种、结晶方式、干燥、温度、搅拌速率及冷却速率对晶体产品质量的影响。结果表明,不同溶剂中缓慢结晶,高介电常数溶剂(如醇类)中得到卡马西平晶型Ⅲ,乙醇-水混合物中当乙醇摩尔分数低于40%时结晶产物为二水物,四氢呋喃中结晶得到晶型Ⅱ,其他溶剂得到产品为混合晶型;对于醇类溶剂,蒸发结晶一般得到卡马西平晶型Ⅱ,而缓慢冷却得晶型Ⅲ;以正丙醇为溶剂,加大量颗粒较小的晶种可以得到粒度较均一的产品;晶型Ⅱ产品由于特殊的结构,易于有结晶用溶剂包藏在晶体中,加热到约140℃溶剂逸出;温度是影响晶型的重要因素,在较高温度区间(90~76℃)结晶得晶型Ⅱ,而在低温度区间(52~20℃)得晶型Ⅲ;搅拌速率在较低的温度下对晶型没有影响,搅拌速率大可以避免晶体的聚集,形成较均匀的颗粒;3种降温速率结果显示,产品均为卡马西平晶型Ⅲ,但先慢后快的降温速率可以得到更均匀的颗粒晶体。     

熔盐法合成钨酸锌纳米晶及花朵状氧化锌

采用熔盐法成功制备出了钨酸锌(ZnWO4)纳米晶.用XRD、SEM分别对产物的相组成、粒度、显微结构等进行了表征.结果表明:以Na2WO4·2H2O、Zn(NO3)2·6H2O为原料,NaNO3-LiNO3为熔盐,分别在200～400℃保温12h均能合成纯相的ZnWO4粉体;当温度达到500℃时生成花朵状的ZnO片状粉体;ZnWO4颗粒的形貌与煅烧温度和保温时间有密切关系,随温度升高,颗粒形貌的演变过程为:当温度为200℃时生成纳米颗粒;升高温度至300℃时,生成棒状纳米晶体;继续升高温度到400℃时,形成了块状的微米晶体.随着保温时间的延长,颗粒形貌的演变过程为:由纳米颗粒转变为棒状纳米晶体.     

奥托金的性质及其在火箭固体推进剂中的应用

本文综述了奥托金的性质及单元推进剂性能,並根据其性质论述了它在固体火箭推进剂的应用领域及奥托金推进剂的技术问题。奥托金,学名环四次甲基四硝胺,其结构式为它是一种耐热炸药,可在火箭固体推进剂中作为氧化剂使用。关于这方面已有少数综述性的资料发表。本文综述奥托金应用于火箭固体推进剂的有关性质及技术问题。一、奥托金的性质奥托金是一种白色晶体,一般认为它有四种晶型,常见的为稳定的β单斜晶体,常温至156℃是稳定的。其他三种是亚稳定的α斜方晶体、γ单斜晶体和不稳定的δ单斜晶体。各种晶型能互相转变,並伴随发生体积和热量的变化。随着温度的升高,四种晶型的稳定次序     

高温固相法制备片状α-Al_2O_3粉体

以氟化铝作为烧结助剂,采用高温固相法制备片状α-Al_2O_3。研究了烧成温度、保温时间、氟化铝添加量对氧化铝晶型和形貌的影响。研究结果表明,当氟化铝添加量为10wt%时,不稳定晶型的氧化铝在900℃下完全转变为稳定的α-Al_2O_3,氟化铝可以显著降低氧化铝的晶型转变温度;随着氟化铝添加量的增多,氧化铝的形貌由絮凝状变为蠕虫状最终变成片状形貌。烧成温度1200℃、保温时间3 h、氟化铝添加量20wt%条件下,可以得到大而薄的片状氧化铝,但形貌比较不规则。     

温度和添加剂对Ca(HCO3)2分解制备CaCO3的影响

在碳酸氢钙(Ca(HCO3)2)的分解过程中,通过温度和聚乙二醇(PEG)成功地控制了碳酸钙(CaCO3)的晶型和形貌.用XRD和SEM对制得的CaCO3的晶体类型和颗粒形貌进行表征,结果显示在不添加PEG的情况下,可以观察到菱面体方解石、层状球霰石、棒状及针状的文石.在所有样品中主晶相都是方解石,其含量随温度升高而增多,而球霰石和文石则随温度升高而减少.考察了分解温度为80℃时,添加不同分子量的PEG对CaCO3的晶体类型和颗粒形貌的影响.当反应体系中加入PEG-2000时,方解石仍是主要的晶型,但含量明显减少,文石相增加到39.2％;而加入PEG-6000时,方解石相明显减少,文石相增加到79.3％.这些结果表明:在Ca(HCO3)2的分解过程中,温度和PEG可以调控CaCO3的晶型和形貌.     

Stretch-induced bidirectional polymorphic transformation of crystals in poly(butylene adipate)

Stretch-induced structural changes of poly(butylene adipate) at various temperatures were systematically investigated by X-ray diffraction method. It was found that tensile deformation could lead to both occurrence of α to β and β to α crystal transition via solid–solid process. Experimental results shows that either α or β form can be adopted as the stable phase for PBA crystal depending on the competition between tensile strain and temperature. Higher temperature favors β to α crystal transformation, while larger strain would result in α to β crystal transformation. Due to the conversion of crystal stability during stretching, a unique “β to α to β” transformation phenomenon of PBA appears at appropriate temperature for original β spline. This study provides evidence that both temperature and tensile strain can alter the relative stability of polymorphic crystals of semi-crystalline polymers.     

液滴-微流体环境下L-谷氨酸的多晶型现象

利用液滴-微流体法研究了温度、液滴大小及溶剂组成对L-谷氨酸晶型的影响,并利用显微镜和PXRD进行了表征。研究结果表明,相同过饱和度下,温度越高越有利于亚稳态晶型的生成;反之,有利于稳态晶型的生成。相同过饱和度和温度下,液滴大小对晶型没有影响。溶剂中乙醇含量的增加有利于亚稳态晶型的生成。     

Effects of mixing,seeding, material of baffles and final temperature on solution crystallization of l-glutamic acid in an oscillatory baffled crystallizer

In this paper, we report the effects of mixing intensity, seeding, composition of baffle material and final temperature on meta-stable zone width (MSZW) and crystal polymorph in solution crystallization of an industrially important compound, l-glutamic acid, in an oscillatory baffled crystallizer (OBC). The results show that the MSZW decreases with increasing of mixing; meta-stable α crystals are transformed into stable β crystals with enhanced mixing intensity. Seeding meta-stable α crystals in operational conditions that promote β crystals leads to the formation of α crystals allowing co-existence of both forms; while seeding stable β crystals in conditions that favour α form allow β crystals prevailing in all conditions. Smoother surface of baffle material in OBC exhibits larger MSZW and favours meta-stable crystals, while rougher surface has smaller MSZW with stable crystals dominating. The meta-stable crystals gradually change into the stable form when final cooling temperature is closer to its nucleation temperature. The outcomes from this work indicate that by controlling process parameters desirable crystal polymorph can be obtained in the OBC.     

THE USE OF LOCAL THERMODYNAMIC PATH FOR QUALITY PROBLEMS DURING CONVECTIVE DRYING

The pharmaceutical drug under investigation in this paper has two hydration states with several polymorphic forms. The two hydration states are tetrahydrate and monohydrate. Two polymorphs of monohydrate are in competition. Process must lead to the metastable therapeutic form (TF) although the non therapeutic form (NTF) is the stable one. The sensitive stage is drying

From desorption isotherms coupled with infrared spectroscopy, an equilibrium diagram of the different forms versus the external conditions (temperature and relative humidity) is performed. A macroscopic study achieved on tangential convective drying shows that the equilibrium diagram does not insure to obtain the metastable form after drying. It is deduced from an experimental analysis of internal temperature and water activity that the final form depends on the local thermodynamic path. Indeed, if NTF favourable conditions occur within the product during the process, this irreversible form remains although the final form predicted by the diagram is TF

It is concluded that NTF is promoted by a slowing down of transfers and an enhanced water vapour removing (greater exchange surface).     

奥拉帕利多晶型及晶型转化研究

奥拉帕利是全球首个上市的聚腺苷二磷酸-核糖聚合酶抑制剂。研究了奥拉帕利形成异质同晶溶剂化物的现象的机理，并进一步通过四氢呋喃溶剂化物单晶解析了奥拉帕利异质同晶溶剂化物的类型为独立位点型；研究了奥拉帕尼无水晶型A/L热力学稳定关系，分析了溶剂介导下稳定晶型向介稳晶型异常转变的可能原因；同时考察了温度和水体积比对无水晶型A与水合物晶型H相变过程的影响。     

THE USE OF LOCAL THERMODYNAMIC PATH FOR QUALITY PROBLEMS DURING CONVECTIVE DRYING

ABSTRACT

The pharmaceutical drug under investigation in this paper has two hydration states with several polymorphic forms. The two hydration states are tetrahydrate and monohydrate. Two polymorphs of monohydrate are in competition. Process must lead to the metastable therapeutic form (TF) although the non therapeutic form (NTF) is the stable one. The sensitive stage is drying

From desorption isotherms coupled with infrared spectroscopy, an equilibrium diagram of the different forms versus the external conditions (temperature and relative humidity) is performed. A macroscopic study achieved on tangential convective drying shows that the equilibrium diagram does not insure to obtain the metastable form after drying. It is deduced from an experimental analysis of internal temperature and water activity that the final form depends on the local thermodynamic path. Indeed, if NTF favourable conditions occur within the product during the process, this irreversible form remains although the final form predicted by the diagram is TF

It is concluded that NTF is promoted by a slowing down of transfers and an enhanced water vapour removing (greater exchange surface).     

氨基酸调控无水碳酸镁晶体结晶试验研究

无水碳酸镁晶体作为一种新型无机功能材料引起了研究者们的广泛关注。以氯化镁为原料,碳酸钠为沉淀剂,合成了无水碳酸镁晶体,再以甘氨酸、组氨酸、丙氨酸及L-天门冬氨酸四种不同种类氨基酸作为添加剂,调控其结晶的粒度及形貌。采用X射线衍射仪、扫描电子显微镜、激光粒度分析仪对合成产物进行表征,分析不同种类氨基酸对合成的无水碳酸镁晶体物相结构和形貌的影响。结果表明:在组氨酸调控下合成的无水碳酸镁结晶纯度高,生成的产物中n(Mg²⁺)∶n(CO^2-₃)为1∶0.94;L-天门冬氨酸调控合成的晶体纯度次之;甘氨酸和丙氨酸调控合成的晶体中掺杂大量碱式碳酸镁晶体。在组氨酸、L-天门冬氨酸、甘氨酸及丙氨酸四种氨基酸调控作用下,晶体结晶形貌依次呈凸面球三角形状、近球状、球状及不规则状,且无水碳酸镁晶体粒径分布均呈先上升后振荡下降最后小粒径拖尾的趋势。以上研究结果为无水碳酸镁晶体的仿生合成提供了参考。     

溶剂对FOX-7晶体相变和热性能的影响

采用重结晶法在二甲基甲酰胺(DMF)/H2O、二甲基亚砜(DMS)O/H2O和N-甲基吡咯烷酮(NMP)/H2O等不同溶剂体系中得到FOX-7晶体,用扫描电子显微镜(SEM)测试晶体的形貌、变温X-射线粉末衍射(XRD)分析晶型和相变、差示扫描量热仪(DSC)测试其热性能。结果表明,不同溶剂重结晶得到的FOX-7晶体形貌有较大差别,在DMSO/H2O溶剂中得到的晶体质量要优于其他两种;3种溶剂中得到FOX-7晶体的晶型和相变过程相同,即常温下FOX-7的晶型为α晶型,在120℃时,FOX-7完成α→β相变,至185℃时,完成β→γ相变;重结晶的FOX-7晶体5s爆发点温度提高了4~9℃,说明热稳定性增强。     

几种多态含能材料构型转变的DFT研究

为了从分子层面上对含能材料不同分子构型间的转变情况有一个直观认识,借助Gaussian 09软件,运用密度泛函理论(DFT),采用TS算法搜寻β-RDX→α-RDX、γ-HMX→β-HMX、ε-CL-20→β-CL-20及β-FOX-7→α-FOX-7在分子构型转变过程中的过渡态结构,确定了它们的构型转变过程;并通过计算吉布斯自由能随构型转变路径的变化,比较多态含能材料分子构型转变的难易程度。结果表明,由亚稳晶型到稳定晶型的转变首先会越过过渡态,克服自由能能垒转变为亚稳态结构,实现β-RDX→α-RDX、γ-HMX→β-HMX、ε-CL-20→β-CL-20及β-FOX-7→α-FOX-7分子构型转变分别需要克服的自由能能垒分别为5.25、22.21、9.69和10.24kJ/mol。因此,常温常压下β-RDX→α-RDX、γ-HMX→β-HMX、ε-CL-20→β-CL-20及β-FOX-7→α-FOX-7构型转变的难度大小排序为:HMX>>FOX-7>CL-20>RDX。     

Crystallization behavior and polymorphism of poly(1,4‐butylene adipate): Effect of anhydrous orotic acid as nucleating agent

The effect of anhydrous orotic acid (OA), as a biocompatible nucleating agent (NA), on the non‐isothermal and isothermal crystallization behaviors, polymorphic crystalline structure and phase transition of poly(1,4‐butylene adipate) (PBA) was investigated. It is found that the OA increased the crystallization temperature of the PBA in the non‐isothermal crystallization process and decreased the crystallization time of the PBA in the isothermal crystallization process. Meanwhile, the spherulite size decreased and spherulite density increased for the PBA. The OA favored the formation of the PBA α‐form crystal, compared to the neat PBA. In addition, upon incorporation of the OA, the β‐to‐α phase transition rate was enhanced significantly. Mechanisms for the preferential formation of the PBA α‐form crystal and the accelerated phase transition have also been proposed. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42957.