Effects of Solvent and Impurity on Crystal Habit Modification of 11α-Hydroxy-16α,17α-epoxyprogesterone

The effects of solvent and impurity on the crystal habit of 11α-hydroxy-16α,17α-epoxyprogesterone (HEP)grown from solution were studied by scanning electron microscope.Long prismatic crystals were produced when HEP was crystallized from pure acetone and N,N-dimethylformamide,while blocky crystals were produced from pure chloroform by cooling crystallization.One kind of isomorphic impurity,16α,17α-epoxyprogesterone(EP) was selected to examine its effect on the HEP crystal habit.When the content of EP in the mother liquor is very high(55.45%,solvent free basis),the habit of produced HEP crystals was greatly modified from prismatic to octa-hedral.The differential scanning calorimetry and X-ray powder diffraction analyses showed that the change of crystal habit was originated from the crystal structure modification.

Hydrothermal preparation and crystal habit of X-zeolite powder

The preparation of X-zeolite powder was investigated in hydrothermal system, the crystal growth process of X-zeolite in hydrothermal condition was characterized by means of X-ray diffraction, scanning electron microscope and infrared ray. The results show that X-zeolite powder with uniform granularity and intact crystal shape can be obtained in hydrothermal system of acid-treated stellerite KG-*5CD*2KG-*9NaOHKG-*5CD*2KG-*9NaAl（OH）4KG-*5CD*2KG-*9H2O; the crystallite size is in the range of 2CD*23μm. The best reaction time of hydrothermal preparation is 6h. The formation phases of X-zeolite crystal are as follows: dissolution of feedstocks → formation of [SiO4] 4- and [AlO4] 5- tetrahedron, many-membered ring, β cage → formation of crystal nucleus and nano-particle → aggregation growth of nano-particle → coalescence growth of crystallite. The crystal habits of X-zeolite are intimately related with crystallization orientation of β cage in crystal and with its coupling stability on every crystal face family.

Ultrasound assisted crystallization of cephalexin monohydrate:Nucleation mechanism and crystal habit control

With the high-quality requirements for cephalexin monohydrate,developing a robust and practical crystallization process to produce cephalexin monohydrate with good crystal habit,appropriate aspect ratio and high bulk density as well as suitable flowability is urgently needed.This research has explored the influence of ultrasound on crystallization of cephalexin monohydrate in terms of nucleation mechanism and crystal habit control.The results of metastable zone width and induction time measurement showed the presence of ultrasound irradiation can narrow the metastable zone and shorten induction time.Cavitation phenomena generated by ultrasound were used to qualitatively explain the mechanism of ultrasound promoting nucleation of cephalexin monohydrate.Furthermore,on the basis of classical nucleation theory and induction time data,a series of nucleation-related parameters(such as crystalliquid interfacial tension,radius of the critical nucleus and etc.)were calculated and showed a decreasing trend under ultrasound irradiation.The diffusion coefficient of the studied system was also determined to increase by 72.73%under ultrasound.The changes in these parameters have quantitatively confirmed the mechanism of ultrasound influence on the nucleation process.In further,the calculated surface entropy factor has confirmed that the growth of cephalexin monohydrate follows continuous growth mechanism under the research conditions of this work.Through the exploration of crystallization conditions,it is found that suitable ultrasonic treatment,seeding,supersaturation control and removal of fine crystals are conducive to improving the quality of cephalexin monohydrate product.Optimizing the crystallization process coupled continuous ultrasound irradiation with fine-crystal dissolution policy has achieved the controllable production of monodisperse cephalexin monohydrate crystal with good performance.

Crystal habit for upconversion laser crystal of BaY_2F_8

BaY2F8 crystals had a relatively low symmetry, and its XRD data showed that those strong diffractions occured in a narrow angle range, so it was difficult to orientate the single crystals of BaYEFs. In this paper, based on the structure characteristics and XRD data, the crystal habit of BaY2F8 was analyzed. The strong bond in crystal structure of BaYEF8 was Y-FE-Y, which stretched to the shape of chain along the direction of [001]. And this was an advantaged direction for the crystal growth. The steady shapes of BaY2F8 were composed of rhombic prism { 130} and {021 }. The crystal showed an axial habit in the direction of [001]. The analysis of the crystal slice obtained by temperature gradient technique verified the above conclusion. The BaY2F8 crystal was grown by compulsive methods such as Czochralski method.

Controlling solid form and crystal habit of triphenylmethanol by antisolvent crystallization in a microfluidic device

Crystal habit and crystal form are critical elements in determining product properties and functions. In this work, we developed a microfluidic antisolvent crystallization technique to rapidly screen and accurately control the solid form and crystal habit of triphenylmethanol(Ph_(3)COH). This advanced technique separates the primary mixing of solutions from crystal formation(nucleation and growth) by introducing the microfluidic device, avoiding clogging in microchannels to obtain high-quality crystals. The results show that we can achieve controllable preparation of pure 2Ph_(3)COH·DMSO(DMSO solvate), pure Ph_(3)COH(form β), and mixed crystals with different mass ratios. Moreover, the microscale can prompt the DMSO solvate to grow into hexagonal sheet-like and bulk crystals. We can regulate the aspect ratio of hexagonal sheet-like crystals in binary solvents and control the crystal habit of the form β to transition between long needle-like shapes and short hexagonal prisms in DMF-H_(2)O. Meanwhile, we revealed that the solvent ratio, the antisolvent flow rate, and the initial concentration of Ph_(3)COH are the main factors affecting the solid form selectivity and morphology transition. Such a novel method would be considered as a promising technique to be extended to screen and control key crystallization parameters of other substances.

Effect of Mixed Solvents and Additives on the Habit Modification of 6-APA Crystals

6-aminopenicillanic acid (6-APA) crystals obtained under different physical and chemical conditions of the solutions may present different habits. The habits of diamond-shaped plates are desirable compared with other habits of 6-APA crystals. To obtain ideal 6-APA crystals, the effects of the mixed solvents and additives on 6-APA crystal habits were investigated. Ethanol or acetone was used as the organic solvent, and impurities existing in the 6-APA purification process were used as the additives. 6-APA growth habits were changed when the concentrations of ethanol, acetone or phenyl acetic acid were increased to exceed their critical concentration. The observed results show that the dominant face on 6-APA crystals was identified to be {020}, but the overall habit was controlled by the relative growth rates of the {101} and {002} faces. Crystal growth rates and habits can be appreciably changed by specific adsorption of additives on crystal faces.In some cases solvent molecules can act in a similar way and may be regarded as bulk additives. The effects of additives and organic solvents on 6-APA crystal habits were the results of adsorption effect, which fitted the experimental results quite well.

Influences of additives on the crystal habit of potassium chloride

By means of constant control speed cooling crystallization,the influences of four additives,including lead chloride,cadmium chloride,sodium salicylate,and quaternary ammonium salt,on the crystal habit of KCl were investigated.The results show that the crystal habit of KCl is cube without additives,the crystal habit of KCl is ellipsoid-like in the presence of Pb^(2+),the crystal habit of KCl is strip in the presence of Cd^(2+),and the crystal habit of KCl is cavate cube in the presence of sodium salicylate.Xray diffractometry analysis reveals that these additives can change the crystal habit of KCl but not its crystal structure.

X-ray Multiple Diffraction Topographic Imaging Technique For Growth History Study of Habit Modifying Impurity Doped Crystals

A novel crystal characterization instrument has been built up in which a combination of X-ray multiple diffraction and X-ray topography is applied to enabling the cross-correlation between micro-crystallographic symmetry and its spatial dependence in relation to lattice defects. This facility is used to examine, in a self-consistent manner, growth sector-dependant changes to both the crystallographic structure and the lattice defects associated with the action of habit-modifying additives in a number of representative crystal growth systems. In addition, the new instrument can be used to probe micro-crystallographic aspects(such as distortion to crystal symmetry) and relate these in a spatially resolved manner to the crystal defect structure in crystals doped with known habit modifiers.

注射用亚胺培南西司他丁钠质量分析

目的 对国内市场中不同企业的注射用亚胺培南西司他丁钠的质量状况进行评价,发现质量风险点,为仿制药一致性评价提供质量控制关键点。方法 采用法定检验结合探索性研究的方法对样品进行检验,统计分析注射用亚胺培南西司他丁钠的整体质量水平,分析不同企业产品的差异。结果 按法定标准检验,80批次抽验样品结果均符合规定。但发现原研产品的复溶时间更快;不同企业的产品有关物质和含量结果差异较大;现行质量标准差异较大亟待提高统一。探索性研究表明,样品复溶时间与制剂中亚胺培南晶癖及粒度相关;采用LC/MS等方法对本品有关物质的来源进行了归属,对部分杂质结构进行了推断;对本品的含量测定方法进行了优化。结论 国内市场中注射用亚胺培南西司他丁钠的质量总体较好;在开展仿制药一致性评价工作中,需关注亚胺培南的晶癖以及制剂的有关物质、含量、充氮工艺和异亚丙基丙酮等质量关键点;现行标准有待统一和提高。

Optimizing the Aspect Ratio of Cephalexin in Reactive Crystallization by Controlling Supersaturation and Seeding Policy

Batch crystallization in acidic aqueous solution of cephalexin was conducted by reactive crystallization with or without seeding. Supersaturation was generated by mixing ammonia and acidic aqueous solution of cephalexin and controlled by solution feeding rate and seeding conditions. UV and Morphologi G3 were used to measure supersaturation and aspect ratio. Experimental results demonstrated that burst nucleation occurred and the products were needle-like at high supersaturation;meanwhile, the products were plate-like and had high aspect ratio at low supersaturation. Analysis of the measured supersaturation profi les and corresponding aspect ratio explained the mechanisms governing the aspect ratio. The optimized operating parameters were also proposed (seeding supersaturation is equal to 1.3, seed mass ratio 8% and feeding rate 368 μL/min).

Growth Habit of the Basic Oxysulfate Magnesium Whisker

The growth habit of the basic magnesium oxysulfate whisker was investigated based on the theoreticalmodelof anion coordination polyhedron growth units.It is found that typicalbasic magnesium oxysulfate whisker growth is consistent with anion tetrahedralcoordination incorporation rules.The growth units of basic magnesium oxysulfate whiskers are [Mg-（OH）_4]^（2-） and HSO_4^-.[Mg-（OH）_4]^（2-） is the favorable growth unit and whisker growth is in the direction of the [Mg-（OH）_4]^（2-） combination.A plurality of [Mg-（OH）_4]^（2-） s combine and become a larger dimensionalgrowth unit in a one-dimensionaldirection.Then HSO_4^- and larger dimensionalgrowth units connect as basic magnesium sulfate whiskers,according to the structuralcharacteristics of the basic magnesium sulfate whisker,which can guide the synthesis of magnesium hydroxide whisker.

Heterogeneous crystallization of Chlorzoxazone for modulating the physicochemical properties of crystals Author links open overlay panel

The polymer on modulating the crystal's habit is an evolving research in pharmaceutical crystallization.This study demonstrates the crystal habit modification of chlorzoxazone(CHZ)by heterogeneous crystallization(HC)in the binary solvent acetonitrile-ethanol(A-E(1:1))in the presence of polyvinylpyrrolidine(PVP)at concentrations of 0.50,0.75,and 1.00 wt%.The A-E(1:1)and PVP in HC experiments influenced to change the shape of crystals from needle to plate shape and reduced the crystal size producing a lower aspect ratio(in the range of 1.5-2.3).In the presence of PVP,the CHZ size distribution is 65-78μm which tends to enhance the powder flow-ability of CHZ crystals and as the PVP concentration increases,the nucleation rate decreases.The solubility of size-reduced CHZ crystals at different pH is found to be improved by 1.2-1.4 times.Hence,HC is deemed effective in modifying the physicochemical attributes of CHZ.

Mg^(2+) 对半水硫酸钙晶须结晶习性的影响

本文以磷石膏为原料蒸压制备半水硫酸钙晶须,采用数字显微镜、X射线衍射(XRD)和X射线光电子能谱(XPS)等微观测试方法对Mg^(2+)作用下的半水硫酸钙晶须微观形貌、组成及晶面发育情况等进行试验研究,运用分子动力学技术模拟计算Mg^(2+)在半水硫酸钙晶体晶面的相互作用能和径向分布函数,两者结合探讨Mg^(2+)对半水硫酸钙晶体不同晶面结晶习性的影响。结果表明,Mg^(2+)和半水硫酸钙晶体不同晶面的相互作用能从小到大顺序为:ΔE_((200))<ΔE_((002))<ΔE_((400))<ΔE_((020))<ΔE_((204))即Mg^(2+)主要吸附在半水硫酸钙晶体的(200)、(002)、(400)晶面上。Mg^(2+)与SO^(2-)_(4)间的作用距离小于Ca^(2+)与SO^(2-)_(4)间的作用距离,Mg与S之间产生了明显的电子效应,且电子效应随硫酸镁掺量的增加而增强,XRD衍射峰位置随硫酸镁掺量的增多向右偏移变得更加明显,说明有少量的Mg^(2+)嵌入半水硫酸钙晶格。在硫酸镁掺量0.15%(质量分数,下同)时,优先促进晶体c轴方向的生长,使半水硫酸钙晶须呈细长针状,平均长度为47.29μm,平均长径比为36.07;在硫酸镁掺量为0.30%时,抑制晶体沿c轴和径向的生长,使半水硫酸钙晶须呈细短针状,平均长度为39.72μm,平均长径比为28.91。

头孢他啶双股进料结晶工艺的研究

针对头孢他啶结晶产品聚结、晶习差、粒度分布不均匀等问题,设计了双股进料结晶工艺,并将结晶环境控制在介稳区,有效避免自发成核,操作简单,容易控制。采用单因素法研究了结晶液初始浓度、料液流加速率、搅拌速率、温度以及养晶时间对结晶产品收率、晶习及粒度分布的影响,确定了优化的工艺参数:结晶液初始浓度(溶质质量/溶剂质量)0.33 g·g^(-1),料液流加速率0.14 mL·min^(-1),温度27℃,养晶时间60 min,搅拌速率为250 r·min^(-1)可以得到均匀的片状头孢他啶晶体,晶习完整,中值粒径达到184μm,径距为1.290,收率可以达到80%。

晶习调整剂及晶种对细晶煅烧氧化铝性能的影响

低钠细晶煅烧氧化铝是一种应用广泛的精细氧化铝,开发低钠细晶煅烧氧化铝绿色高效低成本制备技术意义重大。本文研究了预处理对工业氧化铝脱钠效果的影响以及晶习调整剂和晶种对煅烧氧化铝相转化率、氧化钠杂质含量、原晶粒度、研磨性能的影响,研究结果表明:以工业氧化铝为原料,通过原料预处理脱钠提纯,添加晶种异相成核诱导和晶习调整剂可以调控煅烧氧化铝的原晶粒度,提高相转化率,降低氧化钠杂质含量,得到高α相含量、低钠且原晶细小均匀的煅烧氧化铝,开发了回转窑煅烧生产低钠细晶氧化铝技术。

三聚磷酸钠对二水石膏晶体生长习性与晶体形貌的影响

三聚磷酸钠是建筑石膏高效缓凝剂。用扫描电镜和X射线光电子能谱研究了三聚磷酸钠对建筑石膏凝结硬化、液相离子浓度与过饱和度、二水石膏晶体生长习性与形貌的影响。从晶体生长的角度分析了三聚磷酸钠对二水石膏的作用机理。结果表明:三聚磷酸钠显著改变了二水石膏晶体的生长习性,使其由针状变为短柱状或板状,且晶体尺度增加;三聚磷酸钠通过化学作用选择吸附在二水石膏晶体(111)面,抑制其在c轴方向的生长,改变了晶面在不同轴向的相对生长速率,使二水石膏晶体生长习性和形貌发生了改变;三聚磷酸钠使石膏液相离子浓度和过饱和度降低,晶体成核几率和成核速率降低,导致二水石膏晶体粗化。

红霉素溶析结晶过程中原溶剂对其晶习及纯度的影响研究

针对目前我国红霉素产品杂质含量高、外观较差等问题，研究了溶析结晶过程中异丙醇、正丙醇、丙酮、乙醇等原溶剂对红霉素结晶晶习及纯度的影响，实验结果发现丙酮和乙醇的混合溶剂（体积比３∶１）作为原溶剂可较好地改善红霉素晶习并提高其纯度。

有机分子晶体晶习预测的研究进展

本文简要介绍了晶习预测在工业结晶过程中的意义 ;从结晶内部结构出发 ,阐述了晶习预测的基本原理 ,介绍了几种常见的理论模型 ,就上述模型的特点和用途进行了比较 ,并对未来的发展方向做了展望。附带介绍了几种常见的计算软件。

不同类型媒晶剂对硫酸铵晶体形态学指标的影响

选用硫酸铵这一物系,从实验和模拟两个角度研究了在媒晶剂作用下的结晶过程,探讨媒晶剂对晶体产品形态学指标的影响规律。利用粉末衍射仪(XRD)和扫描电镜(SEM)对晶体产品的晶体结构、形态学指标进行了测定与分析。应用分子摸拟软件Materials Studio计算媒晶剂和硫酸铵各个晶面之间的单分子结合能数值,结合能数值与其对晶面生长速率的影响具有良好的对应关系,进而确定了媒晶剂对硫酸铵晶体晶习的影响,结合硫酸铵晶体成核和生长动力学规律,推断出媒晶剂的影响机理。

水热条件下ZnO微晶的结晶习性及其形成机理

研究了ＺｎＯ微晶在不同水热条件下的结晶习性和形貌。实验表明：在中性或弱碱性水热介质中形成的氧化锌晶粒呈长柱状，在强碱性溶液中和高的反应温度下形成的晶粒则呈短柱状和规则多面体颗粒状，而在适度碱性水热条件下，氧化锌晶粒呈明显的极性生长。水热条件对ＺｎＯ微晶的结晶习性和形貌有着很大的影响。从结晶化学角度出发，结合晶体结构、溶液结构和生长时的水热条件，探讨了氧化锌微晶结晶习性的形成，氧化锌晶粒具有明显的极性晶体生长特征；探讨了水热条件与晶粒形态之间的关系，并从这一关系出发在水热条件下制备了氧化锌超细微晶。