限域空间内的结晶研究进展

在经典成核理论基础之上,综述了无机、有机化合物和大分子聚合物等几类物质在不同的限域空间内的结晶行为,并与普通溶液结晶行为进行了比较。分析了不同限域空间对晶体的成核、生长以及相转化产生的影响,如成核速率、生长取向、晶型种类等。研究表明,在高度分散的纳米孔基质中,孔径尺寸、形貌对晶体成核与生长的控制机理不同,从而影响了最终的晶体结构。     

药物多晶型的研究进展

多晶型研究是制药领域的一个研究热点,而多晶型体系的分子组装规律及其控制手段是最为关键的研究内容。介绍了多晶型的分子组装规律,即成核理论（包括经典成核理论以及新兴的二步成核理论）,以及多晶型的调控方法,并重点介绍目前新型的调控手段（如离子液体、模板剂以及微通道技术等）。此外,结合药物晶型转化的实际案例,说明晶型转化技术在药物产品质量调控中的重要作用。     

甘氨酸多晶型的研究进展

综述了近年来甘氨酸各种晶型的制备方法、各晶型的热稳定性、结晶条件对晶型的影响、晶型间的相互转化、结晶新工艺及新晶型等方面的研究。对甘氨酸多晶型的研究,不仅有助于甘氨酸晶型的控制及新晶型的开发,而且可为其它药物晶型的研究提供新的思路和指导。     

农药生产中的工业结晶技术

结晶是农药生产过程中一个重要的环节,对结晶过程的设计、控制和优化将决定农药晶体产品的晶型、纯度以及粒度分布等性能。从农药多晶型、产品粉体性能以及结晶操作方式选择等方面阐述了工业结晶对农药产品质量的影响。创新农药的晶型研究以及连续结晶技术将会成为未来农药研发和生产的重要发展方向。     

红辉沸石两步水热法合成A型分子筛机理研究

以红辉沸石为原料,采用两步水热法将其转化为A型分子筛,系统地探讨A型分子筛的转化机理。对不同晶化时间的样品进行系统表征,深入解析天然红辉沸石转化A型分子筛的成核机制、生长控制、晶型稳定转化等结构基础问题。研究表明,A型分子筛的生长可分为3个阶段：在成核诱导期（晶化时间≤0.5 h）,凝胶中的β笼通过双四元环构筑成α笼,生成较多晶核及少量1 μm小晶体;此后为快速生长期（晶化时间1~4 h）,大量晶核通过聚集生长形成2 μm大晶体;在生长稳定期（晶化时间5~8 h）,通过二次成核凝胶将会转化为更多的分子筛晶体。A型分子筛的形成遵循：铝硅酸盐凝胶→四元环、六元环→双四元环、β笼→α笼的晶化过程,因而其转化过程符合液相转化机理。     

工业结晶技术在维生素生产中的应用

通过详细的文献查阅,主要从药物的晶型和粒度控制、药物制剂以及结晶工艺的选择对维生素产品质量的影响进行阐述。指明新型维生素药物晶型的研发、制剂的功能化、连续结晶技术的应用等是未来研究的方向。     

工业结晶技术在维生素生产中的应用

通过详细的文献查阅,主要从药物的晶型和粒度控制、药物制剂以及结晶工艺的选择对维生素产品质量的影响进行阐述。指明新型维生素药物晶型的研发、制剂的功能化、连续结晶技术的应用等是未来研究的方向。     

离子液体在药物晶体工程中的应用

近年来，使用离子液体替代传统溶剂参与调节结晶过程中的各种相互作用以获得新颖的晶体结构是药物晶体工程的研究前沿。研究人员在离子液体体系中得到了使用传统溶剂无法制得的药物晶型或晶习并进行了相应机理的初步探索。针对离子液体在药物晶体工程中的应用，本文从离子液体的组成和性质及其在药物增溶、药物晶型及晶习的调控和药物共晶及盐的制备几方面展开，首次综述了相关研究成果并基于红外光谱、分子动力学模拟等手段从相互作用的角度对机理进行分析，其中氢键和范德华力相互作用起到了重要影响。最后针对该领域现存的问题如离子液体的选择处于盲筛阶段，相应机理研究缺乏和应用范围不广泛，指出建立系统的离子液体选择标准和深入研究机理是未来的主要研究方向。     

纳米二氧化钛的水热制备及光催化研究进展

纳米二氧化钛具有优异的光催化活性以及光电转化、光致发光特性。纳米二氧化钛的水热法制备具有独特的优势。重点介绍了纳米二氧化钛的3种晶体结构、水热法制备的过程机理,以及反应条件(原料、温度、pH等)对所得产物的影响,反应条件控制得当,可以获得具有一定晶型组成、尺寸和形状的纳米二氧化钛。介绍了纳米二氧化钛的光催化机理、晶体结构对光催化的影响,以及光催化性能的改进。根据光催化机理可以设计制备出具有分散性好、晶粒小、高比表面积、晶型可控的高催化活性的纳米二氧化钛,其在抗菌消毒、污水处理等方面具有很高的应用价值和良好的发展前景。     

云母钛复合材料的制备与光学性能的研究

通过ＸＲＤ，ＳＥＭ，ＥＤＡＸ及反射率等分析，对金红石型ＴｉＯ２包覆云母复合材料的制备及其光学性能进行了研究，着重讨论了复合机理、晶型转化、珠光效应以及色调、反射率与光学厚度的关系等问题。     

药物多晶型现象研究进展

药物多晶型自发现以来受到了广泛关注,多晶型的研究取得了巨大成就,但药物种类繁多,新药不断出现,多晶型的研究任务依然艰巨。通过对近10年来国内外药物多晶型研究相关文献的整理、分析与归纳,介绍了药物多晶型现象的研究意义、分析方法、多晶型转变的影响因素。     

稳定性研究在药品质量控制中的应用

药品的稳定性是关系到临床用药安全的重要信息。通常条件下,随着储存时间的延长,化学药品会出现降解,直接导致有效成分的减少和有害物质的增加,对临床用药安全带来风险。了解并掌握药品的稳定性信息,不仅关系到临床用药,也关系到药品的研制、生产、销售各个环节。本文以原料药的稳定性实验为基础,采用风险评估和统计分析工具,评估原料药的成分变化,为确定产品质量稳定性和有效期,进行产品注册和质量控制提供指导。     

Polymeric Gels and Their Application in the Treatment of Psoriasis Vulgaris: A Review

Psoriasis is a chronic skin disease, and it is especially characterized by the occurrence of red, itchy, and scaly eruptions on the skin. The quality of life of patients with psoriasis is decreased because this disease remains incurable, despite the rapid progress of therapeutic methods and the introduction of many innovative antipsoriatic drugs. Moreover, many patients with psoriasis are dissatisfied with their current treatment methods and the form with which the drug is applied. The patients complain about skin irritation, clothing stains, unpleasant smell, or excessive viscosity of the preparation. The causes of these issues should be linked with little effectiveness of the therapy caused by low permeation of the drug into the skin, as well as patients’ disobeying doctors’ recommendations, e.g., concerning regular application of the preparation. Both of these factors are closely related to the physicochemical form of the preparation and its rheological and mechanical properties. To improve the quality of patients’ lives, it is important to gain knowledge about the specific form of the drug and its effect on the safety and efficacy of a therapy as well as the patients’ comfort during application. Therefore, we present a literature review and a detailed analysis of the composition, rheological properties, and mechanical properties of polymeric gels as an alternative to viscous and greasy ointments. We discuss the following polymeric gels: hydrogels, oleogels, emulgels, and bigels. In our opinion, they have many characteristics (i.e., safety, effectiveness, desired durability, acceptance by patients), which can contribute to the development of an effective and, at the same time comfortable, method of local treatment of psoriasis for patients.     

有机颜料中禁限用危害化学品的产生和防止

在所有着色剂中有机颜料是一类具有高安全性的化学物质,但由于所用原料、专用助剂、添加剂以及现有制造技术和生产管理等原因,在有机颜料制造过程中仍会产生不少禁限用危害化学品。文中阐述了有机颜料中禁限用危害化学品的产生和防止,它们对推进我国有机颜料行业创新驱动和转型发展具有重要的意义。     

布洛芬固体脂质微颗粒的制备及其晶体构型研究

An emulsion-congealing technique is used to prepare solid lipid microparticles （SLM） containing ibuprofen with glyceryl behenate, tripalmitin and beewax as excipients. The difference of the solubility parameters between the excipients and ibuprofen are used to analyze their compatibility. Both the solubility parameter analysis and the experimental results show that glyceryl behenate is the best among the three excipients. The solid particles disperse well in aqueous phase when the drug loading reaches 10% （relative to lipid only）. Glycerides exhibit marked polymorphism and their rapid rates of crystallization accelerate the formation of metastable crystal modification. The metastable crystal modification characterizes high drug loading capacity but less stability. Increasing the content of lipophilic drug in a lipid matrix facilitates the transformation of excipients to more stable polymorphic forms.     

静注人免疫球蛋白(pH4)质量风险的生产控制

本文研究了静注人免疫球蛋白(pH4)使用可能存在的不良反应的情况。结果显示,温度对静注人免疫球蛋白(pH4)的结构、活性、产品质量、用药疗效等有明显的影响。在此基础上,提出了产品生产各工艺阶段的温度控制要求。同时,结合GMP管理的有关要求提出了产品生产过程中的药品质量风险管理的注意事项,结合药品的使用提出了生产过程中需要落实的质量风险控制措施,以此来确保产品的质量可靠、疗效确切、使用安全。在保证产品质量的同时,有效的控制药品使用过程中可能的风险,切实有效的保护患者权益,不将患者(身体虚弱,本身就是一种风险)置于药品质量、药品使用的潜在风险之中,更好的发挥药品的疾病治疗与预防作用。     

Application of generic principles of process intensification to solution crystallization enabled by a task-based design approach

The design of current industrial crystallizers is strongly focussed on optimization of known types of crystallization equipment. These crystallizers harbour various physical phenomena, which are strongly entangled. The application of generic principles of process intensification (PI) to crystallization processes requires individual control over physical phenomena. A new design method is applied that exploits elementary processing functions as building blocks for design instead of existing equipment, which enables the application of generic principles of PI. Innovations in the field of crystallization to manipulate shear forces, manipulate nucleation rates with external fields, and improve control over solvent removal with membranes are key technologies. A case study demonstrates the application of task-based design for solution crystallization. The results show how task-based design leads to high modularization of the process representation and model architecture. In addition, task-based design enables the application of generic PI principles, which results in a large flexibility to manipulate final product quality. Future needs include generalization of task-based design for crystallization and development of novel technologies for single task manipulation.     

Effect of polymorphism of isotactic polybutene‐1 on peel behavior of polyethylene/polybutene‐1 peel systems

The effect of polymorphism of isotactic polybutene‐1 (iPB‐1) on the peel behavior of the specific peel system low‐density polyethylene/polybutene‐1 (LDPE/iPB‐1) was investigated using wide‐angle X‐ray scattering, calorimetry, and the T‐peel test. Melt‐crystallization of iPB‐1, initially, yields tetragonal form II crystals which transform as a function of time to trigonal form I crystals. The kinetics of transformation at ambient temperature follows an exponential function, and is completed after about 50–75 h. The presence of LDPE in the peel system does not affect the transformation kinetics. The structure of the crystalline phase of iPB‐1 controls the peel force which decreases by about 25% during the crystal–crystal transformation in a blend with 20m% iPB‐1. The reduction of the peel force depends linearly on the mass fraction of iPB‐1 crystals in the peel system which further evidences the correlation between the crystal–crystal transformation of iPB‐1 and the peel‐characteristics of LDPE/iPB‐1 blends. Isothermal reorganization of crystals of LDPE is excluded as reason for the change of the peel‐performance of LDPE/iPB‐1 blends, since it is 5 to 10 times faster than the decrease of the peel force, and crystal–crystal transformation of iPB‐1, respectively. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

How to circumvent untoward drug crystallization during emulsion‐templated microencapsulation process

Unwanted drug crystals often form on the surface of PLGA microspheres or in an aqueous phase when a hydrophobic drug undergoes emulsion‐templated microencapsulation processes. In our study, over 70% of progesterone crystallizes in the aqueous phase when microencapsulation proceeds with a typical oil‐in‐water solvent evaporation process. During filtration employed for microsphere recovery, unentrapped drug crystals are collected alongside with progesterone‐containing microspheres. This phenomenon accompanies unfavorable consequences on the microsphere quality. In contrast, when microspheres are prepared with a new solvent extraction‐evaporation hybrid process, it is possible to completely avoid drug crystallization. Consequently, the new microencapsulation technique yields high drug encapsulation efficiencies of ≥ 90.8%, and the resultant microspheres show a homogeneous size distribution pattern. Also, the microsphere surface is free of drug crystals. For loading hydrophobic drugs into PLGA microspheres, the new microencapsulation process reported in this study has distinct advantages over commonly used emulsion‐templated solvent evaporation processes. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43768.     

Applications of the crystallization process in the pharmaceutical industry

The applications of the crystallization technique in the pharmaceutical industry as a purification and separation process for the isolation and synthesis of pure active pharmaceutical ingredients (API), co-crystals, controlled release pulmonary drug delivery, and separation of chiral isomers are briefly discussed using a few case studies. The effect of process variables and solvent on the polymorphism and morphology of stavudine is discussed. The implementation of external control in the form of feedback and real-time optimal control using cooling and antisolvent crystallization of paracetamol in water-isopropyl alcohol is introduced. Two methods to prepare micronsized drug particles, namely, micro-crystallization and polymer-coated API-loaded magnetic nanoparticles for pulmonary drug delivery, are discussed. The significance of co-crystals in drug administration is highlighted using the theophylline-nicotinamide co-crystal system. Resolution of chloromandelic acid derivatives, a racemic compound, is achieved using direct crystallization and diastereomeric salts crystallization. The crystal structures of diastereomeric salts of chloromandelic acid and phenylethylamine are determined. The structure comparison between the less soluble and more soluble salts shows that weak interactions such as CH/π interactions and van der Waals forces contribute to chiral recognition when the hydrogen bonding patterns are similar.