药物共晶多晶型的研究进展

药物多晶型现象是影响药物稳定性和疗效的重要因素。近年来,越来越多的共晶体系被发现存在多晶型现象,而且不同晶型的共晶也表现出了性能上的差异。共晶多晶型的研究也因此受到了越来越多的关注。综述了近几年有关药物共晶多晶型的报道,解释了共晶多晶型的概念,并对其进行了分类（合成子多晶型、堆积多晶型、构象多晶型以及互变异构多晶型）,重点介绍了目前共晶多晶型的筛选方法。此外,强调了共晶药物由于晶型不同而引起的性能差异。     

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。     

红外光谱技术在药物多晶型分析中的应用

概述了药物多晶型的概念和基本特点,通过红外光谱分析技术具有速度快、不破坏样品、不需试剂和在线测定的优势等特点,对近年来国内外采用红外光谱技术在药物多晶型鉴定方面的应用文献进行研究,整理、分析与总结,详细介绍了漫反射傅里叶变换红外光谱法、近红外光谱法和显微红外法在药物多晶型的应用和未来的发展方向。     

固体药物的多晶型现象及研究进展

固体药物中的多晶型现象普遍存在,且多晶型影响着固体药物的质量和疗效,故对固体药物多晶型现象进行研究具有十分重要的意义。从药物晶型及多晶型现象、优势药物晶型、固体药物的转晶现象、晶型影响药品质量的评价方法、药物多晶型的研究现状及进展等五个方面介绍了固体药物的多晶型现象及研究进展,为固体药物多晶型现象研究提供参考。     

近红外光谱法在药物多晶型定量中的研究策略

为建立可靠、准确的药物多晶型定量研究方法，根据国内外晶型研究指导原则和NIRS分析技术重要标准及实际研发工作经验，从代表性样本集的制备、NIRS建模、方法验证等方面，对多晶型定量研究的关键问题进行系统的分析与探讨研究，解决近红外光谱(Near Infrared Spectroscopy, NIRS)分析技术在多晶型定量研究中的应用问题，对后续制药企业应用NIRS法进行产品质量控制提供参考，通过综述NIRS在药物多晶型定量研究中方法开发和验证的基本策略，提供科学的NIRS多晶型定量研究思路。     

熔体结晶应用于药物多晶型研究进展

综述了熔体结晶应用于药物多晶型领域的研究进展，包括常规熔体结晶、聚合物诱导熔体结晶、纳米限域熔体结晶和熔体微液滴培养单晶技术，以期助力药物多晶型和固态化学研究。     

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。     

农药多晶型研究进展

农药的不同晶型会使产品的物理化学性质有所差异，进而影响作用效果，因此农药多晶型一直是研究的重点。介绍了农药多晶型，以及多晶型的制备和表征方法。此外，重点介绍了发现的不同类别的农药多晶型。通过综述农药多晶型的研究现状，对促进农药多晶型的研究具有重要的意义。     

药物晶型转化与控制的研究进展

药物晶型可显著影响药品质量、安全性和有效性,国家"医药工业十二五发展规划"将药物晶型研究列为提升药物质量安全的主要任务和重点技术。本文介绍了药物多晶型的溶解度行为以及晶型转化的液相和固相介导机理,溶剂、添加剂/模板剂对药物晶型的控制有着重要的作用,而物理场效应(超声波、微波、超重力场等)对晶型转化过程起强化效应;过程分析技术的快速发展为晶型转化机理的研究以及过程优化、控制提供了先进手段。未来药物晶型转化与控制的研究将聚焦分子的组装与调控行为、过程分析以及药物的构效关系等方面。     

有机晶体多晶型调控研究进展

近些年涌现出许多新型的多晶型调控方法,其中利用添加剂和界面组装对有机晶体多晶型进行调控已成为研究热点。分子模拟可以在分子水平上研究晶体结构形貌及异相成核中的界面作用机理,因此被广泛应用于揭示晶体成核和生长过程中的关键问题。文中综述了近些年来国内外利用添加剂和界面组装技术调控有机晶体多晶型的实验研究进展,以及利用分子模拟方法预测晶体形貌进而探索界面分子作用调控多晶型机理的研究进展。最后,对多晶型实验和模拟方面的研究手段进行了总结和展望。     

超临界流体构筑微粒技术作为药物制剂研发平台的应用

在药物递送系统的研发和应用过程中,制备结构可控的微粒药物制剂是重要且有效的方式。本论文阐述了超临界流体构筑微粒技术在药物递送系统创新的应用,包括纳微米级药物微粒、药物多晶型控制和复合粒子制剂。总结了不同类型的超临界流体工艺特点及其粒子微观结构调控的机理。基于热力学和流体动力学两因素,利用超临界流体构筑微粒技术调控构筑药物活性成分的微观结构,包括粒度、晶型、晶习和粒度分布。     

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.     

硫酸氢盐氯吡格雷药物晶型测定

利用傅立叶红外光谱(FTIR)、差示扫描量热分析(DSC)、热重分析(TGA)、X-射线衍射(XRD)对硫酸氯吡格雷的晶型进行了测定与分析,结果表明,XRD在晶型测定与分析中优势明显,并通过全谱拟合获得晶型的晶胞参数.     

Development of a ligation-based impedimetric DNA sensor for single-nucleotide polymorphism associated with metabolic syndrome

Single-nucleotide polymorphism (SNP) detection is becoming important in molecular diagnostics, clinical assay, and novel drug development. Electrochemical methods are well suited for the DNA diagnostics system. Since electrochemical reactions directly emit an electronic signal, expensive signal transduction equipment is not required. We describe the development of a novel DNA sensor that utilizes impedance spectroscopy and DNA ligation reaction on a gold electrode. Impedance spectroscopy enables label-free detection and is nondestructive and useful in equivalent circuit models for interpretation on an electrode surface, whereas from the ligation reaction, the specificity is derived by the allele-specific oligonucleotide of the capture probe on immobilized gold electrode. In other words, DNA diagnostics system using the combination of impedance spectroscopy and ligation reaction is simple, rapid, and allele specific. In this report, we have described a ligation-based impedimetric DNA sensor and the analysis of Trp64Arg polymorphism in the beta3-adrenergic receptor gene (ADRβ3).     

GSTM1/T1 Genotypes and Benzo(A)Pyrene Hemoglobin Adducts in Maternal and Fetal Blood

Both genetic and environmental factors are involved in the development of cancer. The capacity to metabolize certain drugs and carcinogens is known to be variable in humans and appears to be of critical importance in determining the risk an individual has of developing cancer when exposed to carcinogens. For many phase I and phase II enzyme systems involved in foreign compound metabolism it is now understood that germ-line genetic variation within the genes encoding these enzymes leads to altered phenotypic expression impacting the metabolic capacity of the individual. This genetic variation is referred to as genetic polymorphism and the study of the association between genetic polymorphism and the resulting phenotypic changes in drug or foreign compound metaboism is referred to as pharmacogenetics. This variation in metabolic capacity is linked to environment–gene interactions on carcinogenesis and has been well demonstrated by enzymes that are involved in the metabolism of carcinogens including several human cytochrome P450 enzymes as well as certain glutathione S-transferases and N-acetyltransferases. The genetic lesion may involve a single but critical base pair change or complete gene deletion. Screening assays based on PCR amplification coupled to restriction fragment length polymorphism (RFLP) analysis or allele specific PCR have been developed to correlate genetic polymorphism with phenotypic expression and susceptibility to genotoxicity or carcinogenesis. The phase II enzymes, including GSTs, N-acetyltransferases, as well as epoxide hydrolase, are all involved in the detoxification of activated metabolites of carcinogens, including those carcinogens found in tobacco smoke. The substrates of GSTs include benzo(a)pyrene as well as other carcinogens. In the present study, we investigated the relationship between polymorphism of glutathione S-transferase in maternal and fetal cord blood samples obtained at delivery and correlated genotype with presence of hemoglobin adducts to the tobacco carcinogen benzo(a)pyrene.     

青年教师提高体内药物分析教学能力的思考

体内药物分析在新药研制、临床合理用药等方面具有重要意义,青年教师在体内药物分析教学中应加强相关基础知识的联系与贯通,强化体内药物分析课程设计的训练,合理处理科研与教学间转化和联系,不断的提高体内药物分析的教学能力,从而提高教学质量,培养药学应用型人才。     

Formulation and in vitro evaluation of transdermal delivery of zidovudine—An anti‐HIV drug

This study was designed to develop matrix type of transdermal‐controlled delivery system for zidovudine using Eudragit L100 by varying the amounts of drug in addition to polyethylene glycol as a plasticizer and Tween 80® as a penetration enhancer. Transparent smooth and flexible films were characterized for weight, thickness uniformity, and drug content. Drug interactions with the polymer films were studied by differential scanning calorimetry, whereas X‐ray diffraction was used to understand the drug polymorphism in the films. The in vitro drug release experiments were performed in phosphate buffer using the Keshary‐Chien diffusion cell. Variations of drug release profiles were analyzed using the Ritger and Peppas empirical equation to describe the type of release mechanism. The exponent n values of the equation varied over the wide range of 0.75–2.23, suggesting non‐Fickian to super Case‐II type of diffusion transport. Statistical analyses of release data performed by the analysis of variance (ANOVA) method indicated significant differences within experimental measurements. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011