欧洲药典8.0 多晶型现象 中英文.doc

5.9. POLYMORPHISM5.9. 多晶型现象Polymorphism (or crystal polymorphism) is a phenomenon related to the solid state; it is the ability of a compound in the solid state to exist in different crystalline forms having the same chemical composition. Substances that exist in a non-crystalline solid state are said to be amorphous.多晶型现象（或晶体多态性）是一种与固态有关的现象；它是固态化合物以同一化学组成而不同结晶形式存在的能力。物质以非结晶性固体存在时称为无定形。When this phenomenon is observed for a chemical element (for example, sulfur), the term allotropy is used instead of Polymorphism.当这一现象出现在化学元素中时（如硫），用术语同素异形体代替多晶型现象。The term pseudopolymorphism is used to describe solvates (including hydrates), where a solvent is present in the crystal matrix in stoichiometric proportions; the term may also be extended to include compounds where the solvent is trapped in the matrix in variable proportions. 术语伪多晶常用于描述溶剂化物（包括水合物），其中的溶剂以一定化学计量比存在于晶体中；该术语也可以引伸到包含不同比例溶剂于晶体中的化合物。However the term pseudopolymorphism is ambiguous because of its use in different circumstances. It is therefore preferable to use only the terms “solvates” and “hydrates”.然而，伪多晶由于在不同的情形下使用容易引起混淆。因此，最好只使用“溶剂化物”和“水合物”来表达。Where a monograph indicates that a substance shows polymorphism, this may be true crystal polymorphism, occurrence of solvates, allotropy or occurrence of the amorphous form.当专论中指明一种物质显示多晶型现象，可能是真正的多晶型，存在溶剂化物，同素异形体或存在无定形形式。The identity of chemical composition implies that all crystalline and amorphous forms of a given species have the same chemical behaviour in solution or as a melt; in contrast, their physico-chemical and physical characteristics (solubility, hardness, compressibility, density, melting point, etc.), and therefore their reactivity and bioavailability may be different at the solid state.化学成分的一致性意味着给定品种的结晶体和无定型形式在溶液中具有相同的化学行为或熔融表现；表明在给定物种的所有结晶和无定形形式具有在溶液中或作为熔体相同的化学特性；与此相反，它们固态时的物化和物理特性（溶解性，硬度，压缩率，密度，熔点等）可能不同，因此固体状态下的反应性和生物利用度也可能不同。When a compound shows polymorphism, the form for which the free enthalpy is lowest at a given temperature and pressure is the most thermodynamically stable. 当一个化合物显示多晶型现象，那么在给定温度和压力下，自由焓最低的形态即热力学最稳定形态。The other forms are said to be in a metastable state. At normal temperature and pressure, a metastable form may remain unchanged or may change to a thermodynamically more stable form.其他形态则为亚稳态。在正常温度和压力下，亚稳态形式可能保持不变或变化为热力学更稳定的形式。If there are several crystalline forms, one form is thermodynamically more stable at a given temperature and pressure. A given crystalline form may constitute a phase that can reach equilibrium with other solid phases and with the liquid and gas phases.如果有多个结晶形式，在给定的温度和压力下只有一种形式热力学更稳定。那么这种给定晶形可以与其他固相、液相、气相形成平衡相。If each crystalline form is the more stable within a given temperature range, the change from one form to another is reversible and is said to be enantiotropic. 如果在给定温度范围内每个结晶形式都比较稳定，那么从一种形式到另一种形式的变化是可逆的，称为互变。The change from one phase to another is a univariate equilibrium, so that at a given pressure this state is characterised by a transition temperature. However, if only one of the forms is stable over the entire temperature range, the change is irreversible or monotropic.相转变是一个单变量平衡，在给定压力下，用相转变温度来特指这种状态。然而，如果在整个温度范围内只有一个的形式是稳定的，该变化是不可逆的或单向的。Different crystalline forms or solvates may be produced by varying the crystallisation conditions (temperature, pressure, solvent, concentration, rate of crystallisation, seeding of the crystallisation medium, presence and concentration of impurities, etc.).不同的结晶形式或溶剂化物可以通过改变结晶条件（温度，压力，溶剂，浓度，结晶速率，引晶技术，杂质存在和浓度等）来制造。The following techniques may be used to study polymorphism:以下技术可以用来研究多晶型现象： X-ray diffraction of powders (2.9.33), X射线粉末衍射（2.9.33） X-ray diffraction of single crystals,单晶X射线衍射 thermal analysis (2.2.34) (differential scanning calorimetry, thermogravimetry, thermomicroscopy),热分析（2.2.34）（差示扫描量热法，热重分析法，热显微镜法） microcalorimetry,微量热法 moisture absorption analysis,吸湿分析 optical and electronic microscopy,光学和电子显微镜 solid-state nuclear magnetic resonance,固相核磁共振 infrared absorption spectrophotometry (2.2.24),红外吸收光谱（2.2.24） Raman spectrometry (2.2.48),拉曼光谱（2.2.48） measurement of solubility and intrinsic dissolution rate,溶解度和固有溶出率的测量 density measurement.密度测定These techniques are often complementary and it is indispensable to use several of them. 这些技术通常是互补的，必须同时使用其中的几个。Pressure/temperature and energy/temperature diagrams based on analytical data are valuable tools for fully understanding the energetic relationship (enantiotropism, monotropism) and the thermodynamic stability of the individual modifications of a polymorphic compound.根据分析数据绘制的压力/温度图和能量/温度图有利于充分理解能量关系（互变现象，单变现象）和多晶型化合物单变量调整的热力学稳定性。For solvates, differential scanning calorimetry and thermogravimetry are preferable, combined with measurements of solubility, intrinsic dissolution rate and X-ray diffraction.对于溶剂化物，最好选择差示扫描量热法和热重分析法，同时结合溶解度、固有溶出速率和X-射线衍射的测定。For hydrates, water sorption/desorption isotherms are determined to demonstrate