Solid Form

Polymorphism describes the fact that some materials with the same composition can exist in more than one crystalline form, characterized by different molecular packing. The ability to identify, understand, and control the polymorphic form of a material is important to multiple technical fields but is of special relevance to the field of pharmaceuticals.

大多数药品都用作固体（例如片剂，胶囊和吸入材料）和活性药物成分（API）的多态性形式具有直接感兴趣，因为它可以影响产品中产物的溶解行为，因此会影响生物利用率的溶解行为bob综合游戏。

In turn, the polymorphic form of the API can be affected by processing, formulation and storage conditions so it is often important to carry out checks during API synthesis route development, formulation development, storage and manufacture etc.

API可能以多种不同的多态形式存在，并且形式或形式组合的确定在特定样本中可能具有挑战性，尤其是当还有其他重要因素影响整体情况时，例如存在溶剂，水合物和无定形材料。因此，分析挑战可能很困难，并且通常在整个行业中使用多种方法。

The four leading techniques (X-ray Diffraction,NMR spectroscopy,拉曼光谱法和MIR spectroscopy）可从布鲁克获得。这些技术是高度互补的，并且都具有良好的信息，富含信息，无损性的信息，并且每个测定只需少量样品（10至100毫克）。

X-ray diffraction techniques play a crucial role for characterization of polymorphism at all stages within the drug life cycle. X-ray powder diffraction (XRD）广泛用于检测和识别（“手指打印”），用于已知和新的未知阶段。一旦确定，就可以进行晶体和无定形材料的定量相分析。bob综合游戏两者都是单晶X射线衍射（sc-xrdc)和XRD允许从头开始的决心rystal structures. SC-XRD is the most definitive and preferred technique; most significantly it enables the determination of absolute structures thus making it the tool of choice to characterize enantiomers. XRD plays a crucial role in structure determination using powders whenever suitable single crystals cannot be grown.

固态NMR光谱(SSNMR) is an excellent complementary analytical technique to characterize the solid forms of drug substance and drug product. SSNMR is used to identify different crystalline and/or amorphous forms, to monitor form conversion during API scale up, detect low amounts of other forms (e.g. crystalline in amorphous), measure relaxation times for prediction of physicochemical stability, and guard intellectual property. Similarly, drug product is uniquely suited to characterization by SSNMR because excipients typically do not significantly interfere with the analysis, even at low levels of drug substance in the drug product.

Time Domain NMR spectroscopy(TD-NMR) is ideal for the quantification of amorphous in the presence of crystalline form and/or excipients, with high accuracy, even when amorphous is present at low level. It is a non-invasive technique: samples remain intact after measurement. Samples can also be measured in their own container. TD-NMR has the additional advantages typically associated to benchtop instrumentation: ease-of-use, low cost and small footprint.

拉曼光谱法enables the fast and reliable differentiation between polymorphs and is therefore widely used to characterize materials in solid form. Products such as tablets can be analyzed by拉曼显微镜和成像，允许确定特定多晶型物的空间分布以及污染物的鉴定。当暴露于高温或压力时，该技术还可以用于研究不同多态性形式之间的转化。此外，手持仪器和高通量（HTS）选项为常规质量控制提供了强大的解决方案。

MIR spectroscopyis the routine method to identify chemicals, whereas in Far Infrared (FIR) spectral range back bone vibrations in crystal lattices are detected for polymorph differentiation. Bruker’s智能FTIR光谱仪with the uniqueFM技术提供一个步骤对完整的FIR-MIR光谱范围进行测量，并允许同时识别样品和多晶筛筛选。结合现代钻石减毒的总反射ATR配件，可以直接分析该物质，而无需进行任何样品准备，从而简化了药品研发和制造业中的日常工作。