药品中结晶相检测方案(X射线衍射仪)

thermoscientific APPLICATION NOTE XRD Investigation of lbuprofen withARL EQUINOX 100 in Transmission Mode Introduction X-ray diffraction is a standard technique to investigatepharmaceutical compounds and formulations， both inproduction and academic research. As the need for newdrugs to better serve society increases， so does the demandfor versatile X-Ray diffractometers to support pharmaceuticalresearch. Active pharmaceutical ingredients (APIs) and othercompounds must pass rigorous screening like saltformation， co-crystallization or polymorphism duringresearch and production quality control. These stepscan conveniently be achieved using powder X-raydiffraction thanks to the inherent sensitivity and ability todifferentiate between different crystallographic structures.It is also possible to perform dynamic studies， follow thecrystallization behavior of compounds in different solvents ornon-ambient conditions. It is now even possible to routinelysolve the crystal structure of new compounds from powderdata. In addition， X-ray diffraction affords the ability to traceimpurities during synthesis， thus improving processes. Instrument The Thermo ScientificARLEQUINOX Series representa portfolio of XRD instruments from simple，easy to usebench-top systems for routine analysis to more advancedfloor-standing， high performance， research grade systems. The Thermo Scientific" ARLM EQUINOX 100 employs acustom-designed 50 W Cu or 15 W Co high-brilliancemicro-focus tube with mirror optics which does not requirean external water chiller. The unit can be transportedbetween laboratories or into the field without requiring anyspecial infrastructure. The ARL EQUINOX 100 provides very fast data collectioncompared to other diffractometers due to its uniquecurved position sensitive detector (CPS) that measuresall diffraction peaks simultaneously and in real time. It istherefore well suited for transmission mode measurements(cf. Figure 1). Figure 1： ARL EQUINOX 100 diffraction system Experimental Ibuprofen samples from four different vendors were groundand loaded into transmission measurement cups usingscotch tape. Each sample was rotated and measuredfor 10 minutes using Cu-Ka radiation (1.541874 A). Dataprocessing and evaluation was performed using MATCH!equipped with the COD database for qualitative phaseanalysis. Figure 2： ARL EQUINOX 100 in transmission measurement mode Results Ibuprofen products (200 mg)， both brand-name and generic，usually contain a variety of non-API compounds which tend todiffer between vendors. Those include cellulose， pigment orfilming agents. XRD is the ideal technique to clearly distinguishbetween crystalline phases in such mixtures. Presented beloware four samples from different vendors showing differentformulations (peak positions are indicated as vertical lines).Therefore the diffraction patterns of the different productsexhibit differences which are clearly visible (cf. Figure 3). Figure 3： Diffraction pattern (4-50°20) from four vendors (patterns areshifted vertically for better comparison) There are many generic products on the market whereofone was investigated and the only crystalline phase isIbuprofen (cf. Figure 4). Figure 4： Diffraction pattern (4-50°20) of generic product These results are also comparable to one brand productwhere only traces of talc (green， used as a lubricant) aredetectable (cf. Figure 5). la ll 1111 Except from these two examples there are vendors whichuse additives (additionally to talc) to accomplish differentrequirements (cf. Figure 6). In contrast to Brand Product3， Brand Product 2 contains Sodium Citrate (purple) butno Calcite (grey) (arrows mark differences). Sodium Citrateand Calcium Carbonate are used as buffering agents tominimize the harm to the stomach caused by the Ibuprofen，whereas Sucrose (blue) yields a more pleasant taste. Figure 6： Diffraction pattern (4-50°20) Brand Products 2 and 3 Conclusion The good resolution of the ARL EQUINOX 100 in transmission mode geometry enables the ability to clearlyresolve the crystalline phases in different pharmaceuticalmixtures. A 10-minute measurement time is enough toperform a qualitative phase analysis and also detect tracephases. Hence the ARL EQUINOX 100 is an easy-to-use toolfor all realms of pharmaceutical research or production frompreformulation through to QA/QC of the final drug product. SCIENTIFIC Find out more at www.thermofisher.com/equinoxS CIENTIFI CFor Research Use Only. Not for use in diagnostic procedures. @ Thermo Fisher Scientific Inc. All rights reserved. All trademarks 在与制药相关的工业生产和学术研究中，XRD是分析其成分和配方的标准技术。因为不断需要新型药物来更好地满足社会需求，所以对X射线衍射仪的需求也在不断增长以支持相关的研究。在药物的研发和生产控制过程中，其活性成分（APIs）或者其他化合物都需要经过严格的筛选，例如盐、共结晶和多晶转变等。XRD具有较高的灵敏度和区分不同晶体结构的能力，可以轻松地完成这些应用。XRD也可以用于动态研究，跟踪化合物在不同溶剂和非环境条件下的结晶行为，甚至可以通过粉末衍射数据确定新化合物的晶体结构。此外，XRD还可以对合成过程中的杂质进行追踪，以改进合成工艺。