Thermo Electron has revamped its Array Automation software for Raman spectrometers, in a move which it says enables pharmaceutical companies to reduce the polymorph and crystal analysis workload in drug discovery laboratories.
Chris Petty, director for vibrational spectroscopy products at Thermo Electron, explains: "It has been a trend in the last few years for pharmaceutical companies to do exhaustive polymorph analysis and crystallisation studies on candidate drug compounds much earlier in the drug discovery and development process. The net result has been a marked increase in the workload for the analytical groups in R&D."
One of the reasons for this is that the ability of salts to exist in different crystalline forms (polymorphisms) has been behind a number of high-profile patent challenges in the drug industry, perhaps most notably that relating to the histamine H2 antagonist Zantac (ranitidine) originated by Glaxo (now GlaxoSmithKline). In this case, generics companies were able to overturn the originator's exclusivity by developing forms of the drug that got around Glaxo's patent estates.
But aside from using crystal analysis as a defensive strategy, pharmaceutical companies are increasingly looking at how refinement of the crystal form of a drug can have a positive effect on its characteristics. For example, Johnson & Johnson has developed a new form of its epilepsy drug topiramate that is more soluble in water, opening up the potential form improved formulations such as fast-melt tablets.
Raman spectroscopy is often described as an ideal technique for the analysis of drug compounds, according to Thermo, because it is particularly sensitive to the subtle differences found between polymorphs and other crystal forms. It also requires no disruption to the crystalline form of a material for its analysis.
Recent developments in Thermo's Raman instrumentation, such as automated well-plate, capillary tube array handling, and the MicroStage FT-Raman microscope, have enabled new high-throughput screening applications, according to the company.
Combining Raman's ability to determine crystalline structures with automated sample handling capabilities, the Array Automation software enables high throughput screening applications on Thermo's Nicolet Almega XR dispersive Raman and NXR FT-Raman spectrometer lines.
The Nicolet Almega XR dispersive Raman microscope permits analysis of small amounts of individual crystals, while the FT-Raman spectrometer, using Thermo's exclusive MicroStage FT-Raman microscope, eliminates fluorescence interference.
The software automates the collection of spectra from either of these formats, and performs group or cluster analysis on the collected spectra.
"Prior to the Array Automation software, spectrum-to-spectrum comparison had to be done manually. Now, work that used to take a chemist half a day can be completed in five minutes," said Petty.