2GlaxoSmithKline, New Frontiers Science Park (North), Harlow, CM19 5AW, UK

The development of novel pharmaceuticals is driven by the requirement for high efficacy while retaining reduced side effects. This means that new medicines are very often relatively low dose (below 10% w/w drug substance in a tablet) and therefore they pose significant analytical challenges. Typical requirements include chemical identification of the drug substance, its crystalline form, the presence of any degradants and the distribution of drug substance and excipients.

Raman spectroscopy is becoming one of the favoured techniques for looking at tablets. Raman is a non-invasive and non-destructive technique that is very important in the pharmaceutical industry. In addition, with a Raman microscope, it is possible to obtain spectra from particles of micrometer dimensions. This means that limits of detection can be lower than those from conventional Raman techniques

The most common Raman experiment for analysing tablets is the point-by-point mapping approach. This can be very time consuming and therefore difficult for trouble shooting or on-line analysis. One way of increasing the speed of analysis would be to increase the laser power used (and thereby decrease the acquisition time). This approach, however, increases the probability of causing chemical degradation. Using a diffractive optic avoids this problem by splitting the incoming laser beam into several spots. In the present experiment, we have used a diffractive optic to split the laser beam into three spots that are 100m m apart. To retain the confocality of the Renishaw RM1000 Raman microscope, the diffractive optic has been placed into the beam path just before the fixed mirror/edge filter. For recording of the collected light, and subsequent analysis, we have used the line mapping software on the Renishaw instrument to define three active areas on the CCD, each corresponding to one of the focal spots.

The diffractive optic allows the recording of several spectra simultaneously and hence decreases the amount of time required to sample the tablet. This approach is similar to the line mapping technique. Advantages of the diffractive optic multi-point technique over the line mapping approach are that the full confocality and spatial resolution of the Raman microscope are maintained.