Until recently, Raman spectroscopy was not widely applied in the pharmaceutical industry. However, in the last few years, developments within the pharmaceutical industry, coupled with improvements in Raman instrumentation, have generated renewed interest in the technique. It is already proving to be a valuable tool in the analysis of pharmaceutical polymorphs and now looks destined to find increasing application throughout the pharmaceutical industry.

After 80 years of maturing in academic laboratories around the world, Raman spectroscopy has finally begun to make a significant impact in the industrial environment, finding particular application in the semiconductor, chemical and synthetic polymer industries. While still not as widely employed in the pharmaceutical industry as its cousins, near- and mid-infrared (IR) absorption spectroscopies, it has recently found a particular niche in the analysis of pharmaceutical polymorphs. Raman spectra have proved highly characteristic of different polymorphic forms of pharmaceutical compounds and the ability to obtain spectra without the need for potentially polymorph changing sample preparation has proved ideal for applications from polymorph screening to patent litigation. This high profile application of Raman spectroscopy has lead to greater acceptance of, and interest in, the technique within the pharmaceutical industry. With the advent of the US Food Drug Administration's (FDA) process analytical technology (PAT) initiative, Raman spectroscopy is increasingly being considered for applications in the pharmaceutical manufacturing environment.

So that a reader unfamiliar with Raman spectroscopy can begin to determine its suitability to their own particular application, the basic principles and features of the technique are outlined with particular reference to practical application in a pharmaceutical environment. Comparisons are made with IR spectroscopy with which the reader may be more familiar. Some example applications are presented including the detection and identification of pharmaceutical polymorphs. The potential of the technique as a PAT tool will be discussed separately in Part II.

Figure 1 Schematic overview of the basic experimental arrangement to perform Raman spectroscopy.

While IR spectroscopy is essentially based on illuminating the sample with a broad range of wavelengths of IR light and measuring which are absorbed, a Raman spectrum is obtained by illuminating the sample with a single wavelength of light from a laser and collecting and analysing the resulting scattered light (Figure 1). Briefly, the basic experimental arrangement to perform Raman spectroscopy includes the following steps:

• To obtain a Raman spectrum the sample is illuminated with light from a laser.
• The molecules in the sample 'scatter' the incident laser light. Some of this scattered light contains detailed information about the molecular properties of the sample.
• The scattered light is collected and analysed using a Raman spectrometer to produce a Raman spectrum.
• Raman spectra are generally clear, well resolved and rich in features facilitating detailed and unambiguous interpretation.
• The spectra contain large amounts of information about chemical composition, intra- and intermolecular phenomena, and the longer range structure of a sample.