www.spectroscopyonline.com 26 Spectroscopy 19(4) April 2004 Dear and gentle readers, this month I present an important tool in the process analytical technologies (PAT) initiative: Near-infrared chemical imaging (NIR-CI). You might wonder why I am seemingly concentrating on IR and NIR. The an- swer is quite simple: I need all the heat I can get, here in New York. Seriously, E. Neil Lewis, Joe Schoppelrei, and Eunah Lee of Spectral Dimensions (Olney, MD) have put to- gether an excellent explanation of what NIR-CI is and what its part in PAT is and will be. For those of you who do not know Neil Lewis, he is one of the pioneers in IR and NIR im- aging. He has won numerous awards for his research at the National Institutes of Health (NIH) and subsequent accom- plishments. It is truly exciting to have this paper in my hum- ble column and I know you will find it informative and enter- taining. he US Food and Drug Administration (FDA) recently released a new guideline strongly advocating the use and development of new measurement technologies in pharmaceutical manufacturing (1). The process analytical technology (PAT) initiative, as it is known, promotes the use of techniques that enable the monitoring of critical process parameters during pharmaceutical manufacturing. The goal is to not only enable process measurement but, more impor- tantly, to enable process understanding and ultimately process optimization. Although FDA historically has focused on pu- rity and potency as its yardstick of product quality, in the fu- ture more time will be spent trying to address issues dealing with physical processes. For example, what effects, if any, do small changes in the blending, drying, pressing, coating, or other manufacturing steps have on the final dosage form? To encourage the PAT initiative FDA is streamlining the mecha- nism for adopting new technologies in pharmaceutical manu- facturing. The Role of Near-infrared Chemical Imaging (NIR-CI) A typical tablet is not just a pressed block of a single material, but rather a complex matrix containing one or more active pharmaceutical ingredients (APIs), fillers, binders, disinte- grants, lubricants, and other materials. A basic problem in pharmaceutical manufacturing is that a relatively simple for- mulation with identical ingredients can produce widely vary- ing therapeutic performance depending upon how the ingre- dients are distributed in the final matrix. More potent APIs can be formulated at dosages of 5 mg or less, but the finished tablet still must be large enough for convenient handling. In this case, maintaining content uniformity is even more cru- cial. Pharmaceutical makers also are developing advanced tablets for drug dosage management, which can provide longer, flatter, or sometimes complex bloodstream profiles. Approaches include the use of barrier layers, cored tablets, se- lective-release microspheres, and even osmotic pumps. These tablets essentially are highly engineered drug delivery systems in which the physical structure is as critical as the chemical composition. Existing analytical techniques such as high performance liquid chromatography (HPLC) and mass spectrometry (MS) often are used to accurately determine the gross composition of a dosage form, but they provide no information about the distribution of the individual components. The manner and duration of component release is examined through dissolu- tion testing. However, this provides no insight into the cause of the profiles obtained. All of these techniques require de- struction of the sample, making it difficult or impossible to trace the sources of failures or anomalies. Spectroscopic techniques enable rapid, nondestructive analysis of samples and can be employed at a number of points in the pharmaceutical development and manufactur- ing process. In particular, NIR spectroscopy quickly is becom- ing a workhorse technique for the industry due to its high in- Molecular Spectroscopy Workbench Near-infrared Chemical Imaging and the PAT Initiative NIR-CI adds a completely new dimension to conventional NIR spectroscopy. E. Neil Lewis, Joe Schoppelrei, and Eunah Lee T Emil W. Ciurczak works as a consultant with Integrated Technical Solutions, 77 Park Road, Goldens Bridge, NY 10526. He can be reached via e- mail at: emil@ciurczak.com.