Counterfeit pharmaceutical products are a threat to global public health, patients, and the pharmaceutical industry. Consumers might be using a drug without the proper dosage or even without the proper ingredients, resulting in deterioration of their illness and potentially disability and death. Public health is threatened by the development of resistant strains of infectious agents. The industry is threatened by damage to its reputation resulting from the devastation caused by counterfeit versions of medicines, as well as the reduced sales when counterfeits replace legitimate product in the supply chain. Generally, counterfeit products are described as those containing the correct ingredients, but having been manipulated in an uncontrolled manner (for example, fake packaging), those containing the wrong active ingredients, and finally, those not containing any active ingredient at all. In all cases, the risk for the patient is important; although a product made with the correct ingredients might appear less harmful that one made with the wrong ingredients, its potency could be altered if the product has passed its expiration date, for example, or the dose level might be incorrect in a counterfeit product.

Currently, the most timely and practical way of identifying counterfeit medicines in the marketplace is the routine checking of packaging and use of covert markers and security features such as holograms. As soon as suspect counterfeit medicines have been sighted in the marketplace, they are further analyzed in the laboratory to confirm that they are counterfeit and to assess the potential harm that they might cause to patients.

Traditional methods of analysis for suspect counterfeit drug products include chromatographic assays for purity, potency, and content uniformity, and the laborious dissolution testing (which basically represent the QA/QC testing normally carried out on genuine drug products). A review of the analysis of counterfeit medicines by Olsen and colleagues (1) and Deisingh (2) showed a variety of analytical techniques being employed. There has been quite some interest in using near-infrared (NIR) spectroscopy (3–6). Recent work published by the USFDA (7) pointed to the additional information contained in NIR chemical images of tablets purchased on the Internet, and the potential value of this additional knowledge in qualifying both the potency and the quality of the formulation as a whole. The latter is generating increasing interest as a novel approach providing improved control of manufacturing of pharmaceutical products through a better understanding of the products themselves as a part of the Process Analytical Technology initiative (8) put forward a few years back by the USFDA.

In this work, we describe the use of NIR-chemical imaging (NIR-CI) using a focal plane array detector for the identification and characterization of counterfeit drug products. The analysis is performed solely using tablets of genuine origin as neither controls nor calibration procedures requiring prepared samples are necessary.

Materials and Methods

Drug Products

A total of 30 tablets of an antimalarial drug, all white, cylindrical, scored on one side, and embossed with the trade name on the other side, were investigated. Of these, 10 tablets were recognized as genuine tablets, obviously containing the right active pharmaceutical ingredient (API) (G); seven counterfeit tablets contained paracetamol (acetaminophen) as substitute API (P); and 13 counterfeit tablets contained another substitute API (A). The tablets were analyzed whole, without any sample preparation.

Some genuine tablets and tablets containing paracetamol as substitute API were imaged in the blister pack.

Instrumentation

A Spectral Dimensions NIR-CI2450 spectrometer (Malvern Instruments, Olney, Maryland) equipped with an InSb focal plane array detector (320 × 256 pixels) was used for this work. Image cubes of each tablet were acquired in the spectral range 1400–2400 nm at 10-nm steps and the field of view was set to 12.8 mm × 10.2 mm; this field of view encompasses approximately 80% of the area of the tablet and provides a pixel magnification of 40 μm. A set of tablets of unknown identity were positioned on a single sample slide and an image cube of the whole set was acquired at a magnification of 125 μm/pixel. All data were acquired in diffuse reflectance, a process by which the source radiation interacts with the surface of the sample, and the radiation diffusely reflected in the direction of the camera is measured. This sampling method is optimal for pharmaceutical products because samples can be analyzed intact and therefore are still available for testing with other methods. Dark and bright background image cubes were acquired at initiation followed by successive sample cubes. One image cube was acquired from each sample. Each image cube contained 81,920 full NIR spectra and required a collection time of approximately 3 min.