Pearlescent coatings. According to Colorcon's Oza, the pearlescent pigments in fully-formulated film coatings are also considered PCIDs under the 2009 FDA draft guidance. Pearlescent coatings, in general, could increase counterfeiting protection because the unique color-shifts across the tablet surface are difficult to duplicate without knowing the specific combination of pigment properties and processing procedures.

Explains Oza, "A multitude of colors can be achieved using the same chemical entity controlled by various parameters that are difficult to reverse-engineer. Pearlescent coatings are also easily recognized by physicians, pharmacists, and patients as the original manufacturer's product. In this sense, visual identification can be further enhanced by using unique colors, coupled with a tablet's shape and size, or by using printing methods to place unique images and logos on the tablet's surface."

In terms of regulatory implications, Oza says that the pigments contained in the pearlescent coatings meet current 21 CFR colorant regulations. The coatings are custom-developed from approved GRAS ingredients or listed in FDA's IID; produced under cGMP conditions; compatible with existing coating processes; and typically have no impact on dissolution or stability.

Figure 1 (ARmark): Microtags, with unique information specified by the brand owner, can be embedded in a space on a tablet smaller than the diameter of a human hair. Magnified image shows microtags on the surface of a blue film-coated tablet.

Supply chain. Covert on-dose microtag technology is also important for addressing growing supply-chain concerns throughout industry because it enables companies to use the information embedded within the microtag to immediately understand a product's traceability. "Not only can the microtags prove authenticity of the solid oral-dosage form, but they can also contain information that sheds light on the distribution practices once a product leaves the manufacturing site," explains ARmark's D'Ottavio.

"From a track-and-trace perspective, the microtags can provide the technology to distinguish authentic product from adulterated supplies," he says. "But when these tags include information, such as batch or country codes, the drug manufacturer can take a closer look at understanding where the product originated to gain insight as to how the product was handled in the field."

Looking ahead, Colorcon's Oza comments on what the future of drug-anticounterfeiting technology may hold. "Due to the complexity of today's distribution system, no single anticounterfeiting technology can guarantee full counterfeit protection. However, if a drug product is designed with layers of identification on the dosage itself, and then packaged with a variety of features that are hard to duplicate, counterfeiters may turn their sights elsewhere," he says. "The key is to ensure that a pharmaceutical is made difficult to duplicate. Procuring noncommodity coating options will impart the most security."

Accelerating tablet shape selection: Pfizer and DEM Solutions' predictive computational model

The following section is provided by William R. Ketterhagen, senior scientist, and Mary T. am Ende, associate research fellow, both with Pfizer Worldwide Research & Development, and by Richard D. LaRoche, vice-president of engineering and US general manager, and Oleh Baran, senior consulting engineer, both with DEM Solutions. The authors discuss a recently developed predictive computational model that can help guide pharmaceutical manufacturers in the selection of tablet shape and operating parameters for a given equipment geometry to ensure film-coating uniformity.

Designing and developing robust drug products can be a costly endeavor, especially when commercial-scale studies must be performed to determine nonscalable or unpredictable process parameters. Even in tablet-film coating, where some aspects, such as the thermodynamic conditions in the pan and spray atomization are relatively well understood, coating uniformity can vary for tablets of different core shapes and different coating-process conditions (1, 2). In this regard, the coating process is not entirely scalable from laboratory studies due to differences in tablet-mixing in the pan (3). The introduction of a new tablet shape, for example, can result in unexpected variations in the uniformity of film-coating thickness, requiring physical testing that is costly in time, materials, and labor.

Although some experimental work can be avoided through the use of models, poor coating uniformity often requires experimental trials to determine the operating conditions that produce desired coating results when moving from laboratory to commercial scale (1, 2). As a solution, Pfizer Reseach and Development has developed a predictive computational model using EDEM, discrete element method (DEM) software developed by DEM Solutions. The method has been confirmed experimentally to guide selection of the tablet shape and operating parameters for a given equipment geometry such that uniform film-coating thickness is obtained (4).