The use of the medicinal tablet dates back to ancient Egypt, making it one of the earliest pharmaceutical dosage forms. These solid compounds of active substances and excipients are often covered in some form of superficial coating material.
The application of a polymeric film or sugar coat to a tablet can mask the taste or odor of the medication, delay the release of the drug, enhance bioavailability, and preserve the shape of the tablet. Enteric coatings can insulate the active components of the tablet from stomach acids and protect the stomach lining from potentially aggravating medications.
Active coatings may be applied to counteract potential interactions between multiple APIs. Understanding the finer points of coating processes and monitoring for innovations in the field are crucial to maximizing the potential of commercial tablet manufacturing.
Commercial tablet manufacturing employs a range of different coatings, but the fundamental coating processes remain the same.
Large batches are identified, and the recipe of either sugar or film coating is selected. The batch of tablets is loaded and dispensed under rigorous monitoring to ensure accurate dosing. There is a warming process, and then the coating is applied, usually in the form of a spray, and the tablets are rolled. The batch of tablets remains in the coating pan until they have dried and cooled. These basics steps and the instrumentation involved may be altered depending on the chemical composition of the tablets or the coatings. Other variables in the process can involve the spacing of nozzles, the size and formation of drops, and the general spray patterns.
Since the efficacy of pharmaceutical tablets is entirely reliant on the proper application of coatings, accurate yet flexible control systems are a crucial component of the commercial tablet manufacturing process. Management systems to track the parameters of individual coating recipes and loop control systems that utilize setpoint profile programming are fundamental. Given the complexity of the control strategies, sequential control is of paramount importance. The precise graphics of the operator display allows for the controlled collection and analysis of coating system data, among other parameters.
Even with all these control systems, however, accurately and consistently identifying the endpoint of the coating process is not always simple. Determining the thickness of the coating is especially difficult, as evaluating tablets for changes in weight or diameter yield inconsistent results, and visually inspecting cross-sections can be even less precise.
Not only are these methods prone to error, time-intensive, and approximate rather than precise, but they are nearly impossible to employ in-line. This presents a serious complication in commercial tablet manufacturing, as the thickness of a tablet’s coating controls the dissolution and performance of the drug.
Optical coherence tomography (OCT) provides an intriguing new method for monitoring coating thickness in commercial tablet manufacturing.
In recent years, tablet manufacturers have experimented with dynamic image analysis, spatial filter velocimetry, terahertz sensing, and near-infrared and Raman spectroscopy to assess the quality and thickness of tablet coatings.
While each of these methods has its own pros and cons, the search for the ideal, affordable in-line process analyzer has continued. The publication of a recent study on optical coherence tomography (OCT) and tablet coating offers a glimpse at one new possibility.
OCT utilizes interferometric imaging technology to produce depth-resolved, cross-sectional images of a tablet’s coating. These images are generated in real-time and don’t require further calibration or chemometric models to parse the data. In addition to the in-line data, OCT provides three-dimensional mapping to determine the quality of the applied coating (albeit off-line). Part of what makes this so intriguing is the potential for scaleup—the inline measurement potential of OCT expands well beyond lab-scale and into a viable possibility for commercial tablet manufacturing.
As with all new technologies, though, OCT does have its limitations. While it accurately pinpointed the endpoint in manufacturing processes for coatings ranging in thickness from 10 µm up to 100 µm, it could not monitor coatings thinner than 10 µm.
OCT also proved ineffective in measuring the thickness of coatings that contained pigments such as iron oxide or titanium dioxide, which severely limits its cosmetic application. Further development is clearly necessary for OCT to reach its full potential as a PAT (process analytical technology) tool, but even in its early stages it shows exciting potential.
The future of commercial tablet manufacturing relies on a deeper understanding of coating processes.
The methodologies behind the modern tablet date back millennia, but the future of the industry lies in fine-tuning such fundamentals as the coating processes. The quest for absolute accuracy and consistency is a moving target, but by adopting best practices and monitoring innovative approaches we can produce better, more consistent results than ever before.
