Understanding pharmaceutical film coating process using combined optical coherence tomography and terahertz in-line sensing

Functional coatings are highly engineered drug delivery systems whose structure and composition are critical to the controlled release of the active pharmaceutical ingredient in the human body. These products are at the high value end of the market and represent sophisticated solutions to difficult disease management. Manufacturing these products is challenging largely because pharmaceutical processing is complex that has traditionally been dominated by empirical understanding. The increase in manufacturing complexity coincides with the paradigm shift that the pharmaceutical industry is facing today where emphasis is now being placed on fostering a greater product and manufacturing understanding for building quality into the product and enable continuous manufacturing. Building on the recent successful demonstration of combined optical coherence tomography and terahertz real-time sensing for a coating process where an unprecedented level of in-process diagnostic information were obtained, we will now perform systematic coating process investigation to quantify and model the effects of the key process parameters. The developed data-driven models will in turn allow us to identify the optimal process conditions for validation against science-based process modelling, which can then be used to explain process observations. Ultimately, enhanced process understanding will enable the development of model-based predictive control for the full implementation of continuous manufacturing for producing next generation pharmaceutical products. This project will be supported by a world leading supplier of manufacturing equipment (Bosch, Germany), academic technology collaborators (University of Cambridge, UK and University of Liverpool, UK) and coating materials suppliers (BASF, UK and Colorcon, UK).

Pharmaceutical film coatings serve the very purpose of protecting the active ingredient from light and moisture, thereby improving the shelf-life of the dosage forms. Coatings can also serve the purpose of improving the aesthetics and taste masking. For advanced dosage forms, coatings serve a functional purpose as in the case of active coating or it can be used to control drug release, thereby determining the therapeutic efficacy of the drug. The lack of fundamental process understanding currently hinders the production of advanced dosage forms on a consistent quality basis. An improved process understanding will have an immediate impact on coating equipment manufacturers by suggesting possible design changes to enhance coating efficiency. It would also recommend methods of deploying process analytical technologies for process monitoring. Process understanding will also impact pharmaceuticals and coating materials suppliers, in terms of optimising process and control leading to reduced waste and improved product performance. The interdisciplinary nature of the project will expose the industry to cutting-edge process analytical technologies, novel methods of data interpretation and modelling, while at the same time, provide an unique opportunity for young researchers to work at the forefront of pharmaceutical science and process analytical technologies, and to develop advanced skills that are essential for UK research and business. This research will therefore be supported by a world leading coating equipment manufacturer (Bosch, Germany) and coating materials suppliers (BASF, UK and Colorcon, UK). At an industry wide level, this work will generate a substantial body of new academic knowledge that coincides timely with the paradigm shift that the pharmaceutical industry is facing today as it moves from the traditional quality by testing to quality by design, where the focus is on product and manufacturing understanding. The knowledge gained would in turn inform the regulators on the best practices. In the longer term, this work would enable the development of active control strategies as part of the full implementation of continuous manufacturing in order to facilitate the production of advanced dosage forms on a consistent quality level basis efficiently. This would in turn have impact across a very wide range of communities both economically and societally, especially as these dosage forms represent sophisticated solutions to difficult disease management.