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Terahertz Applications Group

Department of Chemical Engineering and Biotechnology

Studying at Cambridge

 

Pharmaceutics

Pharmaceutics, Coatings, Process Research

For pharmaceutical process research we apply terahertz radiation to non-destructively image film coatings and tablet surface density. By exploiting the short pulse duration and the ability to penetrate most polymers used as excipients for film coating we are able to spatially resolve the thickness and density of the coating over the surface of the tablet. Terahertz radiation can propagate more than 1 mm into the tablet and hence it is possible to measure through multiple coating layers without physically slicing the sample. Currently, one of our main interests is the development of online sensors which will allow the robust measurement of coating thickness in real-time in a film coating machine in situ.

The aim of our research activities in this field is to link the coating properties as measured by terahertz imaging with the drug release performance of the final dosage form. We use magnetic resonance imaging (MRI) along with other advanced techniques to interpret the terahertz results. Through the better understanding of the physical properties of the film coating and the tablet dissolution we open new opportunities for improved Process Analytical Technology (PAT) and Quality-by-Design (QbD).

Furthermore we develop novel sensor technology for particle size measurements and high speed tablet hardness testing.

Film Coating Characterisation

One of the biggest challenges for the pharmaceutical industry is to manufacture tablets with consistent quality. Existing measurement technologies struggle to provide the necessary process control. One aspect of our research applies terahertz radiation to non-destructively image film coatings and tablet surface density. By exploiting the short pulse duration and the ability to penetrate most polymers used as excipients for film coating, we are able to spatially resolve the thickness and density of the coating over the surface of the tablet.

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3D maps of coating layer thickness (top) and surface refractive index (bottom) for a biconvex tablet

Terahertz radiation can propagate more than 1 mm into the tablet and hence it is possible to measure through multiple coating layers without physically slicing the sample. Currently, we have developed a robust in-line system for quantitatively measure the coating thickness of randomly moving tablets in a pan coater. This development allows terahertz sensors to make their way from the development laboratory to the manufacturing floor.  

toc_tpi_thickness_3D.pngtoc_xmct_thickness_3D.png

The ultimate aim of our research activities in this field is to link the coating properties as measured by terahertz imaging with the drug release performance of the advanced dosage form. We closely collaborate with our colleagues at the MRRC to use magnetic resonance imaging (MRI) to interpret the terahertz results. Through the better understanding of the physical properties of the film coating and the tablet dissolution, we open new opportunities for improved process understanding for applications in Process Analytical Technology (PAT) and Quality-by-Design (QbD). 

tsb_sensor1.jpgin-line_sensor_prototype_photo.jpg

Key publications 

I.S. Russe, D. Brock, K. Knop, P. Kleinebudde and J.A. Zeitler, Validation of terahertz coating thickness measurements using X-ray microtomography, Molecular Pharmaceutics, doi:10.1021/mp300383y, 9,3551-3559 (2012).

R.K. May, M.J. Evans, S. Zhong, I. Warr, L.F. Gladden, Y.C. Shen and J.A. Zeitler, Terahertz in-line sensor for direct coating thickness measurement of individual tablets during film coating in real-time, Journal of Pharmaceutical Sciences, doi:10.1002/jps.22359, 100, 1535-1544 (2011).

L. Ho, R. Müller, M. Römer, K.C. Gordon, J. Heinämäki, P. Kleinebudde, M. Pepper, T. Rades, Y.C. Shen, C.J. Strachan, P.F. Taday, and J.A. Zeitler, The analysis of sustained-release tablet film coats using terahertz pulsed imaging, Journal of Controlled Release, doi:10.1016/j.jconrel.2007.03.011, 119, 253-261 (2007).

J.A. Zeitler, Y.C. Shen, C. Baker, P.F. Taday, M. Pepper, and T. Rades, Analysis of coating structures and interfaces in solid oral dosage forms by three dimensional terahertz pulsed imaging, Journal of Pharmaceutical Sciences, doi:10.1002/jps.20789, 96, 330-340 (2007).