Abstract-Review of Terahertz Pulsed Imaging for Pharmaceutical Film Coating Analysis

Décio Alves-Lima, Jun Song. Xiaoran Li, Alessia Portieri, Yaochun Shen, J. Axel Zeitler, Hungyen Lin

https://www.mdpi.com/1424-8220/20/5/1441

Terahertz pulsed imaging (TPI) was introduced approximately fifteen years ago and has attracted a lot of interest in the pharmaceutical industry as a fast, non-destructive modality for quantifying film coatings on pharmaceutical dosage forms. In this topical review, we look back at the use of TPI for analysing pharmaceutical film coatings, highlighting the main contributions made and outlining the key challenges ahead

Abstract-Through-substrate terahertz time-domain reflection spectroscopy for environmental graphene conductivity mapping

Applied Physics Letters

 Hungyen Lin,  Oliver J. Burton, Sebastian Engelbrecht, Kai-Henning Tybussek,  Bernd M. Fischer,  Stephan Hofmann

Schematic of the reflection-based THz-TDS to measure the complex conductivity of graphene through the substrate in a nitrogen purge environment.

https://aip.scitation.org/doi/abs/10.1063/1.5135644

We demonstrate how terahertz time-domain spectroscopy (THz-TDS) operating in reflection geometry can be used for quantitative conductivity mapping of large area chemical vapor deposited graphene films through silicon support. We validate the technique against measurements performed using the established transmission based THz-TDS. Our through-substrate approach allows unhindered access to the graphene top surface and thus, as we discuss, opens up pathways to perform in situ and in-operando THz-TDS using environmental cells.

H.L. acknowledges financial support from the EPSRC (Grant No. EP/R019460/1). S.H. acknowledges funding from the EPSRC (Grant No. EP/K016636/1, GRAPHTED). We also thank Dr. Philipp Braeuninger-Weimer for useful discussion. Additional data for this article are available at https://doi.org/10.17635/lancaster/researchdata/336.

Abstract-A quantitative comparison of in-line coating thickness distributions obtained from a pharmaceutical tablet mixing process using discrete element method and terahertz pulsed imaging

Chunlei Pei, Hungyen Lin, Daniel Markl, Yao-ChunShen, J.Axel Zeitler, James A.Elliott,

https://www.sciencedirect.com/science/article/pii/S0009250918304172

The application of terahertz pulsed imaging (TPI) in the in-line configuration to monitor the coating thickness distribution of pharmaceutical tablets has the potential to improve the performance and quality of the spray coating process. In this study, an in-line TPI method is used to measure coating thickness distributions on pre-coated tablets during mixing in a rotating pan, and compared with results obtained numerically using the discrete element method (DEM) combined with a ray-tracing technique. The hit rates (i.e. the number of successful coating thickness measurements per minute) obtained from both terahertz in-line experiments and the DEM/ray-tracing simulations are in good agreement, and both increase with the number of baffles in the mixing pan. We demonstrate that the coating thickness variability as determined from the ray-traced data and the terahertz in-line measurements represents mainly the intra-tablet variability due to relatively uniform mean coating thickness across tablets. The mean coating thickness of the ray-traced data from the numerical simulations agrees well with the mean coating thickness as determined by the off-line TPI measurements. The mean coating thickness of in-line TPI measurements is slightly higher than that of off-line measurements. This discrepancy can be corrected based on the cap-to-band surface area ratio of the tablet and the cap-to-band sampling ratio obtained from ray-tracing simulations: the corrected mean coating thickness of the in-line TPI measurements shows a better agreement with that of off-line measurements.

Abstract-Contactless graphene conductivity mapping on a wide range of substrates with terahertz time-domain reflection spectroscopy

Hungyen Lin, Philipp Braeuninger-Weimer, Varun S. Kamboj, David S. Jessop, Riccardo Degl’Innocenti, Harvey E. Beere, David A. Ritchie, J. Axel Zeitler,  Stephan Hofmann

https://www.nature.com/articles/s41598-017-09809-7?WT.feed_name=subjects_materials-science

We demonstrate how terahertz time-domain spectroscopy (THz-TDS) operating in reflection geometry can be used for quantitative conductivity mapping of large area chemical vapour deposited graphene films on sapphire, silicon dioxide/silicon and germanium. We validate the technique against measurements performed with previously established conventional transmission based THz-TDS and are able to resolve conductivity changes in response to induced back-gate voltages. Compared to the transmission geometry, measurement in reflection mode requires careful alignment and complex analysis, but circumvents the need of a terahertz transparent substrate, potentially enabling fast, contactless, in-line characterisation of graphene films on non-insulating substrates such as germanium.

Abstract-Fast room temperature detection of terahertz quantum cascade lasers with graphene loaded bow-tie plasmonic antenna arrays

Riccardo Degl'Innocenti, Long Xiao, David S. Jessop, Stephen J Kindness, Yuan Ren, Hungyen Lin, J. Axel Zeitler, Jack A. Alexander-Webber, Hannah J Joyce, Philipp Braeuninger-Weimer, Stephan Hofmann, Harvey E Beere, and David A. Ritchie

ACS Photonics, Just Accepted Manuscript

DOI: 10.1021/acsphotonics.6b00405

Publication Date (Web): September 20, 2016

Copyright © 2016 American Chemical Society

https://www.blogger.com/blogger.g?blogID=124073320791841682#editor/target=post;postID=4022381804460754923

We present a fast room temperature terahertz detector based on interdigitated bow-tie antennas contacting graphene. Highly efficient photodetection was achieved by using two metals with different work functions as the arms of a bow-tie antenna contacting graphene. Arrays of the bow-ties were fabricated in order to enhance the responsivity and coupling of the incoming light to the detector realizing an efficient imaging system. The device has been characterized and tested with a terahertz quantum cascade laser emitting in single frequency around 2 THz yielding a responsivity of ~ 34 μA/W and a noise-equivalent-power of ~1.5E-7W/Hz1/2

Abstract-Fast modulation of terahertz quantum cascade lasers using graphene loaded plasmonic antennas

Riccardo Degl'Innocenti, David S. Jessop, Christian W. O. Sol, Long Xiao, Stephen J. Kindness, Hungyen Lin, J. Axel Zeitler, Philipp Braeuninger-Weimer, Stephan Hofmann, Yuan Ren, Varun S. Kamboj, Jonathan P. Griffiths, Harvey E. Beere, and David A. Ritchie

ACS Photonics, Just Accepted Manuscript

DOI: 10.1021/acsphotonics.5b00672

Publication Date (Web): February 23, 2016

Copyright © 2016 American Chemical Society

http://pubs.acs.org/doi/abs/10.1021/acsphotonics.5b00672?journalCode=apchd5

We report the fast amplitude modulation of a quantum cascade laser emitting in single mode operation in the terahertz frequency range by employing compact, integrated devices based on the interplay between plasmonic antenna arrays and monolayer graphene. By acting on the carrier concentration of graphene the optical response of these plasmonic resonances was modified. The modulators characteristics have been studied by using both time domain spectroscopic laser systems, yielding the broad frequency response of these resonant arrays, and quantum cascade lasers, providing us with a narrow and stable laser source, a mandatory prerequisite for the determination of the modulation speed of these devices. The measured modulation speed exhibits a cut-off frequency of 5.5 MHz ± 1.1 MHz. These results represent the first step toward the realization of fast integrated circuitry for communications in the terahertz frequency range.

Abstract-Impact of processing conditions on inter‐tablet coating thickness variations measured by terahertz in-line sensing

Lin, Hungyen and May, Robert K. and Evans, Michael J. and Zhong, Shuncong and Gladden, Lynn F. and Shen, Yaochun and Zeitler, J. Axel 

http://strathprints.strath.ac.uk/53773/

A novel in-line technique utilising pulsed terahertz radiation for direct measurement of the film coating thickness of individual tablets during the coating process was previously developed and demonstrated on a production-scale coater. Here, we use this technique to monitor the evolution of tablet film coating thickness and its inter-tablet variability during the coating process under a number of different process conditions that have been purposefully induced in the production-scale coating process. The changes that were introduced to the coating process include removing the baffles from the coater, adding uncoated tablets to the running process, halting the drum, blockage of spray guns and changes to the spray rate. The terahertz sensor was able to pick up the resulting changes in average coating thickness in the coating drum and we report the impact of these process changes on the resulting coating quality.

Abstract-Quantifying pharmaceutical film coating with optical coherence tomography and terahertz pulsed imaging: an evaluation

Hungyen Lin,Yue Dong, Yaochun Shen, Axel J. Zeitler,
https://www.repository.cam.ac.uk/handle/1810/248408?show=full

Spectral domain optical coherence tomography (SD-OCT) has recently attracted a lot of interest in the pharmaceutical industry as a fast and non-destructive modality for quantification of thin film coatings that cannot easily be resolved with other techniques. Due to the relative infancy of this technique, much of the research to date has focused on developing the in-line measurement technique for assessing film coating thickness. To better assess OCT for pharmaceutical coating quantification, this paper evaluates tablets with a range of film coating thickness measured using OCT and terahertz pulsed imaging (TPI) in an off-line setting. In order to facilitate automated coating quantification for film coating thickness in the range of 30 to 200 μm, an algorithm that uses wavelet denoising and a tailored peak finding method is proposed to analysis each of the acquired A-scan. Results obtained from running the algorithm reveal an increasing disparity between the TPI and OCT measured intra-tablet variability when film coating thickness exceeds 100 μm. The finding further confirms that OCT is a suitable modality for characterising pharmaceutical dosage forms with thin film coatings while TPI is well suited for thick coatings.

Abstract- Impact of Processing Conditions on Inter-tablet Coating Thickness Variations Measured by Terahertz In-Line Sensing

1. Hungyen Lin¹, 
2. Robert K. May^1,†, 
3. Michael J. Evans², 
4. Shuncong Zhong^3,‡, 
5. Lynn F. Gladden¹, 
6. Yaochun Shen³ and
7. J. Axel 

1. http://onlinelibrary.wiley.com/doi/10.1002/jps.24503/abstract

Article first published online: 2 JUN 2015

DOI: 10.1002/jps.24503

© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association

A novel in-line technique utilising pulsed terahertz radiation for direct measurement of the film coating thickness of individual tablets during the coating process was previously developed and demonstrated on a production-scale coater. Here, we use this technique to monitor the evolution of tablet film coating thickness and its inter-tablet variability during the coating process under a number of different process conditions that have been purposefully induced in the production-scale coating process. The changes that were introduced to the coating process include removing the baffles from the coater, adding uncoated tablets to the running process, halting the drum, blockage of spray guns and changes to the spray rate. The terahertz sensor was able to pick up the resulting changes in average coating thickness in the coating drum and we report the impact of these process changes on the resulting coating quality. 

© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci

Abstract-Diffusion and Swelling Measurements in Pharmaceutical Powder Compacts Using Terahertz Pulsed Imaging

1. Samy Yassin, 
2. Ke Su, 
3. Hungyen Lin, 
4. Lynn F. Gladden and
5. J. Axel Zeitler^*

Article first published online: 2 FEB 2015

DOI: 10.1002/jps.24376

© 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association

http://onlinelibrary.wiley.com/doi/10.1002/jps.24376/abstract

Tablet dissolution is strongly affected by swelling and solvent penetration into its matrix. A terahertz-pulsed imaging (TPI) technique, in reflection mode, is introduced as a new tool to measure one-dimensional swelling and solvent ingress in flat-faced pharmaceutical compacts exposed to dissolution medium from one face of the tablet. The technique was demonstrated on three tableting excipients: hydroxypropylmethyl cellulose (HPMC), Eudragit RSPO, and lactose. Upon contact with water, HPMC initially shrinks to up to 13% of its original thickness before undergoing expansion. HPMC and lactose were shown to expand to up to 20% and 47% of their original size in 24 h and 13 min, respectively, whereas Eudragit does not undergo dimensional change. The TPI technique was used to measure the ingress of water into HPMC tablets over a period of 24 h and it was observed that water penetrates into the tablet by anomalous diffusion. X-ray microtomography was used to measure tablet porosity alongside helium pycnometry and was linked to the results obtained by TPI. Our results highlight a new application area of TPI in the pharmaceutical sciences that could be of interest in the development and quality testing of advanced drug delivery systems as well as immediate release formulations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci