Bow-Tie Plasmonic Arrays Loaded with Graphene for the Fast Room Temperature Detection of Terahertz Quantum Cascade Lasers

Riccardo Degl'Innocenti ; Long Xiao ; David Jessop ; Stephen Kindness ; Christian W. Sol ; Yuan Ren ; Hungyen Lin ; Axel J. Zeitler ; Philipp Braeuninger-Weimer ; Stephan Hofmann ; Harvey Beere ; David Ritchie

Abstract:

We present a fast room temperature terahertz detector based on interdigitated bow-tie antennas asymmetrically doping and contacting graphene. The device was tested with a 2 THz quantum cascade laser yielding a responsivity of 0.5 μAW^-1.

Full article available here.

Evaluation of critical process parameters for inter-tablet coating uniformity of active-coated GITS using Terahertz Pulsed Imaging

Daniela Brock, J. Axel Zeitler, Adrian Funke, Klaus Knop, Peter Kleinebudde

Abstract

The aim of this study was the evaluation of critical process parameters (CPP) for inter-tablet coating uniformity in an active pan coating process using nondestructive Terahertz Pulsed Imaging (TPI). Coating uniformity was assessed by calculating the coefficient of variation (CV) of coating thickness measured by TPI, and the CV of API content measured by high performance liquid chromatography (HPLC). A design of experiments (DoE) was performed at pilot scale with drum load, drum speed, spray rate, run duration and spray pressure as factors. Good agreement in the CV of both analytical techniques was shown. The DoE models both revealed the same CPP: a low drum load, high drum speed, low spray rate and high run duration were beneficial for coating uniformity. The spray pressure was only significant in one of the DoE models. It was further shown that the negative impact of a high drum load on the CV cannot only be compensated by high drum speed, but also be compensated by a low spray rate and long run duration. It was demonstrated that TPI is a feasible tool for the measurement of inter-tablet coating uniformity and for the evaluation of CPP in an active pan coating process.

This study was performed using TeraView's Imaga 2000 system. (TeraView, Cambridge, UK)

Full Article: http://www.sciencedirect.com/science/article/pii/S0939641114002203

Terahertz Pulsed Imaging and Magnetic Resonance Imaging as Tools to Probe Formulation Stability

Qilei Zhang 1, Lynn F. Gladden 2, Paolo Avalle 3, J. Axel Zeitler 2;* and Michael D. Mantle 2

¹ Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China² Department of Chemical Engineering & Biotechnology, University of Cambridge, Cambridge CB2 3RA, UK³ Merck Sharp & Dohme Ltd., Hoddesdon EN11 9BU, UK

Abstract

Dissolution stability over the entire shelf life duration is of critical importance to ensure the quality of solid dosage forms. Changes in the drug release profile during storage may affect the bioavailability of drug products. This study investigated the stability of a commercial tablet (Lescolr XL) when stored under accelerated conditions (40 ^oC/75% r.h.). Terahertz pulsed imaging (TPI) was used to investigate the structure of the tablet coating before and after the accelerated aging process. The results indicate that the coating was reduced in thickness and exhibited a higher density after being stored under accelerated conditions for four weeks. In situ magnetic resonance imaging (MRI) of the water penetration processes during tablet dissolution in a USP-IV dissolution cell equipped with an in-line UV-vis analyzer was carried out to study local differences in water uptake into the tablet matrix between the stressed and unstressed state. The drug release profiles of the Lescolr XL tablet before and after the accelerated storage stability testing were compared using a “difference” factor ∫1 and a “similarity” factor ∫2. The results reveal that even though the physical properties of the coating layers changed significantly during the stress testing, the coating protected the tablet matrix and the densification of the coating polymer had no adverse effect on the drug release performance.

The TPI studies were performed using TeraView's TPI imaga 2000 system (TeraView, Cambridge, UK) 
Original Article:   http://www.mdpi.com/1999-4923/5/4/591

Application of terahertz pulsed imaging to analyse film coating characteristics of sustained-release coated pellets

• M. Haaser^a, b, c, 
• Y. Karrout^d, 
• C. Velghe^d, 
• Y. Cuppok^d, 
• K.C. Gordon^e, 
• M. Pepper^c, f, 
• J. Siepmann^d, 
• T. Rades^a, g, , , 
• P.F. Taday^c, 
• C.J. Strachan^a, h

• ^a School of Pharmacy, University of Otago, Dunedin, New Zealand
• ^b Cavendish Laboratories, University of Cambridge, Cambridge, United Kingdom
• ^c TeraView Ltd., Cambridge, United Kingdom
• ^d College of Pharmacy, Université Lille Nord de France, Lille, France
• ^e Department of Chemistry and MacDiarmid Institute, University of Otago, Dunedin, New Zealand
• ^f Department of Electronic Engineering, University College London, London, United Kingdom
• ^g Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
• ^h Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
• • http://dx.doi.org/10.1016/j.ijpharm.2013.05.039, How to Cite or Link Using DOI

 Abstract

Terahertz pulsed imaging (TPI) was employed to explore its suitability for detecting differences in the film coating thickness and drug layer uniformity of multilayered, sustained-release coated, standard size pellets (approximately 1 mm in diameter). Pellets consisting of a sugar starter core and a metoprolol succinate layer were coated with a Kollicoat^® SR:Kollicoat^® IR polymer blend for different times giving three groups of pellets (batches I, II and III), each with a different coating thickness according to weight gain. Ten pellets from each batch were mapped individually to evaluate the coating thickness and drug layer thickness between batches, between pellets within each batch, and across individual pellets (uniformity). From the terahertz waveform the terahertz electric field peak strength (TEFPS) was used to define a circular area (approximately 0.13 mm²) in the TPI maps, where no signal distortion was found due to pellet curvature in the measurement set-up used. The average coating thicknesses were 46 μm, 71 μm and 114 μm, for batches I, II and III respectively, whilst no drug layer thickness difference between batches was observed. No statistically significant differences in the average coating thickness and drug layer thickness within batches (between pellets) but high thickness variability across individual pellets was observed. These results were confirmed by scanning electron microscopy (SEM). The coating thickness results correlated with the subsequent drug release behaviour. The fastest drug release was obtained from batch I with the lowest coating thickness and the slowest from batch III with the highest coating thickness. In conclusion, TPI is suitable for detailed, non-destructive evaluation of film coating and drug layer thicknesses in multilayered standard size pellets.

...Samples were measured on a TPI imaga 2000 (Teraview Ltd., Cambridge, UK).

You can download the article on ScienceDirect

• 
  

Non-destructive measurement of polymer coatings on pharmaceutical tablets using X-ray micro CT and terahertz pulsed imaging

Authors: Isabelle-Sophie Russe^1,2, Daniela Brock^1,2, Klaus Knop², Peter Kleinebudde², J. Axel Zeitler¹⁼
1 Department of Chemical Engineering and Biotechnology, University of Cambridge,  Cambridge, UK
2 Institute of Pharmaceutics and Biopharmaceutics, University of Duesseldorf, Duesseldorf, Germany


Full text: http://www.skyscan.be/company/UM2013/15.pdf

Conclusion

We conclude that TPI is a robust technique, and, that due to its very simple measurement  principle, it is an ideal measurement technique to quantify the coating thickness in process control and quality monitoring applications. The method introduced in this paper will be useful to explore whether there is an influence on  the refractive index of a given coating formulation with changes in process conditions during  coating or curing. It furthermore opens the possibility, in pharmaceutical applications and  beyond, to develop metrology standards for coatings that can be used to calibrate TPI  measurements for absolute thickness.
Beyond its use as a calibration technique for TPI the XµCT method has provided some  intriguing insight into the coating properties at extremes of the tablet geometry, at the edges  of tablets where high curvature was thought to typically prevent quantitative TPI  measurements due to strong scattering. The main limitations of the XµCT technique are the  measurement, and in particular, processing time together with the high demands in  computational power and data storage as well as the limited contrast that can be resolved  between coating and core. We therefore envisage that the main impact of this technique is likely to be in research and development and to support techniques such as TPI rather than  in routine quality control or process measurements.

...Samples were measured on a TPI imaga 2000 (Teraview Ltd., Cambridge, UK), using a point spacing grid of 200 x 200 µm and a penetration depth of 1 mm in air...