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

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Terahertz In-Line Sensor for Direct Coating Thickness Measurement of Individual Tablets during Film Coating in Real-Time

ROBERT K. MAY, MICHAEL J. EVANS, SHUNCONG ZHONG,  IAN WARR, LYNN F. GLADDEN, YAOCHUN SHEN,  J. AXEL ZEITLER

J Pharm Sci 100:1535–1544, 2011

http://onlinelibrary.wiley.com/doi/10.1002/jps.22359/abstract

ABSTRACT:

We present a new in-line measurement technique to determine the coating thickness of individual pharmaceutical tablets during film coating in a pan coating unit using pulsed terahertz technology. Results of these real-time terahertz measurements acquired during a production scale coating run are validated using both off-line high-resolution terahertz pulsed imaging of the whole dosage form as well as weight-gain measurements made on sample tablets removed at discrete time intervals during the process run. The terahertz measurements provide a direct method of determining the coating thickness, and no chemometric calibration models are required for the quantification. The results, and their repeatability, demonstrate that real-time monitoring of pharmaceutical tablet coating is not only possible but also provides substantially more information of the coating quality than the standard quality control method. Rather than providing the average coating thickness of a large number of tablets, the terahertz sensor provides the thickness of up to 100 individual tablet coatings per minute. Using this information, the operator can get additional information about the thickness distribution in the coating pan and adjust the process accordingly. At present, a minimum coating thickness of 40 µm is required to determine the coating thickness. The technique is applicable for coatings up to 1mm in thickness. Within that range, it provides thickness measurements of sub-micron resolution. Terahertz in-line coating process measurements show considerable potential for applications in real-time release, process analytical technology and quality by design.

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Prediction of dissolution time and coating thickness of sustained release formulations using Raman spectroscopy and terahertz pulsed imaging

·         European Journal of Pharmaceutics and Biopharmaceutics

Available online 5 January 2012

• Joshua Müller^a, 
• Daniela Brock^a, 
• Klaus Knop^a, 
• J. Axel Zeitler^b, 
• Peter Kleinebudde

• Abstract

  Raman spectroscopy was implemented successfully as a non-invasive and rapid process analytical technology (PAT) tool for in-line quantitative monitoring of functional coating. Coating experiments were performed at which diprophylline tablets were coated with a sustained release formulation based on Kollicoat® SR 30 D. Using PLS a multivariate model was constructed by correlating Raman spectral data with the mean dissolution time as determined by dissolution testing and the coating thickness as measured by terahertz pulsed imaging.
  By performing in-line measurements it was possible to monitor the progress of the coating process and to detect the end point of the process, where the acquired coating amount was achieved for the desired MDT or coating thickness.
  
  Mean dissolution time (MDT) over coating time predicted by Raman spectroscopy (top left) and in correlation to coating thickness measured by terahertz spectroscopy (top right). Layer thickness maps and histograms from TPI measurements after a short (left) and a longer (right) coating time.
  
  
  Terahertz results were acquired on a TeraView's TPI2000 instrument.
  
  
  For more information :
  http://www.sciencedirect.com/science/article/pii/S0939641111003614
  
  

  Keywords

  • Process analytical technology; 
  • Multivariate data analysis; 
  • Raman spectroscopy; 
  • Terahertz pulsed imaging; 
  • Functional coating; 
  • Mean dissolution time