Pill Coating Measurements with Terahertz Time-Domain

Albert Redo-Sanchez ([email protected]) October 2012 Zomega Terahertz Corporation 15 Tech Valley Drive, Suite 102 East Greenbush, NY 12061, USA Zomega Terahertz Corporation - PROPRIETARY - DO NOT DISTRIBUTE WITHOUT PERMISSION Wednesday, October 24, 12

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Principle of Operation ๏ Each interface (change of refractive index) causes a reflection of the incident wave ๏ Pulses measured at different times correspond to the optical thickness of each reflecting interface ๏ Optical thickness, or delay Δd, is the product of the refractive index n and the real thickness d of the interface (factor 2 is due to roundtrip of the reflection)

2d*n = Δd

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Samples

Plastic coating

Impregnated hard coating

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Experimental Setup

Mini-Z HS in reflection geometry

Surface of pill has to be normal to incident beam

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Coating Properties Arginine capsule coating

๏ For arginine capsule, coating can be measured individually (narginine ~ 2) ๏ Terahertz Time-Domain Spectroscopy can be used to calculate the refractive index and attenuation or absorption of the material

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Waveforms Raw Waveforms

Deconvolved Waveforms

CLEAN deconvolution algorithm (Ref. 1,2) directly on time-domain waveforms recovers position of reflecting interfaces Arginine (ar): d = Δd/(2*n) = 459/(2*2) = 115 um B2: d = Δd/(2*n) = 816/(2*2) = 204 um (assuming nb2 = nar) Measured thickness for Arginine is 120 um -> discrepancy is 4% Zomega Terahertz Corporation - PROPRIETARY - DO NOT DISTRIBUTE WITHOUT PERMISSION Wednesday, October 24, 12

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Mini-Z Terahertz Time-Domain Spectrometer ๏ First portable THz spectrometer in the world ๏ Turn-key operation (no alignment, no complex setup) ๏ Ideal for application development ๏ Waveform rate up to 500 Hz (High speed model) ๏ Integrated design ๏ Transmission and reflection geometries ๏ Vibration tolerant ๏ Open architecture

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Fiber-Coupled (FICO) THz Time-Domain System ๏ Independent Tx and Rx heads ๏ Fast scanning up to 500 Hz ๏ Real-time spectroscopy ๏ Broadband sensitivity up to 3 THz and high dynamic range ๏ Transmission and reflection geometries ๏ Several lens options to accommodate a variety of imaging conditions ๏ Measurement point indicated by laser guide for precise alignment

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Features/Benefits

๏ Non-contact inspection method ๏ Penetrates most coatings (stand alone and impregnated) ๏ Layer information via pulse analysis requires deconvolution to extract interfaces ๏ Measures refractive index and absorption properties of coatings with independent measurements ๏ Real-time operation is possible (500 waveforms per second)

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References

1. Högbom, J. A. (1974). Aperture synthesis with a non-regular distribution of interferometer baselines. Astronomy and Astrophysics Supplement Series, 15, 417–426 2. CLEAN algorithm: http://www.cv.nrao.edu/~abridle/deconvol/node7.html 3. Zeitler, J. A., Shen, Y., Baker, C., Taday, P. F., Pepper, M., & Rades, T. (2007). Analysis of coating structures and interfaces in solid oral dosage forms by three dimensional terahertz pulsed imaging. Journal of Pharmaceutical Sciences, 96(2), 330–340 4. May, R. K., Evans, M. J., Zhong, S., Warr, I., Gladden, L. F., Shen, Y., & Zeitler, J. A. (2011). Terahertz In-Line Sensor for Direct Coating Thickness Measurement of Individual Tablets During Film Coating in Real-Time. Journal of Pharmaceutical Sciences, 100(4), 1535–1544 5. Spencer, J. A., Gao, Z., Moore, T., Buhse, L. F., Taday, P. F., Newnham, D. A., et al. (2008). Delayed release tablet dissolution related to coating thickness by terahertz pulsed image mapping. Journal of Pharmaceutical Sciences, 97(4), 1543–1550

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