Shuncong Zhong

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

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 1 mm 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.

Hardness and Density Distributions of Pharmaceutical Tablets Measured by Terahertz Pulsed Imaging

We present terahertz pulsed imaging (TPI) as a novel tool to quantify the hardness and surface density distribution of pharmaceutical tablets. Good agreement between the surface refractive index (SRI) measured by TPI and the crushing force measured from diametral compression tests was found using a set of tablets that were compacted at various compression forces. We also found a strong correlation between TPI results and tablet bulk density, and how these relate to tablet hardness. Numerical simulations of tablet surface density distribution by finite element analysis exhibit excellent agreement with the TPI measured SRI maps. These results show that TPI has an advantage over traditional diametral compression and is more suitable for nondestructive hardness and density distribution monitoring and control of pharmaceutical manufacturing processes.

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

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.

Pharmaceutical tablet hardness measurements with thz pulsed imaging

We present the results of terahertz pulsed imaging (TPI) experiments to measure the ‘hardness’ of pharmaceutical solid dosage forms (tablets) compacted at various compression forces. Results of TPI measurements are compared to those from diametric compression tests as well as finite element analysis (FEA) simulations of density distributions on the surface of the tablet. In both cases strong correlation with TPI results was found. In particular, radially symmetric spatial distributions in tablet density due to the shape of the punch used in tablet manufacture were observed. The results of these experiments show that TPI is suitable for non-destructive monitoring and control of pharmaceutical manufacturing processes.

FDTD study of a novel terahertz emitter with electrical field enhancement using surface plasmon resonance

In this work, the flnite-difierence time-domain (FDTD) technique is used to study novel terahertz (THz) emitter structures. The proposed THz antenna requires less pump power of the femtosecond laser pulse whilst provides higher THz output power. This is achieved by the enhancement of the localized electric fleld in the THz emitter This electric fleld enhancement is found to have two origins: One is owing to the enhancement of the static electric fleld of the bias voltage, and the other is the enhancement of the electric fleld of the incoming femtolaser pulse. The latter enhancement is caused by the interaction of the pump laser and the surface plasmon resonance at the conical gold structure of the photoconductive emitter. This new terahertz emitter could lead to new applications where high-power and broadband terahertz sources are needed.

Compressed terahertz imaging system using a spin disk

We report the development of a terahertz imaging system based on the concept of compressive sensing. A spin disk with random patterns was used to modulate the terahertz beam, and terahertz image was subsequently reconstructed from the measured terahertz signals. We present experimental results obtained using both a BWO source at 0.14 THz and a thermal light source (blackbody radiation) covering both infrared and visible range.

Terahertz pulsed imaging of surface variations on pharmaceutical tablets

We present an analysis of terahertz pulsed imaging (TPI) measurements made on pharmaceutical tablets compacted at a range of compression forces. In particular, we investigate the uniformity and local variations in the refractive index on the surface of tablets of different shapes. Through terahertz imaging it has been possible to observe small-scale deviations on tablet surfaces that may have relevance to the quality of tablet manufacture and performance.

Noninvasive 3D characterization of layered samples using terahertz pulsed imaging and infrared optical coherence tomography

Terahertz pulsed imaging (TPI) and Optical Coherence Tomography (OCT) are two powerful techniques allowing high quality three-dimensional images from within scattering media to be obtained noninvasively. In this paper, we report experimental results of using TPI and OCT for characterizing layered samples including pharmaceutical coatings. We found that infrared OCT provides better axial resolutions whilst TPI is less prone to scattering problems thus is well suited for characterizing pharmaceutical tablet coatings.

Graphene/Insulator Stack Based Ultrasensitive Terahertz Sensor With Surface Plasmon Resonance

We proposed a terahertz (THz) surface plasmon resonance (SPR) sensor with Kretschmann coupling configuration with buffer layer covered substrate containing doped monolayer graphene (MLG) directly deposited onto the coupling prism. The performance of the SPR sensor in terms of detection accuracy, sensitivity and figure of merit (FOM) were investigated by applying angular interrogation technique. The results demonstrated that the prism/substrate/graphene coupling structure has higher detection accuracy after coating a low-permittivity buffer layer underneath graphene. Moreover, the sensitivity of sensor could be enhanced using larger refractive index substrate. Furthermore, this proposed structure could effectively overcome the challenge that sample preparation with a small thickness needs to be maintained in Otto geometry based sensor. The results showed the maximum sensitivity of the THz plasmonic sensor up to 49.5 deg/RIU along with a FOM of 8.76 RIU-1. The prominent characteristics of the proposed structure would pave the way for high-performance THz plasmonic sensors.

Performance analysis of higher mode spoof surface plasmon polariton for terahertz sensing

We investigated the spoof surface plasmon polaritons (SSPPs) on 1D grooved metal surface for terahertz sensing of refractive index of the filling analyte through a prism-coupling attenuated total reflection setup. From the dispersion relation analysis and the finite element method-based simulation, we revealed that the dispersion curve of SSPP got suppressed as the filling refractive index increased, which cause the coupling resonance frequency redshifting in the reflection spectrum. The simulated results for testing various refractive indexes demonstrated that the incident angle of terahertz radiation has a great effect on the performance of sensing. Smaller incident angle will result in a higher sensitive sensing with a narrower detection range. In the meanwhile, the higher order mode SSPP-based sensing has a higher sensitivity with a narrower detection range. The maximum sensitivity is 2.57 THz/RIU for the second-order mode sensing at 45° internal incident angle. The proposed SSPP-based method has great potential for high sensitive terahertz sensing.