| 1. |
- Bonmann, Marlene, 1988, et al.
(författare)
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Terahertz radar observes powder dynamics for pharmaceutical manufacturing
- 2024
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Ingår i: IEEE Sensors Journal. - 1558-1748 .- 1530-437X. ; 24:13, s. 20512-20522
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Tidskriftsartikel (refereegranskat)abstract
- The optical opaqueness of powders has precluded the observation of powder flow dynamics in processing tubes, with important implications, for example, in the pharmaceutical industry, where non-destructive monitoring during the manufacturing process is essential to ensure the quality of the final product and the effectiveness of the process. Taking advantage of the high penetration of terahertz electromagnetic waves in powders and its wavelength-to-particle size ratio, we demonstrate that a submillimeter-wave pulse-Doppler radar can overcome the present challenges and characterize powder flow dynamics in pharmaceutical manufacturing processes. Mimicking typical vessel shapes in pharmaceutical operations, we were able to characterize falling powder streams in a tube with a sample volume resolution of a few cubic centimeters and a range resolution of about 5 mm. We successfully monitored particle velocity, particle distribution within the tube, and mass flow rate in real-time. This remote sensing method, based on advanced terahertz electronics, opens up the possibility to study and monitor powder dynamics in a wide range of applications.
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| 2. |
- Moradikouchi, Anis, 1990, et al.
(författare)
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Monitoring the Porosity of Pharmaceutical Tablets Using THz Frequency Domain Spectroscopy
- 2021
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, terahertz frequency domain spectroscopy (THz-FDS) in transmission mode has been employed to study the impact of design parameters of tablets such as initial particle size, drug concentration and compaction force, on their porosity. The complex transmission coefficient S21 of 69 tablets were measured using a vector network analyzer in the frequency range of 500-750 GHz. The results show that excipient particle size and compaction force have significant effects on the pore structure of the tablets and THz-FDS reveals to be a very promising tool in monitoring the porosity of pharmaceutical tablets.
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| 3. |
- Moradikouchi, Anis, 1990, et al.
(författare)
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Non-Destructive Characterization Of Pharmaceutical Tablets Using Terahertz Frequency Domain Spectroscopy
- 2019
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Ingår i: International Conference on Infrared, Millimeter, and Terahertz Waves, IRMMW-THz. - 2162-2027 .- 2162-2035. ; 2019-September
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Konferensbidrag (refereegranskat)abstract
- In this paper, terahertz frequency domain spectroscopy (THz-FDS) in transmission mode is used to study the influence of porosity on effective permittivity in pharmaceutical tablets. Three sets of training tablets with different dielectric constants were generated using microcrystalline cellulose (MCC), Benzophenone and Succinic acid. In each set, various compaction forces have been applied to the powders to produce tablets with different porosity. The results show that the extracted effective permittivity is sensitive to the change of porosity in tablets. Moreover, the results confirm that THz-FDS is able to differentiate between tablets with different dielectric constant and a linear correlation between effective permittivity and tablet density is observed. Therefore, THz-FDS technique is shown to be a promising technique for quality inspection of pharmaceutical tablets. © 2019 IEEE.
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| 4. |
- Moradikouchi, Anis, 1990, et al.
(författare)
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Small Variation of Active Pharmaceutical Ingredient Concentration Can Be Observed with THz Frequency Domain Spectroscopy
- 2021
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Ingår i: International Conference on Infrared, Millimeter, and Terahertz Waves, IRMMW-THz. - 2162-2027 .- 2162-2035. ; 2021-August
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Konferensbidrag (refereegranskat)abstract
- Terahertz frequency-domain spectroscopy (THz-FDS) has been employed to study the result of the variation of active pharmaceutical ingredients (API) on the effective refractive index of pharmaceutical tablets. A quasi-optical set-up with four off-axis parabolic mirrors was used to measure the effective refractive index of tablets in the frequency range of 500-750 GHz. It was observed that a small variation in API concentration can be detected using accurate measurements of the complex transmission coefficients. As a result, THz-FDS reveals to be an effective technique in monitoring the physical properties of pharmaceutical tablets
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| 5. |
- Moradikouchi, Anis, 1990, et al.
(författare)
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Terahertz Frequency-Domain Sensing Combined with Quantitative Multivariate Analysis for Pharmaceutical Tablet Inspection
- 2023
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 632
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Tidskriftsartikel (refereegranskat)abstract
- Near infrared (NIR) and Raman spectroscopy combined with multivariate analysis are established techniques for the identification and quantification of chemical properties of pharmaceutical tablets like the concentration of active pharmaceutical ingredients (API). However, these techniques suffer from a high sensitivity to particle size variations and are not ideal for the characterization of physical properties of tablets such as tablet density. In this work, we have explored the feasibility of terahertz frequency-domain spectroscopy, with the advantage of low scattering effects, combined with multivariate analysis to quantify API concentration and tablet density. We studied 33 tablets, consisting of Ibuprofen, Mannitol, and a lubricant with API concentration and filler particle size as the design factors. The terahertz signal was measured in transmission mode across the frequency range 750 GHz to 1.5 THz using a vector network analyzer, frequency extenders, horn antennas, and four off-axis parabolic mirrors. The attenuation spectral data were pre-processed and orthogonal partial least square (OPLS) regression was applied to the spectral data to obtain quantitative prediction models for API concentration and tablet density. The performance of the models was assessed using test sets. While a fair model was obtained for API concentration, a high-quality model was demonstrated for tablet density. The coefficient of determination (?2) for the calibration set was 0.97 for tablet density and 0.98 for API concentration, while the relative prediction errors for the test set were 0.7% and 6% for tablet density and API concentration models, respectively. In conclusion, terahertz spectroscopy demonstrated to be a complementary technique to Raman and NIR spectroscopy, which enables the characterization of physical properties of tablets like tablet density, and the characterization of API concentration with the advantage of low scattering effects.
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| 6. |
- Moradikouchi, Anis, 1990, et al.
(författare)
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Terahertz Frequency Domain Sensing for Fast Porosity Measurement of Pharmaceutical Tablets
- 2022
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 618
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Tidskriftsartikel (refereegranskat)abstract
- Porosity is an important property of pharmaceutical tablets since it may affect tablet disintegration, dissolution, and bio-availability. It is, therefore, essential to establish non-destructive, fast, and compact techniques to assess porosity, in-situ, during the manufacturing process. In this paper, the terahertz frequency-domain (THz-FD) technique was explored as a fast, non-destructive, and sensitive technique for porosity measurement of pharmaceutical tablets. We studied a sample set of 69 tablets with different design factors, such as particle size of the active pharmaceutical ingredient (API), Ibuprofen, particle size of the filler, Mannitol, API concentration, and compaction force. The signal transmitted through each tablet was measured across the frequency range 500-750 GHz using a vector network analyzer combined with a quasi-optical set-up consisting of four off-axis parabolic mirrors to guide and focus the beam. We first extracted the effective refractive index of each tablet from the measured complex transmission coefficients and then translated it to porosity, using an empirical linear relation between effective refractive index and tablet density. The results show that the THz-FD technique was highly sensitive to the variations of the design factors, showing that filler particle size and compaction force had a significant impact on the effective refractive index of the tablets and, consequently, porosity. Moreover, the fragmentation behavior of particles was observed by THz porosity measurements and was verified with scanning electron microscopy of the cross-section of tablets. In conclusion, the THz-FD technique, based on electronic solutions, allows for fast, sensitive, and non-destructive porosity measurement that opens for compact instrument systems capable of in-situ sensing in tablet manufacturing.
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| 7. |
- Moradikouchi, Anis, 1990, et al.
(författare)
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Terahertz radar sensing for real-time monitoring of powder streams
- 2023
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Ingår i: International Conference on Infrared, Millimeter, and Terahertz Waves, IRMMW-THz. - 2162-2027 .- 2162-2035.
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Konferensbidrag (refereegranskat)abstract
- In pharmaceutical manufacturing processes, the flow properties of powder streams moving in the manufacturing pipes directly impact the properties of the final drug product, and there is a need for real-time non-invasive monitoring of the powder flow properties with process analytical tools. In this study, we propose a frequency-modulated continuous wave (FMCW) Doppler radar system with a center frequency of 340 GHz to measure the flow properties of falling powder streams in a vertical transparent tube. We successfully measured the velocity profile and powder flow density variation along the height of the tube with a spatial resolution of about 5 mm. In conclusion, the terahertz FMCW Doppler radar system was shown to be highly promising for real-time sensing of flow properties of powder streams in the pharmaceutical manufacturing processes.
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| 8. |
- Moradikouchi, Anis, 1990
(författare)
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Terahertz sensing for non-destructive characterisation of pharmaceutical tablets
- 2022
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The pharmaceutical industry is shifting from conventional batch manufacturing to continuous manufacturing. To realise continuous manufacturing, it is crucial to assess the product quality of tablets at different stages of the production line. Therefore, there is a high need for quality control methods that are fast, non-destructive, and compact, with the possibility of implementation in the production line for real-time measurements. However, traditional quality control methods are typically slow and destructive. In our work, we propose the terahertz frequency domain (THz-FD) technique, based on all-electronic solutions, as a fast, sensitive, and non-destructive sensing technique with miniaturization capabilities for a future compact sensing system. In this technique, the effective refractive index of tablets at the terahertz frequency range is extracted from the transmission measurements of the scattering parameters of the tablets using a vector network analyser. Then, the effective refractive index is transferred to tablet density by using an empirical model and later is translated to tablet porosity. The measurement results show that the THz-FD technique could differentiate tablets with different refractive index and detect and quantify the minute changes of tablet density and porosity with the variation of design parameters. The design parameters were compaction force during tableting process, the concentration of the ingredients, and the particle size of the ingredients. It was observed that in our study the compaction force and filler particle size had the major impact on tablet porosity. In conclusion, it was demonstrated that the THz-FD technique based on electronic solutions allows for fast, sensitive, and non-destructive measurements of pharmaceutical tablets that open for compact instrument systems capable of in-line sensing in the tablet manufacturing process.
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| 9. |
- Moradikouchi, Anis, 1990
(författare)
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Terahertz sensing for pharmaceutical applications
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pharmaceutical tablets are manufactured through the compaction of powder blends or granules in batch or continuous processes. In continuous manufacturing, real-time assurance of quality becomes essential to ensure that the final product meets the quality standards approved by manufacturers and regulatory authorities. Process analytical methods used for real-time monitoring and control should be rapid, non-destructive, and suitable to be conducted in the manufacturing area. This thesis demonstrates the terahertz frequency domain (THz-FD) technique, based on all-electronic solutions, as a fast, sensitive, and non-destructive sensing technique, with the advantage of a reasonable compromise between deep penetration depth and high spatial resolution, high dynamic range, and miniaturization capabilities. In this study, the THz-FD technique was explored to monitor the key physical properties such as tablet density and porosity through effective refractive index using a vector network analyser. In addition, taking advantage of the lower scattering effect of the THz region compared to higher frequencies, the feasibility of terahertz frequency domain spectroscopy (THz-FDS) combined with multivariate analysis to quantify drug content and tablet density was explored. As the quality of the tablets is highly impacted by the powder flow during manufacturing processes, it is beneficial to build quality assurance before the tableting process. In the last study, the capability of a terahertz frequency-modulated continuous wave (FMCW) radar was for the first time explored to characterise the powder flow dynamics in manufacturing processes. The velocity and density variations of falling powder streams in a vertical tube were non-invasively measured, using a 340-GHz radar instrument with a deep penetration depth through the powder flow and a sample volume resolution in the order of a few cubic centimeters. In conclusion, it was demonstrated that the THz-FD technique and terahertz FMCW radar are highly promising as non-invasive process analytical tools for real-time quality monitoring of pharmaceutical powders and tablets.
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| 10. |
- Nefedova, Irina, et al.
(författare)
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Design of a quasioptical test bench for VNA extenders
- 2020
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Ingår i: International Conference on Infrared, Millimeter, and Terahertz Waves, IRMMW-THz. - 2162-2027 .- 2162-2035. ; 2020-November, s. 552-553
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Konferensbidrag (refereegranskat)abstract
- The CAD design, simulated optical performance, and test measurements of a quasioptical test bench for VNA extenders are presented. The system allows straightforward integration of off axis parabolic mirrors and VNA extenders. The mirror orientation reduces aberrations and results suggest optical properties are close to what is expected with geometric ray tracing.
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