9 research outputs found
Terahertz sensing for non-destructive characterisation of pharmaceutical tablets
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
Terahertz sensing for pharmaceutical applications
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
Terahertz Frequency Domain Sensing for Fast Porosity Measurement of Pharmaceutical Tablets
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
Terahertz Frequency-Domain Sensing Combined with Quantitative Multivariate Analysis for Pharmaceutical Tablet Inspection
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 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
Small Variation of Active Pharmaceutical Ingredient Concentration Can Be Observed with THz Frequency Domain Spectroscopy
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 tablet
Monitoring the Porosity of Pharmaceutical Tablets Using THz Frequency Domain Spectroscopy
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
Non-Destructive Characterization Of Pharmaceutical Tablets Using Terahertz Frequency Domain Spectroscopy
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\ua0a\ua0linear correlation between effective permittivity and tablet density is observed. Therefore, THz-FDS technique is shown to be\ua0a\ua0promising technique for quality inspection of pharmaceutical tablets. \ua9 2019 IEEE
Design of a quasioptical test bench for VNA extenders
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.Peer reviewe
THz Frequency Quantification of Water Gradients in Drying Paper
THz-reflection spectroscopy was used to extract time-varying water gradients in drying paper targets mounted on electrically thick dielectric substrates. The data showed a pronounced and prolonged drop below dry reflectivity when the water content that peaks at low weight (∼10%). A binomial distribution fitted to the acquired data confirms the existence of the time-varying water content gradient and suggests aqueous thin film hydration can be quantified even when the contrast between the film and backing material is low.Peer reviewe