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The need for wideband metamaterial absorbers (WBMA) for applications other than sensing and filtering has demanded modifications to the conventional three-layer metal-insulator-metal (MIM) absorber configuration. This modification often results in complex geometries and an increased number of layers requiring complex lithographic processes for fabrication. Here, we show that a metamaterial absorber with rectangular geometry in the simple MIM configuration can provide wideband absorption covering the ultraviolet and near-infrared spectral range. Due to its asymmetric nature, the WBMA is sensitive to the polarization of the incident light and independent of the angle of incidence up to about 45° depending on the polarization of the incident light. The characteristics of the WBMA presented here may be useful for applications such as detectors for wide spectral band applications.

There is a clear need for a robust process analytical technology tool that can be used for on-line/in-line prediction of dissolution and disintegration characteristics of pharmaceutical tablets during manufacture. Tablet porosity is a reliable and fundamental critical quality attribute which controls key mass transport mechanisms that govern disintegration and dissolution behavior. A measurement protocol was developed to measure the total porosity of a large number of tablets in transmission without the need for any sample preparation. By using this fast and non-destructive terahertz spectroscopy method it is possible to predict the disintegration and dissolution of drug from a tablet in less than a second per sample without the need of a chemometric model. The validity of the terahertz porosity method was established across a range of immediate release (IR) formulations of ibuprofen and indomethacin tablets of varying geometries as well as with and without debossing. Excellent correlation was observed between the measured terahertz porosity, dissolution characteristics (time to release 50% drug content) and disintegration time for all samples. These promising results and considering the robustness of the terahertz method pave the way for a fully automated at-line/on-line porosity sensor for real time release testing of IR tablets dissolution.

Investigating the liquid transport kinetics of solid catalysts is of great importance for gaining a better understanding of the manufacturing and performance of such catalysts during reaction upon contact with the liquid. Terahertz pulsed imaging (TPI) coupled with a newly designed flow cell was used to quantify the rate of water ingress into α-alumina pellets with a range of different porosities. A wide range of compaction forces (cold compaction, 7–58 kN) and sintering conditions (no firing and sintering at 1200 and 1300 °C) was investigated to explore the optimal pellet microstructure, i.e. mechanically strong but sufficiently porous for fast liquid transport kinetics. The results confirm that both the microstructure characteristics, particularly porosity, as well as the surface properties, i.e. wettability, influence the liquid transport kinetics. Fitting the TPI penetration rates with a power law shows that the type of observed mass transport characteristics is consistent with Darcy flow. The Lucas–Washburn equation was used to calculate the hydraulic radius based on the transport data. In summary, the results demonstrate that TPI has great potential to study the liquid transport kinetics of porous ceramic catalysts and catalyst supports and that can comfortably quantify transport processes at rates of 250 μm s−1 and beyond in such substrates for better quality control and optimised design and performance of such materials.

Porosity, one of the important quality attributes of pharmaceutical tablets, directly affects the mechanical properties, the mass transport and hence tablet disintegration, dissolution and ultimately the bioavailability of an orally administered drug. The ability to accurately and quickly monitor the porosity of tablets during manufacture or during the manufacturing process will enable a greater assurance of product quality. This tutorial systematically outlines the steps involved in the terahertz-based measurement method that can be used to quantify the porosity of a tablet within seconds in a non-destructive and non-invasive manner. The terahertz-based porosity measurement can be performed using one of the three main methods, which are (i) the zero-porosity approximation (ZPA); (ii) the traditional Bruggeman effective medium approximation (TB-EMA); and (iii) the anisotropic Bruggeman effective medium approximation (AB-EMA). By using a set of batches of flat-faced and biconvex tablets as a case study, the three main methods are compared and contrasted. Overall, frequency-domain signal processing coupled with the AB-EMA method was found to be most suitable approach in terms of accuracy and robustness when predicting the porosity of tablets over a range of complexities and geometries. This tutorial aims to concisely outline all the necessary steps, precautions and unique advantages associated with the terahertz-based porosity measurement method.

Terahertz time-domain spectroscopy (THz-TDS) is a novel technique which has been applied for pore structure analysis and porosity measurements. For this, mainly the anisotropic Bruggeman (AB-EMA) model is applied to correlate the effective refractive index (neff) of a tablet and the porosity as well as to evaluate the pore shape based on the depolarisation factor L. This paper investigates possible error sources of the AB-EMA for THz-TDS based tablet analysis. The effect of absorption and tablet anisotropy – changes of pore shape with porosity and density distribution – have been investigated. The results suggest that high tablet absorption has a negligible effect on the accuracy of the AB-EMA. In regards of tablet anisotropy the accuracy of the porosity determination is not impaired significantly. However, density distribution and variations in the pore shape with porosity resulted in an unreliable extraction of the tablet pore shape. As an extension of the AB-EMA a new concept was introduced to convert the model into bounds for L. This new approach was found useful to investigate tablet pore shape but also the applicability of the AB-EMA for an unknown set of data., Graphical abstract Unlabelled Image

We demonstrate how terahertz time-domain spectroscopy (THz-TDS) can be used to quantify water absorption in hygrothermally aged simple and commercial epoxy systems supported by conventional gravimetric analysis.

Localized surface plasmons are highly confined modes at the subwavelength surfaces. The modes provide enhanced electric field intensity sites in close proximity to the surface which display potential applications in the form of optical-sensing devices. Intriguingly, at nanoscale, the modes can also increase the optical transmission through the aperture. In this work, we analyze the light transmission through a pyramid-shaped slit based on numerical simulations. We demonstrate the phenomenon by studying the behavior of Poynting vectors in the near surroundings of the slit. Furthermore, near and far transmitted optical intensities are calculated which show the supremacy of pyramid-shaped slit over the rectangular-shaped slit. The near and far field intensity through the pyramid slit is ∼2.25-times stronger than that of the rectangular slit. To see the influence of the shape of the slit on optical transmission, a reverse case, wherein pyramid-shaped slit is rotated by 180°, is also investigated. Based on our analysis, it is shown that enhancement of the output field emanates due to the excitation of the LSP modes while directionality of the field by a single slit depends on the shape of the slit. The study could be useful for the enhancement of fluorescent and Raman emissions from the molecules that are located eminently close to the slit.

In the field of non-destructive testing, terahertz sensing has been used to analyze a wide range of materials where the most successful applications have involved materials that are semi-transparent to terahertz radiation. In this work, we demonstrate the sensitivity of terahertz time-domain spectroscopy to quantify water absorption in hygrothermally aged simple and commercial epoxy systems supported by conventional gravimetric analysis.

In-line terahertz sensing has been demonstrated to measure the coating thickness of individual pharmaceutical tablets during coating operation. As coating uniformity is highly dependent on tablet mixing, this study presents our research progress to date on using in-line terahertz sensing to investigate the effects of baffle design, drum rotational speed and batch size, on tablet mixing inside a laboratory-sized perforated pan coater.

Metamaterial absorbers, due to their potential applications in the field of photonics, are vastly studied in the last decade. Herein, we present a novel design of a resonant metamaterial absorber in the terahertz (THz) region based on numerical simulations. This perfect THz absorber, due to its symmetry, is highly independent on the polarization state of an incident plane wave. Moreover, the absorber is insensitive to a wide range of incident angle from 0 to 70°. The absorbance approaches unity at a resonance frequency of 3.74 THz. The absorber shows remarkable results even at the two extreme incident angles, e.g. a minimum absorbance value of ∼80% was recorded at an incident angle of 70°. With this promising performance, the proposed THz absorber can serve as a possible sensing device for transparent analytes adsorbed on it. For this structure, aluminum and TiO2 are used. Both materials are commonly available for manufacturing photonic devices.

Terahertz (THz) spectra from the pure forms [i.e. the active pharmaceutical ingredients (APIs)] of four commonly used antimalarial drugs are reported. The well-defined spectral fingerprints obtained for these APIs in the spectral range of 0.1 THz–3 THz show the sensitivity of the THz time-domain spectroscopic (THz-TDS) method for screening antimalarial drugs. For identification purpose, two commercially available antimalarial tablets were detected. Clear spectral fingerprints of the APIs in the antimalarial tablets were obtained even amidst the several types of excipients present in the tablets. This observation further proves the high sensitivity of the THz techniques in tracking the presence or absence of API in a pharmaceutical tablet. We envisage that the spectral data obtained for these drugs can contribute to a spectroscopic database in the far infrared spectral region and hence support the modelling of THz sensing to differentiate between genuine and counterfeit antimalarial tablets.

Traditionally, the development of a new solid dosage form is formulation-driven and less focus is put on the design of a specific microstructure for the drug delivery system. However, the compaction process particularly impacts the microstructure, or more precisely, the pore architecture in a pharmaceutical tablet. Besides the formulation, the pore structure is a major contributor to the overall performance of oral solid dosage forms as it directly affects the liquid uptake rate, which is the very first step of the dissolution process. In future, additive manufacturing is a potential game changer to design the inner structures and realise a tailor-made pore structure. In pharmaceutical development the pore structure is most commonly only described by the total porosity of the tablet matrix. Yet it is of great importance to consider other parameters to fully resolve the interplay between microstructure and dosage form performance. Specifically, tortuosity, connectivity, as well as pore shape, size and orientation all impact the flow paths and play an important role in describing the fluid flow in a pharmaceutical tablet. This review presents the key properties of the pore structures in solid dosage forms and it discusses how to measure these properties. In particular, the principles, advantages and limitations of helium pycnometry, mercury porosimetry, terahertz time-domain spectroscopy, nuclear magnetic resonance and X-ray computed microtomography are discussed.

Heckel analysis is a widely used method for the characterisation of the compression behaviour of pharmaceutical samples during the preparation of solid dosage formulations. The present study introduces an optical version of the Heckel equation that is based on a combination of the conventional Heckel equation together with the linear relationship defined between the effective terahertz (THz) refractive index and the porosity of pharmaceutical tablets. The proposed optical Heckel equation allows us to, firstly, calculate the zero-porosity refractive index, and, secondly, predict the in-die development of the effective refractive index as a function of the compressive pressure during tablet compression. This was demonstrated for five batches of highly porous functionalised calcium carbonate (FCC) excipient compacts. The close match observed between the estimated in-die effective refractive index and the measured/out-of-die effective THz refractive index supports the validity of the proposed form of the equation. By comparing the measured and estimated in-die tablet properties, a clear change in the porosity and hence, the effective refractive index, due to post-compression elastic relaxation of the FCC compacts, has been observed. We have, therefore, proposed a THz-based compaction setup that will permit in-line monitoring of processes during tablet compression. We envisage that this new approach in tracking powder properties introduced in this preliminary study will lead to the onset of further extensive and detailed future studies.

Background: Liquid fuel adulteration has several far-reaching impacts such as environmental pollution. A widespread practice is typically the adulteration of diesel oil by kerosene. The relatively cheap price of kerosene is probably the most important reason for its usage in illegal adulteration. Herein, we demonstrate the use of a prototype optical sensor for efficient tracking of adulterated diesel oil. Methods: In this study, a prototype of an optical sensor for screening of fake diesel oil is proposed. The device exploits the phenomenon of laser light reflection from a fuel film over a roughened glass plate. The sensing mechanism of the devise is based on the refractive index mismatch between the glass and the fuel sample, and the wetting property of the fuel film over the roughened surface. For the sake of comparison, the refractive index for each of the fuel samples was measured at room temperature with the aid of an automatic temperature controlled Abbe table refractometer. The sensitivity of this prototype optical sensor was tested using training sets of diesel oil samples adulterated with low concentrations of kerosene. Results: Originally, a commercial handheld glossmeter, with a new innovation of a removable sensor head for liquid inspection is presented as a prototype sensor for the screening of possible adulteration of diesel oils with kerosene. The significant difference in the signal readings obtained from carefully prepared training sets of adulterated diesel oil composed of low percentages (5–15%) of kerosene has proven the high sensitivity of the developed sensor. Conclusions: The ability to detect low concentrations of kerosene in diesel using the newly developed hand-held prototype sensor proves its high sensitivity compared to a high-accuracy Abbe refractometer. We envisage that this proposed sensor could, in the future, be made accessible to the authorities as a mobile fake fuel measurement unit.

The rapid development of terahertz time-domain spectroscopy (THz-TDS) as a highly versatile analytical tool for the characterisation of pharmaceutical materials has drawn considerable attention over the past two decades. In this review an overview of the current advances in the use of THz-TDS for the characterisation of small organic molecular crystals and their solid-state modifications, the characterisation of amorphous drug products as well as biopharmaceutical solid state formulations are presented. In addition, due to its low absorption from typical pharmaceutical excipients and the low scattering losses given the relatively long wavelength, THz-TDS can be used for non-destructive porosity measurement and characterisation of the microstructure of tablet matrices. The method and its applications are introduced and explained in the context of complementary characterisation techniques.

Background The surface quality of pharmaceutical tablets plays an important role, especially in the drug release of a tablet and hence affects the bioavailability of the drug. Furthermore, important tablet’s properties such as coating uniformity and mechanical integrity that can be predicted based on the known surface properties manifest the inevitable link between a tablet’s surface property (e.g. Gloss, average surface roughness) and its efficacy. Methods In this article, laboratory based and handheld glossmeters as well as an optical profilometer were utilized for the detection of the surface properties of commercially available pharmaceutical tablets. Results As a case study, we measured the surface properties of authentic and counterfeit antimalarial tablets. Clear differences between authentic and fake tablets were detected based on the measured average surface roughness and gloss values of the tablet samples. Conclusions It is worth mentioning that this is the first time we have utilized both glossmeters for the purpose of surface quality investigation of real pharmaceutical tablets. It is therefore suggested that the handheld glossmeter is a useful device for quick inspection of tablet’s surface quality both in the production environments as well as for field screening of fake tablets., published version, peerReviewed

The objective of this study is to propose a novel optical compressibility parameter for porous pharmaceutical tablets. This parameter is defined with the aid of the effective refractive index of a tablet that is obtained from non-destructive and contactless terahertz (THz) time-delay transmission measurement. The optical compressibility parameter of two training sets of pharmaceutical tablets with a priori known porosity and mass fraction of a drug was investigated. Both pharmaceutical sets were compressed with one of the most commonly used excipients, namely microcrystalline cellulose (MCC) and drug Indomethacin. The optical compressibility clearly correlates with the skeletal bulk modulus determined by mercury porosimetry and the recently proposed terahertz lumped structural parameter calculated from terahertz measurements. This lumped structural parameter can be used to analyse the pattern of arrangement of excipient and drug particles in porous pharmaceutical tablets. Therefore, we propose that the optical compressibility can serve as a quality parameter of a pharmaceutical tablet corresponding with the skeletal bulk modulus of the porous tablet, which is related to structural arrangement of the powder particles in the tablet., final draft, peerReviewed

In this study, terahertz time domain spectroscopy (THz-TDS) is used to analyze how the geometry of a compact affects its pore structure (pore shape and orientation). By using flat-faced and biconvex compacts, it was evident from our analysis that pores tend to assume specific shapes and orientations based on the compact's geometry and this was found to significantly affect the extracted optical properties of samples prepared by mixing a material with polyethylene (PE) as diluent and subsequent compaction. However, such sensitivity to the pore properties opens a number of industrial applications such as for quality testing of pharmaceutical tablets. A comparison made between the PE based compacts and a set of pharmaceutical tablets prepared from the same formulation has revealed that flatfaced and biconvex compacts possess different pore geometries and hence different optical properties.

Terahertz pulsed imaging (TPI) coupled with a customised flow cell has previously been used successfully to study liquid transport in porous media, such as powder compacts. In some samples, the tracking of the liquid front remains challenging when the refractive indices of liquid and sample are similar and hence little contrast is observed. In this work, we found that even when the relative difference between the refractive indices of liquid and sample is high, it can still be challenging to track the reflection peak of water in some samples while it works fine in others. It is hypothesised that this is due to the formation of a water gradient in these samples due to their specific microstructure and we explore methods to overcome this limitation.

Biconvex pharmaceutical microcrystalline cellulose (MCC) compacts were investigated by the detection of terahertz (THz) pulse delay in the transmission measurement mode. The dimensions of the tablets were kept as constants but the porosity was a priori known variable. It is shown that the porosity of the biconvex compact has a linear correlation with the THz pulse delay. By constructing a calibration line between these two parameters (i.e. porosity and THz pulse delay), it is possible to non-invasively detect porosity of biconvex tablets. We suggest that this preliminary study could be the starting point of in-depth future studies on the screening of porosity and related properties of real biconvex pharmaceutical tablets using terahertz sensing techniques.

This work highlights the use of Hashin–Shtrikman (H–S) bounds in the prediction and verification of the effective refractive index, the height and the Young’s modulus of given training sets of pharmaceutical compacts using the measured time delay of a THz pulse traversing the compacts. Set A consisted of 13 microcrystalline cellulose (MCC) compacts whereas set B was made up of 5 starch acetate (SA) compacts. MCC is a typical ingredient of many pharmaceutical tablets. In the case of the MCC compacts, tight and closely matched bounds were obtained between the experimental, the calculated upper, lower bound values for the effective refractive index, and the height values. This promising outcome has shown the high possibility of utilizing H–S bounds in the verification and prediction of the decision level of useful parameters, which can serve as a quality check for pharmaceutical tablets. For the SA compacts, although less tight bounds were observed, the experimental values for the effective refractive index and the Young’s modulus were closely matched with the upper and the lower bounds, respectively. We therefore speculate based on the above observations that the MCC tablets contain an almost evenly distributed spherically shaped air voids whereas in the SA compacts, this assumption might not necessary be true.

Fast disintegrating tablets have commonly been used for fast oral drug delivery to patients with swallowing difficulties. The different characteristics of the pore structure of such formulations influence the liquid transport through the tablet and hence affect the disintegration time and the release of the drug in the body. In this work, terahertz time-domain spectroscopy and terahertz pulsed imaging were used as promising analytical techniques to quantitatively analyse the impact of the structural properties on the liquid uptake and swelling rates upon contact with the dissolution medium. Both the impact of porosity and formulation were investigated for theophylline and paracetamol based tablets. The drug substances were either formulated with functionalised calcium carbonate (FCC) with porosities of 45% and 60% or with microcrystalline cellulose (MCC) with porosities of 10% and 25%. The terahertz results reveal that the rate of liquid uptake is clearly influenced by the porosity of the tablets with a faster liquid transport observed for tablets with higher porosity, indicating that the samples exhibit structural similarity in respect to pore connectivity and pore size distribution characteristics in respect to permeability. The swelling of the FCC based tablets is fully controlled by the amount of disintegrant, whereas the liquid uptake is driven by the FCC material and the interparticle pores created during compaction. The MCC based formulations are more complex as the MCC significantly contributes to the overall tablet swelling. An increase in swelling with increasing porosity is observed in these tablets, which indicates that such formulations are performance-limited by their ability to take up liquid. Investigating the effect of the microstructure characteristics on the liquid transport and swelling kinetics is of great importance for reaching the next level of understanding of the drug delivery, and, depending on the surface nature of the pore carrier function, in turn controlling the performance of the drug mainly in respect to dissolution in the body.

Surface plasmon polaritons are electromagnetic surface waves, which, due to their nanoscale nature, are efficiently used for modifying an output of optical field through a metallic nanoslit, e.g., extraordinary optical transmission and beaming of light. Herein, the phenomenon of optical beaming by employing a regular array of semicylinder-shaped grooves around a nanoslit has been investigated based on numerical simulations. By analyzing the behavior of Poynting vectors in near surroundings of the slit, we have successfully demonstrated that grooves which are embedded on the layer at the exit side of the slit produce enhanced directionality of the output light than the unembedded ones. In case of semicylinder-shaped grooves, the calculated intensity of the output beam was 1.5-times, at near and far distances, higher than that of the grating grooves. Our analysis shows that positioning of the groove right at the exit of the slit is crucial for the enhancement of the beaming effect. This is due to the conversion of surface plasmon polaritons into a freely propagating field and the possible excitation of localized surface plasmons because of the presence of nanogroove. Furthermore, the proposed geometries are made of Aluminum, which is a plasmonic material and commonly applied for the fabrication of optical nanostructures. Manipulating of light (beaming, focusing/guiding, and splitting) by nanoslit can be beneficial to several applications such as nano-resolution optical imaging, sensors, and plasmonic circuits.

Pharmaceutical tablets are typically manufactured by the uni-axial compaction of powder that is confined radially by a rigid die. The directional nature of the compaction process yields not only anisotropic mechanical properties (e.g. tensile strength) but also directional properties of the pore structure in the porous compact. This study derives a new quantitative parameter, Sa, to describe the anisotropy in pore structure of pharmaceutical tablets based on terahertz time-domain spectroscopy measurements. The Sa parameter analysis was applied to three different data sets including tablets with only one excipient (functionalised calcium carbonate), samples with one excipient (microcrystalline cellulose) and one drug (indomethacin), and a complex formulation (granulated product comprising several excipients and one drug). The overall porosity, tablet thickness, initial particle size distribution as well as the granule density were all found to affect the significant structural anisotropies that were observed in all investigated tablets. The Sa parameter provides new insights into the microstructure of a tablet and its potential was particularly demonstrated for the analysis of formulations comprising several components. The results clearly indicate that material attributes, such as particle size and granule density, cause a change of the pore structure, which, therefore, directly impacts the liquid imbibition that is part of the disintegration process. We show, for the first time, how the granule density impacts the pore structure, which will also affect the performance of the tablet. It is thus of great importance to gain a better understanding of the relationship of the physical properties of material attributes (e.g. intragranular porosity, particle shape), the compaction process and the microstructure of the finished product.

In this paper, it is suggested that Young's modulus of pharmaceutical tablets with different porosity can be estimated from terahertz (THz) pulse time delay. We demonstrate such a possibility using a training set of tablets compressed from starch acetate. Once the mechanical properties are taught to the THz measurement system, using an ideal tablet as a reference, it is possible to get information about the Young's modulus of the tablet. Here, we show that there are optical counterparts of classical mechanical laws that couple the Young's modulus and porosity of the tablet.

By measuring the time delay of a terahertz pulse traversing a tablet, and hence its effective refractive index, it is possible to non-invasively and non-destructively detect the weight of tablets made of microcrystalline cellulose (MCC). Two sets of MCC tablets were used in the study: Set A (training set) consisted of 13 tablets with nominally constant height but varying porosities, whereas Set B (test set) comprised of 21 tablets with nominally constant porosity but different heights. A linear correlation between the estimated absolute weight based on the terahertz measurement and the measured weight of both sets of MCC tablets was found. In addition, it was possible to estimate the height of the tablets by utilizing the estimated absolute weight and calculating the relative change of height of each tablet with respect to an ideal tablet. A good agreement between the experimental and the calculated results was found highlighting the potential of this technique for in-line sensing of the weight, porosity and the relative change in height of the tablets compared to a reference/ideal tablet. In this context, we propose a quantitative quality control method to assess the deviations in porosity of tablets immediately after compaction.

This study demonstrates the analysis of anisotropic pore structures of highly porous pharmaceutical powder compacts by combining terahertz time-domain spectroscopy and in-situ measurements of the liquid penetration using terahertz pulsed imaging.

The physical properties and mechanical integrity of pharmaceutical tablets are of major importance when loading with active pharmaceutical ingredient(s) (API) in order to ensure ease of processing, control of dosage and stability during transportation and handling prior to patient consumption. The interaction between API and excipient, acting as functional extender and binder, however, is little understood in this context. The API indomethacin is combined in this study with microcrystalline cellulose (MCC) at increasing loading levels. Tablets from the defined API/MCC ratios are made under conditions of controlled porosity and tablet thickness, resulting from different compression conditions, and thus compaction levels. Mercury intrusion porosimetry is used to establish the accessible pore volume, pore size distribution and, adopting the observed region of elastic intrusion-extrusion at high pressure, an elastic bulk modulus of the skeletal material is recorded. Porosity values are compared to previously published values derived from terahertz (THz) refractive index data obtained from exactly the same tablet sample sets. It is shown that the elastic bulk modulus is dependent on API wt% loading under constant tablet preparation conditions delivering equal dimensions and porosity. The findings are considered of novel value in respect to establishing consistency of tablet production and optimisation of physical properties., final draft, peerReviewed

In order to find counterfeit drugs quickly and reliably, we have developed ‘tape method’ a transmission spectroscopic terahertz (THz) measurement technique and compared it with a standard attenuated total reflection (ATR) THz spectroscopic measurement. We used well-known training samples, which include commercial paracetamol and aspirin tablets to check the validity of these two measurement techniques. In this study, the spectral features of some active pharmaceutical ingredients (APIs), such as aspirin and paracetamol are characterized for identification purpose. This work covers a wide THz spectral range namely, 2-18 THz. This proposed simple but novel technique, the tape method, was used for characterizing API and identifying their presence in their dosage forms. By comparing the spectra of the APIs to their dosage forms (powder samples), all distinct fingerprints present in the APIs are also present in their respective dosage forms. The positions of the spectral features obtained with the ATR techniques were akin to that obtained from the tape method. The ATR and the tape method therefore, complement each other. The presence of distinct fingerprints in this spectral range has highlighted the possibility of developing fast THz sensors for the screening of pharmaceuticals. It is worth noting that, the ATR method is applicable to flat faced tablets whereas the tape method is suitable for powders in general (e.g. curved surface tablets that require milling before measurement). Finally, we have demonstrated that ATR techniques can be used to screen counterfeit antimalarial tablets.

In this paper, far-infrared (FIR) spectroscopic techniques have been employed to detect different calcium carbonate crystal concentrations in powder mixtures. We have compared absorption spectral features of both pure and mixtures of natural ground calcium carbonate (GCC) and synthetic precipitated calcium carbonate (PCC). It is evident that the absorbance data differentiate clearly and unequivocally between calcite and aragonite in the spectral range of 2–18 THz. Also, from the absorbance measurement of two sets of mixtures, we have revealed a linear relationship between the ratio of some selected absorbance peaks of the mixtures and concentration of a particular pigment within the mixture. This innovative technique could be a novel, practicable technique for quality control or for analyzing coating and/or filler pigments and extenders in the paper making and printing industries. Finally, we have proven in the case of paper that, surface roughness and print color play no role as far as the locations and magnitudes of the absorbance spectral features are concerned.

We report on the non-destructive quantification of the porosity of pharmaceutical compacts (microcrystalline cellulose tablets) by using both optical and terahertz techniques. For the full analysis of the porosity of pharmaceutical tablets, the results obtained in both cases have shown that optical and terahertz techniques are complementary. The intrinsic refractive index of microcrystalline cellulose was estimated using the effective refractive index obtained from the time delay of the THz pulse together with the Bruggeman model for effective media. Once this intrinsic refractive index is known, the unknown porosity of the tablet can be estimated with the aid of the measured effective refractive index as well as the thickness of the pharmaceutical tablet. The method was tested using a set of thirteen tablets having different porosities. It is shown that the error in the estimation of the unknown tablet’s porosity is less than 1%. In addition, surface roughness was measured by using an optical interferometer and gloss by using a diffractive-optical-element based glossmeter. The measurement was achieved by scanning the tablets with a probe beam and detecting the reflected light. The surface roughness and gloss data show relatively good correlation with the porosities of the tablets.

In this paper, the terahertz (THz) transmission measurement technique was applied to characterize titanium dioxide (TiO2) nanospheres and nanowires subjected to thermal treatments under various conditions. Differences in the spectral features of the nanospheres and nanowires were observed due to treatment and annealing of the samples in different gas atmospheres. The observations made can be explained based on the formation of new phonon bands and/or widening of the phonon bands due to polymorphism. A singly subtractive Kramers Kronig dispersion relation was utilized to estimate the frequency-dependent real refractive index of the various samples, having a priori unknown sample thickness, from the absorbance data.

In this study, terahertz time-domain spectroscopic (THz-TDS) technique has been used to ascertain the change in the optical properties, as a function of changing porosity and mass fraction of active pharmaceutical ingredient (API), of training sets of pharmaceutical tablets. Four training sets of pharmaceutical tablets were compressed with microcrystalline cellulose (MCC) excipient and indomethacin API by varying either the porosity, height, and API mass fraction or all three tablet parameters. It was observed, as far as we know, for the first time, that the THz time-domain and frequency-domain effective refractive index, as well as, the frequency-domain effective absorption coefficient both show linear correlations with the porosity and API mass fraction for training sets of real pharmaceutical tablets. We suggest that, the observed linear correlations can be useful in basic research and quality inspection of pharmaceutical tablets. Additionally, we propose a novel optical strain parameter, based on THz measurement, which yields information on the conventional strain parameter of a tablet as well as on the change of fill fraction of solid material during compression of porous pharmaceutical tablets. We suggest that the THz measurement and proposed method of data analysis, in addition to providing an efficient tool for basic research of porous media, can serve as one of the novel quality by design (QbD) implementation techniques to predict critical quality attributes (CQA) such as porosity, API mass fraction and strain of flat-faced pharmaceutical tablets before production.

A structure parameter that can be used to predict the pattern of arrangement of porous inclusions in pharmaceutical tablets is introduced. By utilizing the effective refractive index of a pharmaceutical tablet obtained from terahertz time-domain measurements, we have shown that there exists a promising correlation between the calculated structural parameter and the porosity of training sets of pharmaceutical tablets, having well-defined characterization. Knowing of the structural arrangement, i.e. combined constituent skeletal-pore elements in series, parallel or mixed within porous media, could serve as a basis for understanding the ingress and permeation of liquids in such media. In the realm of pharmaceutical applications, such knowledge of the structural arrangement of air voids within a medicinal tablet could enable correlation with mechanical strength and dissolution behaviour in aqueous systems.