Abstract-Determining the Effect of Photodegradation on Film Coated Nifedipine Tablets with Terahertz Based Coating Thickness Measurements

Noritaka Odani, Shikhar Mohan, Eiji Katod,  Hanzhou Feng, Yi Li. Md. Nayeem Hossain. James K.DrennenIII, Carl  A. Anderson,

https://www.sciencedirect.com/science/article/abs/pii/S0939641119305235

Film coating of nifedipine tablets is commonly performed to reduce photo-degradation. The coating thickness of these tablets is a primary dictating factor of photo-stability. Terahertz spectroscopy enables accurate measurement of coating thickness. This study identifies a method to determine an end-point of a photo-protective coating process by using coating thickness measurements from terahertz time of flight spectroscopy (THz-TOF). For this method, nifedipine tablets, at different coating thicknesses, were placed in a photostability chamber. The illumination conditions of the coated tablets were adjusted based on the time duration of these tablets inside the chamber. A multiple linear regression model was developed with the coating thickness estimates from THz-TOF and illumination conditions information to predict the amount of drug remaining after photo-degradation (percent label claim). The prediction error of this model was 1.03 % label claim in the range of 88.4 to 100.6 % label claim. According to this model, acceptable levels of photo-protection in illumination conditions of up to approximately 700,000 lux hours was achieved at the end of the coating process (approximately 50 µm coating thickness) performed in this study. These results suggest THz-TOF as a viable process analytical technology tool for process understanding and end-point determination of a photo-protective coating process.

Closing the terahertz gap: Tiny laser is an important step toward new sensors

A new imaging technology rapidly measures the chemical compositions of solids. A conventional image of a sample pill is shown at left; at right, looking at the same surface with terahertz frequencies reveals various ingredients as different colors. Such images would aid quality control and development in pharmaceutical manufacturing, as well as medical diagnosis and treatment.

https://www.eurekalert.org/multimedia/pub/207021.php

In a major step toward developing portable scanners that can rapidly measure molecules in pharmaceuticals or classify tissue in patients' skin, researchers have created an imaging system that uses lasers small and efficient enough to fit on a microchip.

The system emits and detects electromagnetic radiation at terahertz frequencies -- higher than radio waves but lower than the long-wave infrared light used for thermal imaging. Imaging using terahertz radiation has long been a goal for engineers, but the difficulty of creating practical systems that work in this frequency range has stymied most applications and resulted in what engineers call the "terahertz gap."

"Here, we have a revolutionary technology that doesn't have any moving parts and uses direct emission of terahertz radiation from semiconductor chips," said Gerard Wysocki, an associate professor of electrical engineering at Princeton University and one of the leaders of the research team.

Terahertz radiation can penetrate substances such as fabrics and plastics, is non-ionizing and therefore safe for medical use, and can be used to view materials difficult to image at other frequencies. The new system, described in a paper published in the June issue of the journal Optica, can quickly probe the identity and arrangement of molecules or expose structural damage to materials.

The device uses stable beams of radiation at precise frequencies. The setup is called a frequency comb because it contains multiple "teeth" that each emit a different, well-defined frequency of radiation. The radiation interacts with molecules in the sample material. A dual-comb structure allows the instrument to efficiently measure the reflected radiation. Unique patterns, or spectral signatures, in the reflected radiation allow researchers to identify the molecular makeup of the sample.

While current terahertz imaging technologies are expensive to produce and cumbersome to operate, the new system is based on a semiconductor design that costs less and can generate many images per second. This speed could make it useful for real-time quality control of pharmaceutical tablets on a production line and other fast-paced uses.

"Imagine that every 100 microseconds a tablet is passing by, and you can check if it has a consistent structure and there's enough of every ingredient you expect," said Wysocki.

As a proof of concept, the researchers created a tablet with three zones containing common inert ingredients in pharmaceuticals -- forms of glucose, lactose and histidine. The terahertz imaging system identified each ingredient and revealed the boundaries between them, as well as a few spots where one chemical had spilled over into a different zone. This type of "hot spot" represents a frequent problem in pharmaceutical production that occurs when the active ingredient is not properly mixed into a tablet.

The team also demonstrated the system's resolution by using it to image a U.S. quarter. Fine details like the eagle's wing feathers, as small as one-fifth of a millimeter wide, were clearly visible.

While the technology makes the industrial and medical use of terahertz imaging more feasible than before, it still requires cooling to a low temperature, a major hurdle for practical applications. Many researchers are now working on lasers that will potentially operate at room temperature. The Princeton team said its dual-comb hyperspectral imaging technique will work well with these new room-temperature laser sources, which could then open many more uses.

Because it is non-ionizing, terahertz radiation is safe for patients and could potentially be used as a diagnostic tool for skin cancer. In addition, the technology's ability to image metal could be applied to test airplane wings for damage after being struck by an object in flight.

In addition to Wysocki, the paper's Princeton authors are former visiting graduate student Lukasz Sterczewski (currently a postdoctoral scholar at NASA's Jet Propulsion Laboratory) and associate research scholar Jonas Westberg. Other co-authors are Yang Yang, David Burghoff and Qing Hu of the Massachusetts Institute of Technology; and John Reno of Sandia National Laboratories. Support for the research was provided in part by the Defense Advanced Research Projects Agency and the U.S. Department of Energy.

Abstract-Desolvation behavior of indinavir sulfate ethanol and follow-up by terahertz spectroscopy

Masataka Ito, Reiko Tokuda, Hironori Suzuki, Tomoaki Sakamoto, Katsuhide Terada, Shuji Noguch

https://www.sciencedirect.com/science/article/pii/S0378517319304806

Active pharmaceutical ingredients are composed of single-component or multicomponent crystals. Multicomponent crystals include salts, co-crystals, and solvates. Indinavir sulfate is the ethanol solvate form of indinavir that is known to deliquesce through moisture absorption. However, the detailed behavior of solvent molecules in the crystal has not been investigated. In this study, we studied the desolvation mechanism of indinavir sulfate ethanol and investigated the behavior of solvent molecules in the solid from. Indinavir sulfate ethanol contained 1.7 molecules of ethanol, 0.7 of which desolvated at room temperature. They were originally two ethanol solvent molecules; one molecule of ethanol desolvated at room temperature, and the conformation of the remaining ethanol and t-butyl groups changed in conjunction with the removal of one ethanol molecule. Desolvation could hardly be detected by powder X-ray diffraction; however, it was detected using terahertz spectroscopy. Terahertz measurement of desolvation showed a high correlation with thermogravimetry data, suggesting that desolvation could be observed non-destructively using terahertz spectroscopy. We concluded that indinavir sulfate 1 ethanol deliquesced at 60% relative humidity, and it turned into an amorphous solid after drying.

Abstract-Temperature- and pH-dependent protein conformational changes investigated by terahertz dielectric spectroscopy

Ziyi Zang, Shihan Yan, Xiaohui Han, Dongshan Wei. Hong-Liang Cui, Chunlei Du,




https://www.sciencedirect.com/science/article/pii/S1350449518305267

Polypeptides and protein drugs have received enormous attention from pharmaceutical industry, medical sector and consumer groups because of a favourable combination of their bioactivity, specificity and overall success rate for the treatment of a variety of diseases. The efficacy and safety of drugs may be degraded due to fluctuating environmental factors, accompanied by changes of the natural conformation of protein. Thus, it is necessary and meaningful to evaluate drug status before use. To that end, the evolving new and pre-existing protein activity/conformation technologies have proven to ensure the safety of drug use consistently. Recently, terahertz time-domain spectroscopy (THz-TDS) has demonstrated suitability for label-free and non-destructive detection of polypeptide and protein conformational changes. In this paper, THz optical parameters of pepsin solutions under different temperatures and with varying pH are measured to demonstrate the feasibility and the considerable potential of THz spectroscopic method in detecting protein drugs. In cases where temperature or pH change is apparent, the THz absorption coefficient, the refractive index, and the dielectric loss tangent change noticeably, independently verified by enzyme activity testing. These findings strongly support the conclusion that THz spectroscopy of pepsin solutions can be used for qualitative analysis to identify the folding or unfolding of protein drugs caused by changes of environmental factors, laying the foundation of a new label-free method for quality control of protein drugs.

Abstract-A quantitative comparison of in-line coating thickness distributions obtained from a pharmaceutical tablet mixing process using discrete element method and terahertz pulsed imaging

Chunlei Pei, Hungyen Lin, Daniel Markl, Yao-ChunShen, J.Axel Zeitler, James A.Elliott,

https://www.sciencedirect.com/science/article/pii/S0009250918304172

The application of terahertz pulsed imaging (TPI) in the in-line configuration to monitor the coating thickness distribution of pharmaceutical tablets has the potential to improve the performance and quality of the spray coating process. In this study, an in-line TPI method is used to measure coating thickness distributions on pre-coated tablets during mixing in a rotating pan, and compared with results obtained numerically using the discrete element method (DEM) combined with a ray-tracing technique. The hit rates (i.e. the number of successful coating thickness measurements per minute) obtained from both terahertz in-line experiments and the DEM/ray-tracing simulations are in good agreement, and both increase with the number of baffles in the mixing pan. We demonstrate that the coating thickness variability as determined from the ray-traced data and the terahertz in-line measurements represents mainly the intra-tablet variability due to relatively uniform mean coating thickness across tablets. The mean coating thickness of the ray-traced data from the numerical simulations agrees well with the mean coating thickness as determined by the off-line TPI measurements. The mean coating thickness of in-line TPI measurements is slightly higher than that of off-line measurements. This discrepancy can be corrected based on the cap-to-band surface area ratio of the tablet and the cap-to-band sampling ratio obtained from ray-tracing simulations: the corrected mean coating thickness of the in-line TPI measurements shows a better agreement with that of off-line measurements.

Abstract-Optical Properties of Meloxicam in the Far-Infrared Spectral Region

Yusuf Samet Aytekin, Mustafa Köktürk, Adam Zaczek, Timothy M. Korter, Edwin J. Heilweil, Okan Esenturk,

https://www.sciencedirect.com/science/article/pii/S0301010418302337

One of the most commonly used nonsteroidal anti-inflammatory active pharmaceutical ingredient called Meloxicam has been characterized spectroscopically both by Terahertz (THz) time domain spectroscopy (THz-TDS) and by Fourier Transform Infrared (FTIR) spectroscopy in far-IR regions of electromagnetic spectrum; 0.2 THz to 20 THz. While many relatively sharp features are observed in the far-IR range between 2 THz to 20 THz as expected for being an organic substance, very distinct and relatively strong absorption bands are also observed at 1.00, 1.66, 2.07 and 2.57 THz in the THz range. These well separated, defined, and fairly strong spectral features can be used for discrimination and quantification of Meloxicam in drug analysis. Frequency dependent refractive index of the drug was determined in a range of 0.2 THz and 2.7 THz, where an almost constant index was observed with an average index of 1.75. Powder XRD, and solid-state Density Functional Theory (SS-DFT) calculations were utilized to determine the crystalline form of the Meloxicam sample in its enolic crystalline form. Single molecule DFT calculations were also performed in all four possible structures of Meloxicam. In addition, the capability of THz waves transmission through common packaging materials is demonstrated for possibility of future on-site analysis. The results suggest that drug analysis will be possible to perform not only at every stage of manufacturing without destruction but also directly at the shelf of a market after development of portable THz technologies.

Abstract-UV Absorption Spectroscopy in Water-Filled Antiresonant Hollow Core Fibers for Pharmaceutical Detection

Jonas Hamperl,  Jens Kobelke, Karina Weber, Thomas Henkel, Markus A. Schmidt,

http://www.mdpi.com/1424-8220/18/2/478

Due to a worldwide increased use of pharmaceuticals and, in particular, antibiotics, a growing number of these substance residues now contaminate natural water resources and drinking supplies. This triggers a considerable demand for low-cost, high-sensitivity methods for monitoring water quality. Since many biological substances exhibit strong and characteristic absorption features at wavelengths shorter than 300 nm, UV spectroscopy presents a suitable approach for the quantitative identification of such water-contaminating species. However, current UV spectroscopic devices often show limited light-matter interaction lengths, demand sophisticated and bulky experimental infrastructure which is not compatible with microfluidics, and leave large fractions of the sample analyte unused. Here, we introduce the concept of UV spectroscopy in liquid-filled anti-resonant hollow core fibers, with large core diameters and lengths of approximately 1 m, as a means to overcome such limitations. This extended light-matter interaction length principally improves the concentration detection limit by two orders of magnitude while using almost the entire sample volume—that is three orders of magnitude smaller compared to cuvette based approaches. By integrating the fibers into an optofluidic chip environment and operating within the lowest experimentally feasible transmission band, concentrations of the application-relevant pharmaceutical substances, sulfamethoxazole (SMX) and sodium salicylate (SS), were detectable down to 0.1 µM (26 ppb) and 0.4 µM (64 ppb), respectively, with the potential to reach significantly lower detection limits for further device integration.

Abstract-Analysis of Active Pharmaceutical Ingredients by Terahertz Spectroscopy

Y. Samet Aytekin, Mustafa Köktürk, Okan Esenturk

https://link.springer.com/chapter/10.1007/978-94-024-1093-8_10

Spectra of solid state active pharmaceutical ingredients obtained by Terahertz (THz) Time Domain Spectrometer in terahertz region of electromagnetic spectrum are presented. Each sample showed unique spectral features in 10.0–90.0 cm−1 indicating the potential use of THz spectroscopy for identification and quantification of drugs. Spectroscopic information of drugs would be needed in near future when THz technology further develops for on-site analysis and characterisation.

Abstract-Terahertz Spectroscopy Applications in Medicament Analysis

• Kateřina Sulovská

https://link.springer.com/chapter/10.1007/978-3-319-53934-8_6

Terahertz spectroscopy came to the attention of the broader scientific community in the 90s of the 20th century with the development of science and technology in particular, enabling to work in terahertz spectral region. Terahertz spectroscopy has a wide possibilities of applications beginning in classical spectroscopy of gun powders, plastics, explosives, liquids, through terahertz imaging of medicaments, tissues, materials or layers, to remote observation/identification of hidden objects mainly for security purposes. The aim of this paper is to introduce possible applications in analysis of pharmaceuticals with different amount of active ingredient content. According to the results, the classical terahertz spectroscopy is not as suitable as other spectroscopic methods targeted on analyzing content of pharmaceuticals showing persistent inconveniences of this spectroscopy. All measurements were done using the TPS Spectra 3000 instrument.

Using Terahertz Spectroscopy to Penetrate Non-Conducting Materials

http://www.azom.com/article.aspx?ArticleID=13913

Introduction

Many recent studies have given focus to amorphous active pharmaceutical ingredients (APIs). In most cases, the amorphous form facilitates greater bioavailability of the API. Studies have been conducted to gain further knowledge on the transitions and stabilities of amorphous APIs. The dynamics of amorphous APIs have been traditionally investigated using methods such as inelastic neutron scattering and dielectric spectroscopy. However, these techniques are not only expensive, but also time intensive.

Terahertz Spectroscopy

Terahertz spectroscopy technique is non-destructive as well as non-ionizing, and is capable of penetrating non-conducting materials. It is a useful technique in many fields, including medical imaging, art preservation and pharmaceuticals.

In the studies of amorphous materials, the stabilities of amorphous APIs can be predicted using terahertz spectroscopy. Also, the underlying physical properties governing the stabilities of amorphous APIs can be further explored using this technique.

TeraView TeraPulse 4000 Terahertz Spectrometer

The TeraPulse 4000 terahertz spectrometer is a portable instrument that can perform both transmission and reflection measurements within a single box. The unit can be used along with all of TeraView's existing imaging and spectroscopy modules and accessories.

The TeraPulse 4000 is TeraView's new spectrometer and imaging bench-top unit with a modular design, thus allowing all accessories to be fully used for reflection and transmission measurements. Equipped with TeraView's proprietary semiconductor based technology, the TeraPulse offers market leading signal to noise, with a quality signal up to 4 THz. The option of extending this beyond 7 THz also exists.

Related Stories

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• TeraCota - Terahertz Coating Thickness Analysis

The TeraPulse’s modular design not only simplifies any maintenance, but also allows it to automatically accept/recognize the company’s extensive and unique range of accessories. Smooth operation of the unit is ensured by the newly developed software. Options are also available for the instrument to be integrated into a suitable industrial casing, making it to be compliant with IP65 and IP67 standards.

Experiment

Terahertz spectroscopy has traditionally been used to investigate crystalline materials due to the possibility of acquiring a unique spectrum for the molecular solid being studied. During the analysis of amorphous materials, the terahertz spectra are often observed like a rising, featureless absorption. More recently, this technique has been employed to investigate the dynamics, stability and how these two properties are linked in these amorphous APIs.

The rapid cooling of a liquid to a solid leads to the formation of amorphous APIs. During this process, fast-cooling dynamics allow for the system to avoid crystallization and become trapped in a disordered state, a glass. The temperature where this transition occurs is called the glass transition temperature, Tg. The temperatures higher and lower than Tg show differing rates for the changes in the dynamics. These relaxation dynamics are classified into two categories: lower-frequency alpha and higher frequency beta relaxation processes. The alpha relaxations represent intermolecular motions and the beta relaxations represent intramolecular motions. Temperature plays a key role in these relaxations and each of them has a glass transition temperature associated with it.

Results and Discussion

In a recent work, it has been demonstrated that terahertz spectroscopy can detect the glass transition temperatures and the rate at which the relaxation frequency modulates as a function of temperature. Moreover, a direct relationship has been established between the secondary Johari-Goldstein ß relaxation and the stability of amorphous APIs. In addition, data obtained from terahertz spectroscopy can reveal the dielectric loss in these materials which can be applied to determine the stabilities of amorphous materials.

Abstract-Non-destructive Prediction of Enteric Coating Layer Thickness and Drug Dissolution Rate by Near-infrared spectroscopy and X-ray computed tomography

Aoi Ariyasu, 

Yusuke Hattori, 

Makoto Otsuka

http://www.sciencedirect.com/science/article/pii/S0378517317302983

The coating layer thickness of enteric-coated tablets is a key factor that determines the drug dissolution rate from the tablet. Near-infrared spectroscopy (NIRS) enables non-destructive and quick measurement of the coating layer thickness, and thus allows the investigation of the relation between enteric coating layer thickness and drug dissolution rate. Two marketed products of aspirin enteric-coated tablets were used in this study, and the correlation between the predicted coating layer thickness and the obtained drug dissolution rate was investigated. Our results showed correlation for one product; the drug dissolution rate decreased with the increase in enteric coating layer thickness, whereas, there was no correlation for the other product. Additional examination of the distribution of coating layer thickness by X-ray computed tomography (CT) showed homogenous distribution of coating layer thickness for the former product, whereas the latter product exhibited heterogeneous distribution within the tablet, as well as inconsistent trend in the distribution between the tablets. It was suggested that this heterogeneity and inconsistent trend in layer thickness distribution contributed to the absence of correlation between the layer thickness of the face and side regions of the tablets, which resulted in the loss of correlation between the coating layer thickness and drug dissolution rate. Therefore, the predictability of drug dissolution rate from enteric-coated tablets depended on the homogeneity of the coating layer thickness. In addition, the importance of micro analysis, X-ray CT in this study, was suggested even if the macro analysis, NIR spectroscopy (NIRS) in this study, are finally applied for the measurement.

Abstract-Optics-based compressibility parameter for pharmaceutical tablets obtained with the aid of the terahertz refractive index

Mousumi Chakraborty,  Cathy Ridgway, Prince Bawuah, Daniel Markl, Patrick A.C. Gane, Jarkko Ketolainen, J.Axel Zeitler, Kai-Erik Peiponen,

http://www.sciencedirect.com/science/article/pii/S037851731730279X

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.

Abstract-Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements

Daniel Markl, Johanna Sauerwein, Daniel J. Goodwin, Sander van den Ban, J. Axel Zeitler

http://link.springer.com/article/10.1007/s11095-017-2108-4

The aim of this study was to establish the suitability of terahertz (THz) transmission measurements to accurately measure and predict the critical quality attributes of disintegration time and the amount of active pharmaceutical ingredient (API) dissolved after 15, 20 and 25 min for commercial tablets processed at production scale.

Use of Terahertz imaging in the pharmaceutical industry talk at this year’s Photonics West by TeraView

http://www.news-medical.net/news/20170130/Use-of-Terahertz-imaging-in-the-pharmaceutical-industry-talk-at-this-yeare28099s-Photonics-West-by-TeraView.aspx

TeraView, the pioneer and leader in terahertz technology and solutions is pleased to announce that Dr Phil Taday, Head of Applications at TeraView, will be giving an invited talk on the use of Terahertz imaging in the pharmaceutical industry at this year’s Photonics West event to be held at The Moscone Center, San Francisco, USA.

TeraView’s Dr Philip Taday will be presenting an invited paper at the event entitled ‘Using terahertz-pulsed imaging (TPI) to study osmotic tablets’. The paper is the result of TeraView’s long term relationship with the pharmaceutical industry, and highlights TeraView’s commitment in providing solutions to the industry.

“We are excited to invite TeraView to present at this year’s meeting. It is great to see terahertz technology solving real-world problems for the pharmaceutical industry and we look forward to hearing the talk” said Dr. Frank Ellrich, Group Manager Optical Terahertz Measurement Techniques, Fraunhofer Institute for Industrial Mathematics ITWM. Dr Ellrich is organizing a session at this year’s conference on “Thickness Measurements using Terahertz Technologies”

TeraView’s Dr Philip Taday commented “The paper is the result of a long term collaboration between TeraView and a major pharmaceutical customer. I am very excited by the continuing integration of TeraView within the pharmaceutical industry and the successful application of terahertz technology in this field”. Dr Taday is the author on over a hundred peer-viewed papers, with over fifty in the area of the application of terahertz technology.

We are very proud of TeraView’s achievements in working closely with the pharmaceutical industry, this further marks our position as a leader in providing technology to a diverse customer base. Notably, it highlights our ability to put into work solutions for our customers, and to support their current and future requirements.”

Professor Sir Michael Pepper, TeraView’s Chief Scientific Director

TeraView continues to offer the pharmaceutical industry both analytical instrumentation and also a fee-for-service facility. The later allowing the industry to access TeraView’s extensive applications knowledge, intellectual property and know-how.

About Terahertz

Terahertz light lies between infra red and microwaves, and as such has unique properties which enables it to pass through objects and to transmit images and compositional (spectroscopic) information that is ordinarily hidden. Terahertz is non destructive, safe and fast, making it the ideal inspection and imaging modality for many applications across a range of industries.

TeraView has demonstrated the potential of terahertz technology in a number of applications including the detection of hidden weapons and explosives in security screening, monitoring the quality of pharmaceutical drugs, high value coatings used in automotive and other industries, as well as medical imaging of cancer.

About TeraView

TeraView is the world’s first and leading company solely focused upon the application of terahertz light to provide solutions to customer issues. A spin out from the Toshiba Corporation and Cambridge University, TeraView has developed its proprietary technology across a number of markets. These include fault analysis and quality assurance for semiconductor chips used in mobile computing and communications, as well as non destructive inspection of high value coatings used in the automotive, pharmaceutical, food and solar industries.

With the largest number of systems in the field, as well as applications know-how made available to customers via a team of dedicated scientists using intellectual property and knowledge in peer-reviewed scientific publications, TeraView is uniquely placed to deliver the business benefits of terahertz to customers. Headquartered in Cambridge UK, sales and customer support are available throughout the Far East, North America and Europe either directly or through a network of distributors.

Non-invasive screening method reveals important properties of pharmaceutical tablets

Information on significant properties of pharmaceutical tablets, such as their mechanical strength and dissolution, can now be obtained without resorting to the conventional, time-consuming and destructive testing methods, according to a new study completed at the University of Eastern Finland. A new structural descriptive parameter based on terahertz (THz) time-domain techniques allow for a non-invasive detection of pharmaceutical tablet parameters, constituting a research breakthrough in the field of pharmacy

https://www.sciencedaily.com/releases/2017/01/170110091904.htm

The study focused on non-contact quality inspection of pharmaceutical tablets using terahertz time-domain techniques. Terahertz radiation represents the far end of the infrared band and it has unique properties that permit a quick and safe identification of pharmaceutical tablet properties. Using THz radiation, which is invisible and safe for human beings, it is possible to determine what a tablet is made of, including the nature of its constituents and how they are arranged. To this effect, the study has developed a novel structural descriptive parameter for pharmaceutical tablets, addressing the orientation of their microscopic structure. The parameter provides information on the pattern of arrangement of the various particulates as well as air pores within a tablet.

This fast and non-destructive screening method has significant applications in the inspection of the quality of individual tablets during production, providing information on the amount of active pharmaceutical ingredient, tablet porosity and weight, among other things. Another important application is that this method can detect counterfeit and substandard tablets (for example fake antimalarial tablets) flooding the markets in developing countries, where counterfeit drugs are a major cause of mortality.

The parameter constitutes a research breakthrough in the field of pharmacy, as in-depth understanding of its behaviour gives information on, e.g., the mechanical strength, content uniformity and dissolution of pharmaceutical tablets.

By utilising training sets of pharmaceutical tablets, scientists at the University of Eastern Finland in collaboration with scientists at the University of Cambridge, UK, and in Switzerland have successfully demonstrated the ability to non-invasively detect the porosity, weight and height of tablets.. Based on these promising results, the researchers believe that an alternative non-destructive approach for quality screening of tablets can, in the future, replace the conventional destructive techniques such as mercury intrusion porosimetry. Hence, pharmacists and pharmaceutical scientists can now screen individual tablets even in the production line.

Since the majority (about 80%) of administered drugs are tablets, there is a significant need for a process analytical technology (PAT) tool that will permit the screening of individual pharmaceutical tablets before they reach end users. The methods were presented by Prince Bawuah, MSc, in his doctoral dissertation, and the findings were originally published in the International Journal of Pharmaceutics, European Journal of Pharmaceutics and Biopharmaceutics and Optical Review. The findings serve not only the pharmaceutical industry, but also pharmaceutical research.

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Story Source:

Materials provided by University of Eastern Finland. Note: Content may be edited for style and length.

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Journal Reference:

1. Prince Bawuah, Mousumi Chakraborty, Tuomas Ervasti, J.Axel Zeitler, Jarkko Ketolainen, Patrick A.C. Gane, Kai-Erik Peiponen. A structure parameter for porous pharmaceutical tablets obtained with the aid of Wiener bounds for effective permittivity and terahertz time-delay measurement. International Journal of Pharmaceutics, 2016; 506 (1-2): 87 DOI: 10.1016/j.ijpharm.2016.04.026

Using Ondax THz-Raman Systems for Quick and Accurate Identification of Polymorphs in Pharmaceuticals

http://www.azooptics.com/Article.aspx?ArticleID=1146

Introduction

Due to the different forms or molecular structures of a compound that influence the stability, efficacy or bio-availability of the drug, polymorphism is observed in most active pharmaceutical ingredients (APIs). These structural changes can take place during formulation, packaging, storage, and handling.

Pharmaceutical manufacturers need to identify polymorphs reliably and rapidly during all stages of production, from development to manufacturing and quality control. In this article, the advantages of Ondax THz-Raman® systems over conventional methods to identify polymorphs in pharmaceuticals are discussed.

Rapid and reliable identification of polymorphs is critical in pharmaceutical manufacturing

Existing Techniques

The structural shifts of a compound can be determined in several ways, including X-ray diffraction (XRD), Terahertz (THz) spectroscopy, and Raman spectroscopy. Raman spectroscopy is used to monitor small band shifts in the “fingerprint” region (200 - 1800 cm-1), but this reveal subtle shifts in functional groups, and are generally hard to detect during phase or polymorphic changes.

XRD techniques can produce conclusive and quantitative analysis, but they require costly equipment and destructive off-line testing to accomplish this. THz spectroscopy can easily differentiate structural shifts, but it has a limited spectroscopic range, is moisture-sensitive, costly, and requires special sample preparation.

Ondax Systems

With Ondax THz-Raman® systems, the range of traditional Raman spectroscopy can be extended to the terahertz/low frequency regime, where inter- and intra-molecular structures can be clearly differentiated, as shown in Figure 1.

THz-Raman spectra are capable of differentiating synthetic pathways, raw materials, and contaminants. It can also be used for surety testing and counterfeit detection. Anti-Stokes signals also improve SNR, and add to Raman intensity.

Ondax THz-Raman® systems offer quick, unambiguous differentiation of polymorphs, and preserve the complete Raman “fingerprint region” for chemical identification.

Figure 1. THz-Raman spectra for polymorphs of various APIs showing clear differentiable peaks.

Key Features

The following are the key features and advantages of Ondax systems:

• Simultaneous chemical and structural analysis
• Helpful for counterfeit detection or surety testing
• Fast, reliable polymorph identification, including conformers, isomers, hydrates, and co-crystals
• Compatible with traditional Raman spectrometers
• Available in benchtop or microscope configurations at 532, 633, 785, and 830 nm
• Non-destructive, and no sample preparation required
• Simple, compact, and cost-effective

Single System Handles THz-Raman and Fingerprint Region Measurements

Due to environmental conditions and formulation/processing methods, many compounds go through structural changes. Figure 2 shows the spectra that displays two polymorphs of carbamazepine (Form 2 and Form 3).

Compared to the conventional fingerprint region (gold background), the THz-Raman range (green background) show distinct differentiating signals, improving the ease and reliability of polymorph identification.

Figure 2. Two polymorphs of carbamazepine (Form 2 and Form 3)

The patented THz-Raman® Spectroscopy Systems from Ondax​ extend the range of conventional Raman spectroscopy into the THz/low frequency regime. The systems explore the same range of energy transitions as THz spectroscopy, without limiting the ability to measure the fingerprint region. This enables simultaneous analysis of chemical composition and molecular structure for advanced materials characterization.

All of the THz-Raman® systems are compact, robust, plug-and-play platforms. These easy-to-use systems offer throughput and speed at an affordable price. THz-Raman® solutions can be used for any application, due to their broad range of sample interfaces, wide selection of excitation wavelengths from 488 to 1064 nm, and optional polarization control.

Figure 3. THz-Raman® systems showing benchtop, probe and microscope configurations.

This information has been sourced, reviewed and adapted from materials provided by Ondax.

For more information on this source, please visit Ondax.

Teraview Blog- Abstract-Pharmaceutical applications of terahertz spectroscopy and imaging

Daniel Markl ; Michael T. Ruggiero and J. Axel Zeitler

http://terahertzspectroscopyandimaging.blogspot.com/2016/08/pharmaceutical-applications-of.html?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+TerahertzSpectroscopyAndImaging+%28terahertz+spectroscopy+and+imaging%29

Terahertz spectroscopy and imaging techniques have advanced the chemical and physical characterisation of active pharmaceutical ingredients (APIs), excipients and final solid dosage forms. Terahertz radiation can be used to investigate both chemical and solid structures, as well as provide information on the bulk morphology of pharmaceutical materials. The penetrating and non-destructive properties of terahertz light, coupled with its high acquisition rate, makes this technology a promising candidate for process analytical technology (PAT) applications.

Terahertz radiation corresponds to frequencies between the microwave and infrared regions of the electromagnetic spectrum (300 GHz to 10 THz, or wavelengths of 1mm to 1μm). For many years the terahertz region had been referred to as the ‘terahertz gap’ because of the difficulties in generating and detecting terahertz light. This has changed over the past few decades due to major advances that have brought down costs and instrument size, from $500,000+ laser systems that can take up an entire laboratory space to sub-$100,000 benchtop – and even hand-held – devices. Such breakthroughs have brought terahertz techniques into the mainstream and have enabled terahertz technologies to be implemented in industrial settings.

Collaboration furthers understanding of the stability of drug materials

http://www.cambridgenetwork.co.uk/news/understanding-the-stability-of-drug-materials/


TeraView, the pioneer and leader in terahertz technology and solutions, is pleased to announce that as part of its ongoing collaboration with the University of Cambridge, it has exclusively licensed a new University patent application pertaining to the formulation of drug ingredients using amorphous materials.
This latest patent complements TeraView’s own portfolio of 10 granted patents in the pharmaceutical field which encompass intellectual property addressing tablets and drug formulation. This patent will assist TeraView's collaborations with leading pharmaceutical companies, which is helping to improve the speed of drug formulation, as well as the lifetime of drug products and their efficiency of manufacture.

The inventors of the new patent are Dr Axel Zeitler and Dr Juraj Sibik, from the Department of Chemical Engineering and Biotechnology at the University of Cambridge. Their invention is a new method of using terahertz spectroscopy to investigate the stability of amorphous materials, which can be used as active ingredients in drugs in the pharmaceutical industry. Amorphous ingredients have the potential to increase bioavailability (absorption by the body) of poorly soluble drugs when administered orally in the form of tablets or capsules.

Commenting on the collaboration with TeraView, Dr Zeitler stated ‘Our work on amorphous materials has proven to be of interest to the scientific community, in both its applications to materials science as well as the terahertz spectroscopy. We have also had substantial interest from pharmaceutical companies. Our long-standing relationship with TeraView, and its position as the leading provider of terahertz solutions, makes TeraView a natural partner to make our invention available to the wider industrial community.’

The agreement strengthens TeraView’s position as the global leader in terahertz technology. It complements TeraView’s existing portfolio of internationally granted patents in the application of terahertz technology to the pharmaceutical sciences and industry. TeraView’s intellectual property includes the use of terahertz to aid in the development of new drug formulations and solid dosage forms, as well as quality assurance in production. TeraView patents address issues such as delamination in solid dosage forms, dissolution properties of tablets, tablet coating integrity which is important for many controlled release products, as well as the use of terahertz spectroscopy to detect and quantify different crystalline forms of drugs (polymorphism).

 Dr Phil Taday, a Principal Scientist and Head of Applications at TeraView, said of the agreement ‘Understanding the stability of amorphous materials is clearly of increasing importance to the pharmaceutical industry.  TeraView sees this patent as an important addition to our portfolio, with interest shown already by major pharmaceutical companies.’

 Dr Don Arnone, Chief Executive Officer of TeraView, commented: ’This agreement further solidifies our relationship with Dr Zeitler’s group, and we are proud to be associated with his work and that of his team. This collaboration, where we have provided TeraView systems and other means of support, is a very good example of the sort of collaboration we seek to establish with world experts in their fields, such as Dr Zeitler.’

About Terahertz

Terahertz light lies between infra red and microwaves, and as such has unique properties which enables it to pass through objects and to transmit images and compositional (spectroscopic) information that is ordinarily hidden. Terahertz is non destructive, safe and fast, making it the ideal inspection and imaging modality for many applications across a range of industries.

TeraView has demonstrated the potential of terahertz technology in a number of applications including the detection of hidden weapons and explosives in security screening, monitoring the quality of pharmaceutical drugs, high value coatings used in automotive and other industries, as well as medical imaging of cancer.  In the semiconductor industry, Electro Optical Terahertz Pulse Reflectometry (EOTPR) is the world’s first use of terahertz to isolate the location of faults and manufacturing quality variations in integrated circuit packaging.  EOTPR has been widely accepted by the leading semiconductor manufacturers as their tool of choice for isolating defects in advanced integrated circuit packages.

About the Terahertz Applications Group

The Terahertz Applications Group is part of the Department of Chemical Engineering and Biotechnology at the University of Cambridge (http://thz.ceb.cam.ac.uk). By using terahertz spectroscopy and imaging, the group is aiming to understand the physical characteristics of a wide variety of materials spanning the fields of pharmaceuticals, catalysis, biologicals, nanotechnology and non-destructive testing.

About TeraView

TeraView (www.teraview.com ) is the world’s first and leading company solely focused upon the application of terahertz light to provide solutions to customer issues. A spin out from the Toshiba Corporation and Cambridge University, TeraView has developed its proprietary technology across a number of markets. These include fault analysis and quality assurance for semiconductor chips used in mobile computing and communications, as well as non destructive inspection of high value coatings used in the automotive, pharmaceutical, food and solar industries. With the largest number of systems in the field, as well as applications know-how made available to customers via a team of dedicated scientists using intellectual property and knowledge in peer-reviewed scientific publications, TeraView is uniquely placed to deliver the business benefits of terahertz to customers. Headquartered in Cambridge UK, sales and customer support are available throughout the Far East, North America and Europe either directly or through a network of distributors.