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.

Abstract-Measuring the Elasticity of Poly-l-Proline Helices with Terahertz Spectroscopy

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http://onlinelibrary.wiley.com/doi/10.1002/anie.201603825/abstract

An approach combining terahertz spectroscopy, X-ray diffraction, and solid-state density functional theory was utilized to accurately measure the elasticities of poly-l-proline helices by probing their spring-like vibrational motions. In their communication (DOI:10.1002/anie.201602268), T. M. Korter and co-workers reveal that poly-l-proline is less rigid than commonly expected, and that the all-cis and all-trans helical forms exhibit significantly different Young's moduli.

Abstract-Measuring the Elasticity of Poly-l-Proline Helices with Terahertz Spectroscopy

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http://onlinelibrary.wiley.com/doi/10.1002/ange.201602268/abstract


The rigidity of poly-l-proline is an important contributor to the stability of many protein secondary structures, where it has been shown to strongly influence bulk flexibility. The experimental Young's moduli of two known poly-l-proline helical forms, right-handed all-cis(Form I) and left-handed all-trans (Form II), were determined in the crystalline state by using an approach that combines terahertz time-domain spectroscopy, X-ray diffraction, and solid-state density functional theory. Contrary to expectations, the helices were found to be considerably less rigid than many other natural and synthetic polymers, as well as differing greatly from each other, with Young's moduli of 4.9 and 9.6 GPa for Forms I and II, respectively.

Abstract-Direct measurement of molecular mobility and crystallisation of amorphous pharmaceuticals using terahertz spectroscopy

• Juraj Sibik, 
• J. Axel Zeitler  

• Department of Chemical Engineering and Biotechnology, University of Cambridge, Pembroke Street, Cambridge CB2 3RA, UK

Received 12 October 2015, Revised 23 December 2015, Accepted 24 December 2015, Available online 7 January 2016

http://www.sciencedirect.com/science/article/pii/S0169409X15300272

Despite much effort in the area, no comprehensive understanding of the formation and behaviour of amorphous solids has yet been achieved. This severely limits the industrial application of such materials, including drug delivery where, in principle, amorphous solids have demonstrated their great usefulness in increasing the bioavailability of poorly aqueous soluble active pharmaceutical ingredients. Terahertz time-domain spectroscopy is a relatively novel analytical technique that can be used to measure the fast molecular dynamics of molecules with high accuracy in a non-contact and non-destructive fashion. Over the past decade a number of applications for the characterisation of amorphous drug molecules and formulations have been developed and it has been demonstrated how this technique can be used to determine the onset and strength in molecular mobility that underpins the crystallisation of amorphous drugs. In this review we provide an overview of the history, fundamentals and future perspective of pharmaceutical applications related to the terahertz dynamics of amorphous systems.

Abstract-The Disintegration Process in Microcrystalline Cellulose Based Tablets, Part 1: Influence of Temperature, Porosity and Superdisintegrants

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1. Samy Yassin¹, 
2. Daniel J. Goodwin², 
3. Andrew Anderson², 
4. Juraj Sibik¹, 
5. D. Ian Wilson¹, 
6. Lynn F. Gladden¹ and
7. J. Axel Zeitler^1,*

Article first published online: 12 JUN 2015

DOI: 10.1002/jps.24544

http://onlinelibrary.wiley.com/doi/10.1002/jps.24544/abstract

© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association

Disintegration performance was measured by analysing both water ingress and tablet swelling of pure microcrystalline cellulose (MCC) and in mixture with croscarmellose sodium using terahertz pulsed imaging (TPI). Tablets made from pure MCC with porosities of 10% and 15% showed similar swelling and transport kinetics: within the first 15 s, tablets had swollen by up to 33% of their original thickness and water had fully penetrated the tablet following Darcy flow kinetics. In contrast, MCC tablets with a porosity of 5% exhibited much slower transport kinetics, with swelling to only 17% of their original thickness and full water penetration reached after 100 s, dominated by case II transport kinetics. The effect of adding superdisintegrant to the formulation and varying the temperature of the dissolution medium between 20°C and 37°C on the swelling and transport process was quantified. We have demonstrated that TPI can be used to non-invasively analyse the complex disintegration kinetics of formulations that take place on timescales of seconds and is a promising tool to better understand the effect of dosage form microstructure on its performance. By relating immediate-release formulations to mathematical models used to describe controlled release formulations, it becomes possible to use this data for formulation design. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci

Abstract-Thermal Decoupling of Molecular-Relaxation Processes from the Vibrational Density of States at Terahertz Frequencies in Supercooled Hydrogen-Bonded Liquids

Juraj Sibik , Stephen Elliot , and J Axel Zeitler

J. Phys. Chem. Lett., Just Accepted Manuscript

DOI: 10.1021/jz5007302

Publication Date (Web): May 20, 2014

Copyright © 2014 American Chemical Society

http://pubs.acs.org/doi/abs/10.1021/jz5007302

At terahertz frequencies the libration-vibration motions couple to the dielectric relaxations in disordered hydrogen-bonded solids. The interplay between these processes is still poorly understood, in particular at temperatures below the glass transition temperature, Tg, yet this behaviour is of vital importance for the molecular mobility of such materials to remain in the amorphous phase. A series of polyhydric alcohols have been studied at temperatures between 80 and 310 K in the frequency range of 0.2-3 THz using terahertz time-domain spectroscopy. Three universal features were observed in the dielectric losses, ε''(ν): at temperatures well below the glass transition ε''(ν) comprises a temperature-independent microscopic peak, which persists also into the liquid phase, and which is identified as being due to librational/torsional modes. For 0.65 Tg < T < Tg, additional thermally-dependent contributions are observed and we found strong evidence for its relation to the Johari-Goldstein secondary β-relaxation process. Clear spectroscopic evidence is found for a secondary β glass transition at 0.65 Tg, which is not related to the fragility of the glasses. At temperatures above Tg, the losses become dominated by primary α-relaxation processes. Our results show that the thermal changes in the losses seem to be underpinned by a universal change in the hydrogen bonding structure of the samples.

Abstract-Intrinsic terahertz plasmon signatures in chemical vapour deposited graphene

Shruti Badhwar¹, Juraj Sibik², Piran R. Kidambi³, Harvey E. Beere¹, J. Axel Zeitler³, Stephan Hofmann³, and David A. Ritchie¹

¹Department of Physics, University of Cambridge, Cambridge CB30HE, United Kingdom
²Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB23RA, United Kingdom
³Department of Engineering, University of Cambridge, Cambridge CB30FA, United Kingdom 

http://apl.aip.org/resource/1/applab/v103/i12/p121110_s1?isAuthorized=no

Plasmonic resonance at terahertz (THz) frequencies can be achieved by gating graphene grown via chemical vapour deposition (CVD) to a high carrier concentration. THz time domain spectroscopy of such gated monolayer graphene shows resonance features around 1.6 THz, which appear as absorption peaks when the graphene is electrostatically p-doped and change to enhanced transmission when the graphene is n-doped. Superimposed on the Drude-like frequency response of graphene, these resonance features are related to the inherent poly-crystallinity of CVD graphene. An understanding of these features is necessary for the development of future THz optical elements based on CVD graphene.

© 2013 AIP Publishing LLC

Abstract-Glassy dynamics of sorbitol solutions at terahertz frequencies

http://pubs.rsc.org/en/content/articlelanding/2013/CP/C3CP51936H

Juraj Sibik, Evgenyi Y. Shalaev and J. Axel Zeitler

The absorption spectra of D-sorbitol and a range of its concentrated aqueous solutions were studied by terahertz spectroscopy over the temperature interval of 80 K < T < 310 K. It is shown that the slow-down of molecules at around the glass transition temperature, T_g, dramatically influences the thermal dependence of the absorption at terahertz frequencies. Furthermore, two different absorption regimes are revealed below T_g: at temperatures well below T_g the absorption resembles the coupling of terahertz radiation into the vibrational density of states (VDOS); above these temperatures, between 160 K and T_g, in the sample of pure sorbitol and the sample of a solution of 70wt% sorbitol in water, another type of absorption is observed at terahertz frequencies. Several possibilities of the physical origin of this absorption are discussed and based on the experimental data this process is tentatively assigned to the Johari-Goldstein β-relaxation processes shifting to lower frequencies at temperatures below T_g leaving behind a spectrum largely dominated by losses into the VDOS.