Terahertz Pulsed Imaging and Magnetic Resonance Imaging as Tools to Probe Formulation Stability

Qilei Zhang 1, Lynn F. Gladden 2, Paolo Avalle 3, J. Axel Zeitler 2;* and Michael D. Mantle 2

¹ Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China² Department of Chemical Engineering & Biotechnology, University of Cambridge, Cambridge CB2 3RA, UK³ Merck Sharp & Dohme Ltd., Hoddesdon EN11 9BU, UK

Abstract

Dissolution stability over the entire shelf life duration is of critical importance to ensure the quality of solid dosage forms. Changes in the drug release profile during storage may affect the bioavailability of drug products. This study investigated the stability of a commercial tablet (Lescolr XL) when stored under accelerated conditions (40 ^oC/75% r.h.). Terahertz pulsed imaging (TPI) was used to investigate the structure of the tablet coating before and after the accelerated aging process. The results indicate that the coating was reduced in thickness and exhibited a higher density after being stored under accelerated conditions for four weeks. In situ magnetic resonance imaging (MRI) of the water penetration processes during tablet dissolution in a USP-IV dissolution cell equipped with an in-line UV-vis analyzer was carried out to study local differences in water uptake into the tablet matrix between the stressed and unstressed state. The drug release profiles of the Lescolr XL tablet before and after the accelerated storage stability testing were compared using a “difference” factor ∫1 and a “similarity” factor ∫2. The results reveal that even though the physical properties of the coating layers changed significantly during the stress testing, the coating protected the tablet matrix and the densification of the coating polymer had no adverse effect on the drug release performance.

The TPI studies were performed using TeraView's TPI imaga 2000 system (TeraView, Cambridge, UK) 
Original Article:   http://www.mdpi.com/1999-4923/5/4/591

Position at TeraView - Software Development Specialist (6 month contract)

TeraView Limited is the world's leader in the design and manufacture of terahertz (THz) products to the pharmaceutical, security, medical and materials characterisation markets. Our products continue to yield many ground-breaking applications such as tablet coating thickness and uniformity, cracks, defect analysis, foreign materials and analysis of solid-state structure to be exploited by our customers. Based in Cambridge UK, we have a global client base and a highly-skilled workforce.

We are seeking a Software Development Specialist to join our team; an individual who is able to meet the existing operational needs of the company, as well as planning for the future needs of the company as we grow.

You will have 3 years or more industry experience as a development engineer in scientific or engineering application environments. You will have worked within a formalised Quality System framework, with experience of scientific instrumentation. You must be able to demonstrate a track record of instrumentation or scientific software architecture design. You will be a self-starter with a positive attitude and a proven ability to work in small multi-disciplinary teams.

Role & Responsibilities:

Reporting to the Technical Development Team Leader, your responsibilities will include:

    ·         Design and development of software in support of instrumentation related to our terahertz systems, either individually or as part of a wider team

    ·         Hand-on work in prototyping and implementation of proposed solutions

    ·         Product design and related processes within a formal Quality Management System

Key Skills:

The successful applicant will have:

    ·         Extensive knowledge in at least one object-oriented development platform (C#, C++, Python or comparable)

    ·         A proven track record in the design of multi-threaded hardware/instrumentation control applications, graphical user-interface and desktop application design

    ·         The flexibility to develop across multiple languages / platforms

    ·         A scientific or engineering background

    ·         Experience of product design and related processes within a formal Quality Management System

    ·         Good interpersonal skills and attention to detail

Experience and Education:

Essentials: 

    ·         Computer Science or Engineering degree

    ·         Design and development of scientific measurement equipment, for example spectrometers or imaging systems

    ·         3 years minimum industrial experience in scientific software or instrumentation

    ·         The ability to work alone and on own initiative

    ·         Ability to work in a team

    ·         Flexible approach to work

Desirables: 

    ·         Agile development methodology

    ·         Experience of using boost and STL

    ·         3D & 2D scientific visualisation

    ·         Hardware interfacing experience

    ·         Signal processing, statistics and other data analysis methods

    ·         Knowledge of Matlab or other numerical analysis packages SQL / Relational-database usage

If you think you have the skills and qualities we need, please send your CV, with a covering letter, outlining your current role and remuneration to:

Paddy O’Kelly

Chief Operating Officer

TeraView Limited

Platinum Building

St John’s Innovation Park 

Cambridge CB4 0DS

UK

e-mail: recruitment@teraview.com

No agencies, please.

TeraView offers an excellent salary and benefits package, along with the opportunity for highly-motivated staff to work together and shape the development of products in one of the newest and most exciting areas of technology. We are an equal opportunities employer and pride ourselves on our diverse workforce. For further information and background on the company, please visit our website on: www.teraview.com

The Society for Applied Spectroscopy (SAS) UK Regional Section will hold its 3rd Annual Technical Meeting: “Graphene Spectroscopy”

The Society for Applied Spectroscopy (SAS) UK Regional Section will host its 3^rd Annual Technical Meeting Graphene Spectroscopy on Tuesday 29^th October 2013. This one day meeting will be held at Trinity Hall in Cambridge and will focus on recent advances in the characterization of graphene and two dimensional crystals by spectroscopic methods.

Graphene, thanks to its unique structural and electronic properties, has been called the “miracle material” of the 21st Century. Its isolation in 2004 has sparked a considerable scientific activity that has now established a broad international community with interest ranging from fundamental studies to applications in different fields e.g. composite materials, (opto)electronics, energy, etc. Graphene is just the first of a new class of two dimensional (2d) materials, derived from layered bulk crystals.

Studying and understanding the structure of graphene and 2d crystals is therefore of utmost importance for materials optimization and devices integration. This timely meeting strives to bring together international stakeholders in the field, to give perspectives on the current status of graphene spectroscopy. 

The speakers will be:

Prof. Ping-Heng Tan, Chinese Academy of Sciences, Beijing, P.R. China, “Application of ultra-low frequency Raman spectroscopy in two-dimensional layered materials.”

Prof. Andrea C. Ferrari, Cambridge Graphene Centre, UK, ““Raman Spectroscopy in Graphene: State of the Art” 

Dr. Cinzia Casiraghi, University of Manchester, UK. "Raman spectroscopy of defective graphene: Effect of the excitation energy, type, amount of defects and applied gate voltage."

Dr. Duhee Yoon Cambridge Graphene Centre, UK, “Raman spectroscopy for characterization of strained 
graphene.”

Prof. Günter G. Hoffmann, Eindhoven University of Technology, The Netherlands, “Tip-enhanced Raman Spectroscopy (TERS) and Mapping (TERM) of graphene and related materials”.

Prof. Giulio Cerullo, Politecnico di Milano, Italy. "Ultrafast electron-electron scattering in graphene.”

Prof. Euan Hendry, University of Exeter, UK. "Ultrafast optical measurements of graphene."

Dr. Michael Johnston, University of Oxford, UK. “Terahertz spectroscopy of graphene.”

Dr. Rahul Raveendran-Nair, University of Manchester, UK, “Characterisation of graphene and its chemical derivatives by different spectroscopic techniques.”

[The scientific program for the meeting has been co-organised by Francesco Bonaccorso (CNR-IPCF (Italy) and CGC, Cambridge University) and John Chalmers (SAS UK Regional Section.]

For registration details for this meeting or for more information, please email:

John Chalmers at: vibspecconsult@aol.com or visit: https://sites.google.com/site/sasukregion

Effect of growth temperature on the terahertz-frequency conductivity of the epitaxial transparent conducting spinel NiCo2O4 films

Punam Silwal¹, Chan La-o-vorakiat², Elbert E. M. Chia², Dae Ho Kim³, and Diyar Talbayev¹

¹Department of Physics and Engineering Physics, Tulane University, 6400 Freret Street, New Orleans, LA 70118, USA
²Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore
³Corporate R&D institute, Samsung Electro-Mechanics, 150 Maeyeong-ro, Suwon, Gyunggido 443-743, Korea 

Abstract

We have measured the terahertz-frequency optical conductivity of the epitaxial inverse spinel NiCo₂O₄ films grown at different temperatures. The low-temperature-grown film exhibits a metallic behavior with ferrimagnetic ordering, while the high-temperature-grown film shows greatly suppressed magnetization and insulating behavior. Both films exhibit band-like coherent conduction at intermediate temperatures, albeit with very different carrier densities consistent with the proposed models of cation valencies in this mixed-valence material. Both films also display a crossover to incoherent transport at low temperatures, indicating a disorder-induced tendency toward localization.

The real (ε₁) and imaginary (ε₂) parts of the measured dielectric function of the NCO300 film. 

Two different spectrometers were used for this study: a home-built spectrometer THz-TDS, and a commercial spectrometer mede by Teraview. TeraView's TPS Spectra 3000 was used to perform measurements. 

Preparation, Characterization, and Evaluation of Dipfluzine–Benzoic Acid Co-crystals with Improved Physicochemical Properties

Yulong Lin, Huan Yang, Caiqin Yang, Jing Wang

Pharmaceutical Research September 2013

ABSTRACT

Purpose

To prepare and characterize the co-crystal of dipfluzine and benzoic acid. To investigate the feasibility of the co-crystal for improving solubility and a faster dissolution rate in vitro and evaluate the bioavailability and tissue distribution of co-crystal in vivo.

Methods

A novel dipfluzine–benzoic acid co-crystal prepared using the solvent-assisted co-grinding and the solvent ultrasonic methods were identified and characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), as well as Raman, solid-state nuclear magnetic resonance (ssNMR), and terahertz (THz) spectroscopy. Pharmacokinetics and tissue distribution were tested in vivo using murine models. Statistics analysis for dissolution data of co-crystal in vitro and animal experiment data in vivo were evaluated using t-test.

Results

Results of PXRD and DSC identified the dipfluzine–benzoic acid co-crystals were formed with a molar ratio of 1:2. The IR, Raman, and ssNMR spectra verified the formation of O-H · · · O and O-H · · · F hydrogen bonds. The complex constant, K, was evaluated to be 10⁹ orders of magnitude with Δ_rG < 0. The co-crystal solubility, the rate of drug dissolution and the relative bioavailability were approximately 500 times, five times and double that of dipfluzine, respectively. Increased solubility of co-crystal did not reduce distribution in the brain; the mean concentrations in the brain increased, but the differences had no statistic significance (p > 0.05).

Conclusions

The co-crystal of dipfluzine–benzoic acid improved the physicochemical properties of dipfluzine, such as solubility and dissolution rate. Furthermore, the increased relative bioavailability of co-crystal indicated the potential use in further clinical study.

for full paper see http://link.springer.com/article/10.1007/s11095-013-1181-6#

... Nitrogen, at the flow rate of 20 mL/min, was used as the purging gas, at a flow rate of 20 mL/min. The THz spectra were acquired using a TPI ™ spectra 1,000 transmission spectrometer (TeraView Limited, Cambridge, UK). ...

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