Characterization of Crystalline Phase‐Transformations in Theophylline by Time‐Domain Terahertz Spectroscopy

Upadhya, P. C.; Nguyen, K.L.; Shen, Yaochun; Obradovic, Jelena; Fukushige, K.; Griffiths, Ross W.; Gladden, Lynn F.; Davies, A. G.; Linfield, E. H.

doi:10.1080/00387010600636916

Cited by 43 publications

(27 citation statements)

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“…Upadhya and colleagues studied the different solid-state forms of theophylline and characterised solid-solid transformations of anhydrous theophylline between 4 K up to 523 K using terahertz time-domain spectroscopy. [114] In all three studies, a detailed interpretation of the spectral changes that occurred during conversion of the respective API was difficult since the phonon modes and hydrogen-bonding vibrations recorded in the terahertz spectra could not be assigned to specific molecular structures because of the general lack of knowledge about interpreting bands in terahertz spectra. (a) (b) Figure 2 Terahertz absorption spectra of carbamazepine form III during temperature dependent terahertz pulsed spectroscopy measurements.…”

Section: Nir Spectroscopymentioning

confidence: 99%

“…Conversions induced by heating, milling, exposure to water, tableting, dry storage IR spectroscopy Carbamazepine [75] Polymorphic transformation of carbamazepine form III to form I Heating TPS Five forms of sulfathiazole [113] Polymorphic transformation between different polymorphic forms Heating TPS Theophylline [114] Polymorphic transformations of polycrystalline theophylline Heating TPS API, active pharmaceutical ingredient; DSC, differential scanning calorimetry; DRIFTS, diffuse reflectance Fourier transform infrared spectroscopy; FTIR, Fourier transform infrared; IR, infrared; NIR, near infrared; TPS, terahertz pulsed spectroscopy.…”

Section: Heatingmentioning

confidence: 99%

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Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

et al. 2009

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Objectives Solid-state transformations may occur during any stage of pharmaceutical processing and upon storage of a solid dosage form. Early detection and quantification of these transformations during the manufacture of solid dosage forms is important since the physical form of an active pharmaceutical ingredient can significantly influence its processing behaviour, including powder flow and compressibility, and biopharmaceutical properties such as solubility, dissolution rate and bioavailability. Key findings Vibrational spectroscopic techniques such as infrared, near-infrared, Raman and, most recently, terahertz pulsed spectroscopy have become popular for solidstate analysis since they are fast and non-destructive and allow solid-state changes to be probed at the molecular level. In particular, Raman and near-infrared spectroscopy, which require no sample preparation, are now commonly used coupled to fibreoptic probes and are able to characterise solid-state conversions in-line. Traditionally, uni-or bivariate approaches have been used to analyse spectroscopic data sets; however, recently the simultaneous detection of several solid-state forms has been increasingly performed using multivariate approaches where even overlapping spectral bands can be analysed. Summary This review discusses the applications of different vibrational spectroscopic techniques to detect and monitor solid-state transformations possible for crystalline polymorphs, hydrates and amorphous forms of pharmaceutical compounds. In this context, the theoretical basis of solid-state transformations and vibrational spectroscopy and common experimental approaches are described, including recent methods of data analysis.

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Section: Nir Spectroscopymentioning

confidence: 99%

Section: Heatingmentioning

confidence: 99%

Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

et al. 2009

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“…The spectrum of the fresh CrO x /Al 2 O 3 was subtracted from the spectra measured during the reaction, hence the final spectra represent only the adsorbed species on the catalyst surface. THz-TDS measurements were performed at 293 K using an experimental set-up described previously 32,33 . Samples were prepared by mixing 50 mg of catalyst with 150 mg of polyethylene (Sigma-Aldrich) which is transparent to THz radiation.…”

Section: Catalytic Activity Measurementsmentioning

confidence: 99%

A new perspective on catalytic dehydrogenation of ethylbenzene: the influence of side-reactions on catalytic performance

Sanz

McMillan

McGregor

et al. 2015

Catal. Sci. Technol.

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eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. Takedown AbstractThe dehydrogenation of ethylbenzene to styrene is a highly important industrial reaction and the focus of significant research in order to optimise the selectivity to styrene and minimise catalyst deactivation. The reaction itself is a complex network of parallel and consecutive processes including cracking, steam-reforming and reverse water-gas shift (RWGS) in addition to dehydrogenation. The goal of this investigation is to decouple the major processes occurring and analyse how side-reactions affect both the equilibrium of ethylbenzene dehydrogenation and the surface chemistry of steam reforming activity over the reduced catalyst; and reverse water-gas shift reaction. Each of these processes plays a critical role in the observed catalytic activity.Notably, the presence of CO 2 evolved from the reduction of chromium by ethylbenzene and from the gasification of the deposited oxygen-functionalised coke results in the dehydrogenation reaction becoming partially oxidative, i.e. selectivity to styrene is enhanced by coupling of ethylbenzene dehydrogenation with the reverse water-gas shift reaction. Ethylbenzene cracking, coke gasification, steam-reforming and reverse water-gas-shift determine the relative quantities of CO 2 , CO, H 2 and H 2 O and hence affect the coupling of the reactions. Coke deposition during the cracking period lowers the catalyst acidity and may contribute to chromium reduction, hence diminishing the competition between acid and metal sites and favouring dehydrogenation activity.

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“…[10][11][12] Crystalline APIs also have unique phonon modes, and as such, polymorphic forms of solid formulations have different THz spectra. [13][14][15][16] In addition, the absence of distinct modes in amorphous or liquid crystalline forms has been demonstrated. [17][18][19] Thus, THz spectroscopy is thought to be an effective tool for readily discriminating polymorph, even when their crystalline structures are quite similar.…”

Section: -7)mentioning

confidence: 99%

A Novel Analytical Method for Pharmaceutical Polymorphs by Terahertz Spectroscopy and the Optimization of Crystal Form at the Discovery Stage

et al. 2010

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Crystal polymorphs are defined as substances that are chemically identical but exist in more than one crystal form, and generally differ in physicochemical properties. The polymorphism is a common phenomenon among pharmaceuticals. It has been shown that about 80% of active pharmaceutical ingredients (API) have polymorphs. 1,2)The optimization of polymorphic forms of an API is an important area of physicochemical research in drug discovery. The impact of polymorphs has been widely reported in the literatures, affecting such properties as dissolution rates, solubility, bioavailability and manufacturability. 3-7)The detection of polymorphs in drug discovery and manufacturing process is very important for assuring sufficient quality of the API. Powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), IR spectroscopy, Raman spectroscopy and solid state NMR measurement are generally applied for polymorph analysis of APIs. Although most of polymorphs are identifiable by these analytical techniques, there are some difficult cases to identify.In a previous paper, 8) we reported on remarkably similar polymorphs, forms A and B of Compound A, which is a novel drug for the treatment of osteoporosis. They were discriminated only by high-resolution powder X-ray diffractometry and thermally stimulated current (TSC) measurements. In particular, the TSC technique was useful for the discrimination of Compound A polymorphs, since both forms gave completely different TSC patterns.The terahertz (THz) region of the electromagnetic spectrum lies between the infrared and millimeter wave regions around 0.3 to 10 THz. THz spectroscopic analysis has been proposed as an analytical technique for crystal polymorphs because of the typical energies characterizing intermolecular interactions in a crystal lattice correspond to the THz region.9) The assignment of spectral features in this regime is still subject to scientific debate and several experiments have been discussed. [10][11][12] Crystalline APIs also have unique phonon modes, and as such, polymorphic forms of solid formulations have different THz spectra. [13][14][15][16] In addition, the absence of distinct modes in amorphous or liquid crystalline forms has been demonstrated. [17][18][19] Thus, THz spectroscopy is thought to be an effective tool for readily discriminating polymorph, even when their crystalline structures are quite similar.In this paper, we demonstrate THz spectroscopy as a novel analytical procedure for the determination of pharmaceutical polymorphs. We have shown that polymorphs of tolbutamide, carbamazepine and Compound A show slight different THz absorption spectra from each other and the second derivative of the THz absorption spectrum is an enormously beneficial tool for discerning different polymorphs.After the polymorph characterization, the optimization of the crystal form is an important step in the development of an API. To avoid the polymorph trouble during manufacturing and storage such as in the Ritonavir nightmare, 20,21) from the view...

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Characterization of Crystalline Phase‐Transformations in Theophylline by Time‐Domain Terahertz Spectroscopy

Cited by 43 publications

References 21 publications

Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

A new perspective on catalytic dehydrogenation of ethylbenzene: the influence of side-reactions on catalytic performance

A Novel Analytical Method for Pharmaceutical Polymorphs by Terahertz Spectroscopy and the Optimization of Crystal Form at the Discovery Stage

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