scholarly journals Cocrystal Formation through Solid-State Reaction between Ibuprofen and Nicotinamide Revealed Using THz and IR Spectroscopy with Multivariate Analysis

Crystals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 760
Author(s):  
Sae Ishihara ◽  
Yusuke Hattori ◽  
Makoto Otsuka ◽  
Tetsuo Sasaki
Keyword(s):  
Ir Spectroscopy ◽  
Solid Phase ◽  
Time Dependent ◽  
Multivariate Curve Resolution ◽  
Thz Spectroscopy ◽  
Water Molecules ◽  
Active Pharmaceutical Ingredients ◽  
Curve Resolution ◽  
Pharmaceutical Ingredients ◽  
Solid Phase Reactions

Cocrystallisation can enhance the solubility and bioavailability of active pharmaceutical ingredients (APIs); this method may be applied to improve the availability of materials that were previously considered unsuitable. Terahertz (THz) spectroscopy provides clear, substance-specific fingerprint spectra; the transparency of the THz wave allows us to probe inside a sample to identify medicinal materials. In this study, THz and infrared (IR) spectroscopy were used to characterise cocrystallisation in solid-phase reactions between ibuprofen and nicotinamide. Multivariate curve resolution with alternating least squares (MCR-ALS) was applied to both time-dependent THz and IR spectra to identify the intermolecular interactions between these cocrystallising species. The analytical results revealed cocrystal formation through a two-step reaction, in which the steps were dominated by thermal energy and water vapour, respectively. We infer that the presence of water molecules significantly lowered the activation energy of cocrystal formation.

PHARMACEUTICAL FORMULATION MANUFACTURER DISCRIMINATION BY INFRARED SPECTROSCOPY AND PRINCIPAL COMPONENT ANALYSIS

2019 ◽  
pp. 7-15
Author(s):  
E.M. Basova ◽  
Yu.N. Litvinenko ◽  
N.А. Polotnyanko
Keyword(s):  
Principal Component Analysis ◽  
Infrared Spectroscopy ◽  
Ir Spectroscopy ◽  
Principal Component ◽  
Component Analysis ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
The Third ◽  
Chemometric Technique ◽  
Tablet Formulations

In the present work Fournier transform infrared (IR) spectroscopy in association with chemometric technique was employed to identify kind of tablet formulations containing paracetamol and/or caffeine as active pharmaceutical ingredients. 13 samples of 5 commercially available brand tablets of different manufacturers and batches were bayed in local pharmacies. IR spectra of samples were recorded in the range 600—4000 cm-1 and subjected to and principal component analysis (PCA) which allowed to clearly identify 5 clusters in the scores plot using the third and the second principal components, corresponding to the brands of tablets. For Paracetamol and Caffeine-sodium benzoate tablets the combination of IR spectroscopy and PCA was able to recognize the manufacturer on the basis of distance between samples in clusters in the PCA scores plot.

scholarly journals Aspartate/asparagine-β-hydroxylase: a high-throughput mass spectrometric assay for discovery of small molecule inhibitors

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lennart Brewitz ◽  
Anthony Tumber ◽  
Inga Pfeffer ◽  
Michael A. McDonough ◽  
Christopher J. Schofield
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
High Throughput ◽  
Solid Phase ◽  
Hypoxia Inducible Factor ◽  
Active Pharmaceutical Ingredients ◽  
Inhibition Assay ◽  
Pharmaceutical Ingredients ◽  
Epidermal Growth ◽  
Good Signal

AbstractThe human 2-oxoglutarate dependent oxygenase aspartate/asparagine-β-hydroxylase (AspH) catalyses the hydroxylation of Asp/Asn-residues in epidermal growth factor-like domains (EGFDs). AspH is upregulated on the surface of malign cancer cells; increased AspH levels correlate with tumour invasiveness. Due to a lack of efficient assays to monitor the activity of isolated AspH, there are few reports of studies aimed at identifying small-molecule AspH inhibitors. Recently, it was reported that AspH substrates have a non-canonical EGFD disulfide pattern. Here we report that a stable synthetic thioether mimic of AspH substrates can be employed in solid phase extraction mass spectrometry based high-throughput AspH inhibition assays which are of excellent robustness, as indicated by high Z’-factors and good signal-to-noise/background ratios. The AspH inhibition assay was applied to screen approximately 1500 bioactive small-molecules, including natural products and active pharmaceutical ingredients of approved human therapeutics. Potent AspH inhibitors were identified from both compound classes. Our AspH inhibition assay should enable the development of potent and selective small-molecule AspH inhibitors and contribute towards the development of safer inhibitors for other 2OG oxygenases, e.g. screens of the hypoxia-inducible factor prolyl-hydroxylase inhibitors revealed that vadadustat inhibits AspH with moderate potency.

scholarly journals DFT Computed Dielectric Response and THz Spectra of Organic Co-Crystals and Their Constituent Components

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 959 ◽  
Author(s):  
Joseph Bennett ◽  
Michaella Raglione ◽  
Shalisa Oburn ◽  
Leonard MacGillivray ◽  
Mark Arnold ◽  
...  
Keyword(s):  
Density Functional ◽  
Biologically Active ◽  
Thz Spectroscopy ◽  
Vibrational Modes ◽  
Active Pharmaceutical Ingredients ◽  
Dft Methods ◽  
Functional Theory ◽  
Biologically Relevant ◽  
Pharmaceutical Ingredients ◽  
Theory And Modeling

Terahertz (THz) spectroscopy has been put forth as a non-contact, analytical probe to characterize the intermolecular interactions of biologically active molecules, specifically as a way to understand, better develop, and use active pharmaceutical ingredients. An obstacle towards fully utilizing this technique as a probe is the need to couple features in the THz regions to specific vibrational modes and interactions. One solution is to use density functional theory (DFT) methods to assign specific vibrational modes to signals in the THz region, coupling atomistic insights to spectral features. Here, we use open source planewave DFT packages that employ ultrasoft pseudopotentials to assess the infrared (IR) response of organic compounds and complex co-crystal formulations in the solid state, with and without dispersion corrections. We compare our DFT computed lattice parameters and vibrational modes to experiment and comment on how to improve the agreement between theory and modeling to allow for THz spectroscopy to be used as an analytical probe in complex biologically relevant systems.

Raman and Terahertz Spectroscopic Characterization of Solid-state Cocrystal Formation within Specific Active Pharmaceutical Ingredients

2020 ◽  
Vol 26 (38) ◽  
pp. 4829-4846
Author(s):  
Yong Du ◽  
Jiadan Xue ◽  
Zhi Hong
Keyword(s):  
Solid State ◽  
Drug Research ◽  
Terahertz Spectroscopy ◽  
Spectroscopic Characterization ◽  
Time Dependent ◽  
Active Pharmaceutical Ingredients ◽  
Covalent Bonds ◽  
Pharmaceutical Ingredients ◽  
Kinetic Information

: Cocrystallization of specific active pharmaceutical ingredients (APIs) in the solid-state phase is becoming a feasible way to improve their corresponding physicochemical properties and ultimate bioavailability without making and breaking any covalent bonds within them. Many recent reports deal with the characterization and analysis topics of pharmaceutical APIs-based cocrystals. In this mini-review, we will focus on the recent steady-state and time-dependent spectroscopic investigation into the cocrystallization of specific APIs based on both Raman and emerging terahertz spectroscopy in pharmaceutical fields. Distinctive spectral, structural and also kinetic information of pharmaceutical APIs-based cocrystals are obtained and discussed, which would highlight the potential of vibrational spectroscopy as an attractive technique for various drug research and development during cocrystallization of specific APIs.

scholarly journals Assembling the Puzzle of Taxifolin Polymorphism

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5437
Author(s):  
Roman P. Terekhov ◽  
Irina A. Selivanova ◽  
Nonna A. Tyukavkina ◽  
Igor R. Ilyasov ◽  
Anastasiya K. Zhevlakova ◽  
...  
Keyword(s):  
Crystal Engineering ◽  
Solid Phase ◽  
Active Pharmaceutical Ingredients ◽  
Amorphous Substance ◽  
X Ray ◽  
Pharmaceutical Ingredients ◽  
Solid States ◽  
Polymorphic Modifications ◽  
Xrpd Patterns ◽  
Scanning Electron

A large amount of the current literature dedicated to solid states of active pharmaceutical ingredients (APIs) pays special attention to polymorphism of flavonoids. Taxifolin (also known as dihydroquercetin) is an example of a typical flavonoid. Some new forms of taxifolin have been reported previously, however it is still unclear whether they represent polymorphic modifications. In this paper, we tried to answer the question about the taxifolin polymorphism. Taxifolin microtubes and taxifolin microspheres were synthesized from raw taxifolin API using several methods of crystal engineering. All forms were described with the help of spectral methods, scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and thermal analysis (TA). SEM reveals that the morphology of the solid phase is very specific for each sample. Although XRPD patterns of raw taxifolin and microtubes look similar, their TA profiles differ significantly. At the same time, raw taxifolin and microspheres have nearly identical thermograms, while XRPD shows that the former is a crystalline and the latter is an amorphous substance. Only the use of complex analyses allowed us to put the puzzle together and to confirm the polymorphism of taxifolin. This article demonstrates that taxifolin microtubes are a pseudopolymorphic modification of raw taxifolin.

Time-Resolved Step-Scan FT-IR Spectroscopy:  Focus on Multivariate Curve Resolution

2003 ◽  
Vol 43 (6) ◽  
pp. 1966-1973 ◽  
Author(s):  
C. Ruckebusch ◽  
L. Duponchel ◽  
B. Sombret ◽  
J. P. Huvenne ◽  
J. Saurina
Keyword(s):  
Ir Spectroscopy ◽  
Multivariate Curve Resolution ◽  
Time Resolved ◽  
Curve Resolution ◽  
Ft Ir ◽  
Ft Ir Spectroscopy
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