API Determination by NIR Spectroscopy Across Pharmaceutical Production Process

The purpose of this research was to demonstrate the ability of reflectance near-infrared (NIR) spectroscopy for quantitative analysis of an active ingredient in different production steps of a solid formulation. The drug is quantified at two different steps of a pharmaceutical process: after granulation and after tablet coating. Calibration samples were prepared by mixing pure drug, excipients, and batch samples (75–120 mg/g active ingredient) using a simple methodology that can be easily carried out in a laboratory. Partial least squares calibration models were calculated in second-derivative mode using the wavelength range 1,134–1,798 nm. The error of prediction for granulated samples was 1.01% and 1.63% for tablets. The results prove that NIR spectroscopy is a good alternative to other, more time-consuming means of analysis for pharmaceutical process monitoring.     

Reviving near infra‐red emission of Ag2S nanoparticles using interfacial defects in the Ag2S@CdS core–shell structure

Ag₂S@CdS core–shell particles were synthesized with different Cd source content as a measure of shell thickness using a pulsed microwave irradiation method. The particles were verified structurally using X‐ray diffraction, energy dispersive X‐ray analysis and transmission electron microscopy. Optical spectroscopy revealed that core–shells show an absorption peak at 750 nm and an emission peak located around 800 nm after 6 min of microwave irradiation. With continued microwave treatment, the NIR luminescence first vanished but it was revived after 12 min of irradiation, which was 100 nm red shifted. This new type of NIR emission in Ag₂S with sizes greater than 5 nm is due to the proximity of a highly deficient CdS shell with strong red emission that was stable for more than 6 months in water. A mechanism has been suggested for this type of emission.     

Characterization of vitamin B12 compounds in the fruiting bodies of shiitake mushroom (Lentinula edodes) and bed logs after fruiting of the mushroom

This study determined the vitamin B₁₂ content in commercially available dried fruiting bodies of shiitake mushroom, Lentinula edodes. The vitamin B₁₂ contents in dried donko-type fruiting bodies with closed caps (5.61 ± 3.90 μg/100 g dry weight), did not significantly differ from those of dried koushin-type fruiting bodies with open caps (4.23 ± 2.42 μg/100 g dry weight). The bed logs after fruiting of the mushroom also contained the vitamin B₁₂ levels similar to that in the dried shiitake fruiting bodies. To determine whether the dried shiitake fruiting bodies and their bed logs contained vitamin B₁₂ or other corrinoid compounds that are inactive in humans, we purified corrinoid compounds using an immunoaffinity column and identified vitamin B₁₂ using vitamin B₁₂-dependent Escherichia coli 215 bioautograms and liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) chromatograms. Dried shiitake fruiting bodies rarely contained an unnatural corrinoid vitamin B₁₂[c-lactone] that is inactive in humans. Given that shiitake mushroom lacks the ability to synthesize vitamin B₁₂ de novo, the vitamin B₁₂ found in dried shiitake fruiting bodies must have been derived from the bed logs.     

Applicability of near-infrared spectroscopy for process monitoring in bioethanol production

The applicability of near-infrared (NIR) spectroscopy to bioethanol production is investigated. The NIR technique can provide assistance for rapid process monitoring, because organic compounds absorb radiation in the wavelength range 1100–2300 nm. For quantification of a sample's chemical composition, a calibration model is required that relates the measured spectral NIR absorbances to concentrations. For calibration, the concentrations in g/l are determined by the analytical reference method high performance liquid chromatography (HPLC). The calibration models are built and validated for moisture, protein, and starch in the feedstock material, and for glucose, ethanol, glycerol, lactic acid, acetic acid, maltose, fructose, and arabinose in the processed broths. These broths are prepared in laboratory experiments: The ground cereal samples are fermented to alcoholic broths (‘mash’), which are divided into an ethanol fraction and the residual fraction ‘stillage’ by distillation. The NIR technology together with chemometrics proved itself beneficial for fast monitoring of the current state of the bioethanol process, primarily for higher concentrated substances (>1 g/l).     

Application of residual polysaccharide-degrading enzymes in dried shiitake mushrooms as an enzyme preparation in food processing

Objective

To examine the activities of residual enzymes in dried shiitake mushrooms, which are a traditional foodstuff in Japanese cuisine, for possible applications in food processing.

Results

Polysaccharide-degrading enzymes remained intact in dried shiitake mushrooms and the activities of amylase, β-glucosidase and pectinase were high. A potato digestion was tested using dried shiitake powder. The enzymes reacted with potato tuber specimens to solubilize sugars even under a heterogeneous solid-state condition and that their reaction modes were different at 38 and 50 °C.

Conclusion

Dried shiitake mushrooms have a potential use in food processing as an enzyme preparation.

     

Near infrared spectroscopy and aquaphotomics: Novel approach for rapid in vivo diagnosis of virus infected soybean

Near infrared spectroscopy with aquaphotomics as a novel approach was assessed for the diagnosis of soybean plants (Glycine max) infected with soybean mosaic virus (SMV) at latent symptomless stage of the disease. Near infrared (NIR) leaf spectra (in the range of 730-1025 nm) acquired from soybean plants with and without the inoculation of SMV were used. Leaf samples from all plants were assayed with enzyme-linked immunosorbent assay (ELISA) to confirm the infection. Previously reported NIR band for water at 970 nm and two new bands at 910 nm and 936 nm in the water specific region of NIR were found to be markedly sensitive to the SMV infection 2 weeks prior to the appearance of visual symptoms on infected leaves. The spectral calibration model soft independent modeling of class analogy (SIMCA), predicted the disease with 91.6% sensitivity and 95.8% specificity when the second order derivative of the individual plant averaged spectra were used. The study shows the potential of NIR spectroscopy with its novel approach to elucidate latent biochemical and biophysical information of an infection as it allowed successful discrimination of SMV infected plant from healthy at the early symptomless stage of the disease.     

Classification of rhizosphere components using visible–near infrared spectral images

To establish new techniques for automatic classification of rhizosphere components, we investigated the utility of visible (VIS) and near–infrared (NIR) spectral images of the rhizosphere under two soil moisture conditions (mean volumetric water content: 0.39 and 0.16 cm³ cm^?3). Spectral reflectance images of the belowground parts of hybrid poplar cuttings (Populus deltoides × P. euramericana, I45/51) grown in a rhizobox were recorded at 120 spectral bands ranging from 480 to 972 nm. We examined which wavelengths were suitable and the number of spectral bands needed to accurately classify live roots of four age classes, dead roots, leaf mold, and soil. VIS reflectance (<700 nm) of live roots first increased and then decreased with age, whereas NIR reflectance (≥700 nm) was stable in mature roots. The reflectance of dead roots was lower than that of mature roots in both the VIS and NIR spectral regions. VIS reflectance did not differ among dead roots, leaf mold, and soil, but the NIR reflectance was clearly lower in soil than in the other materials. The reflectance of leaf mold and soil increased mainly in the NIR spectral region with reducing soil moisture, but this increase did not affect the order of reflectance intensity among the rhizosphere components in general. Although the most suitable spectral bands statistically selected for classifying rhizosphere components differed somewhat between moist and dry conditions, the spectral bands 580–679 nm (VIS) and 848–894 nm (NIR) provided high reliability under both conditions. Classification accuracy was higher when using two to five VIS–NIR images (overall accuracy ≥87.8%) than three VIS images (red, green, and blue; accuracy <67.1%). The high accuracy with VIS–NIR was mainly due to successful separation of leaf mold and soil. Irrespective of soil moisture condition, the overall accuracy tended to be stable at 92–94% with use of four VIS–NIR images. The spectral bands effective in wet soil conditions could also be used for classification in dry conditions, with overall accuracies >86.9%. These results suggest that automatic image analysis using VIS–NIR images at four spectral bands, including red and NIR, allows for accurate classification of the growth stage or live/dead status of roots and distinguishes between leaf mold and soil.     

Computed tomography for in vivo deep over‐1000 nm near‐infrared fluorescence imaging

This study aims to develop a novel cross‐sectional imaging of fluorescence in over‐1000 nm near‐infrared (OTN‐NIR), which allows in vivo deep imaging, using computed tomography (CT) system. Cylindrical specimens of composite of OTN‐NIR fluorophore, NaGdF₄ co‐doped with Yb³⁺ and Ho³⁺ (ex: 980 nm, em: 1150 nm), were embedded in cubic agar (10.5–12 mm) or in the peritoneal cavity of mice and placed on a rotatable stage. When the fluorescence from inside of the samples was serially captured from multiple angles, the images were disrupted by the reflection and refraction of emitted light on the sample‐air interface. Immersing the sample into water filled in a rectangular bath suppressed the disruption at the interface and successfully reconstructed the position and concentration of OTN‐NIR fluorophores on the cross‐sectional images using a CT technique. This is promising as a novel three‐dimensional imaging technique for OTN‐NIR fluorescent image projections of small animals captured from multiple angles.     

Photobiomodulation of human adipose-derived stem cells using 810 nm and 980 nm lasers operates via different mechanisms of action

Photobiomodulation (PBM) using red or near-infrared (NIR) light has been used to stimulate the proliferation and differentiation of adipose-derived stem cells. The use of NIR wavelengths such as 810 nm is reasonably well accepted to stimulate mitochondrial activity and ATP production via absorption of photons by cytochrome c oxidase. However, the mechanism of action of 980 nm is less well understood. Here we study the effects of both wavelengths (810 nm and 980 nm) on adipose-derived stem cells in vitro. Both wavelengths showed a biphasic dose response, but 810 nm had a peak dose response at 3 J/cm² for stimulation of proliferation at 24 h, while the peak dose for 980 nm was 10–100 times lower at 0.03 or 0.3 J/cm². Moreover, 980 nm (but not 810 nm) increased cytosolic calcium while decreasing mitochondrial calcium. The effects of 980 nm could be blocked by calcium channel blockers (capsazepine for TRPV1 and SKF96365 for TRPC channels), which had no effect on 810 nm. To test the hypothesis that the chromophore for 980 nm was intracellular water, which could possibly form a microscopic temperature gradient upon laser irradiation, we added cold medium (4 °C) during the light exposure, or pre-incubated the cells at 42 °C, both of which abrogated the effect of 980 nm but not 810 nm. We conclude that 980 nm affects temperature-gated calcium ion channels, while 810 nm largely affects mitochondrial cytochrome c oxidase.     

Algorithm-based artifact reduction in patients with arms-down positioning in computed tomography

PurposeArm-artifact, a type of streak artifact frequently observed in computed tomography (CT) images obtained at arms-down positioning in polytrauma patients, is known to degrade image quality. This study aimed to develop a novel arm-artifact reduction algorithm (AAR) applied to projection data.MethodsA phantom resembling an adult abdomen with two arms was scanned using a 16-row CT scanner. The projection data were processed by AAR, and CT images were reconstructed. The artifact reduction for the same phantom was compared with that achieved by two latest iterative reconstruction (IR) techniques (IR1 and IR2) using a normalized artifact index (nAI) at two locations (ventral and dorsal side). Image blurring as a processing side effect was compared with IR2 of the model-based IR using a plastic needle phantom. Additionally, the projection data of two clinical cases were processed using AAR, and the image noise was evaluated.ResultsAAR and IR2 significantly reduced nAI by 87.5% and 74.0%, respectively at the ventral side and 84.2% and 69.6%, respectively, at the dorsal side compared with each filtered back projection (P < 0.01), whereas IR1 did not. The proposed algorithm mostly maintained the original spatial resolution, compared with IR2, which yielded apparent image blurring. The image noise in the clinical cases was also reduced significantly (P < 0.01).ConclusionsAAR was more effective and superior than the latest IR techniques and is expected to improve the image quality of polytrauma CT imaging with arms-down positioning.     

Optical analysis of RE3+ (RE = Pr3+, Er3+ and Nd3+):cadmium lead boro tellurite glasses

This article reports on the optical characterization of Pr³⁺‐, Er³⁺‐ and Nd³⁺‐doped cadmium lead boro tellurite (CLBT) glasses prepared using the melt quenching method. The visible–near infrared (Vis–NIR) absorption spectra of these glasses were analyzed systematically. On measuring the NIR emission spectra of Er³⁺:CLBT glasses, a broad emission band centered at 1536 nm (⁴I_13/2 → ⁴I_15/2) was observed, as were three NIR emission bands at 900 nm (⁴F_3/2 → ⁴I_9/2), 1069 nm (⁴F_3/2 → ⁴I_11/2) and 1338 nm (⁴F_3/2 → ⁴I_13/2) from Nd³⁺:CLBT glasses and an NIR emission band at 1334 nm (¹G₄ → ³H₅) from Pr³⁺:CLBT glasses at an excitation wavelength (λ_ex) of 514.5 nm (Ar⁺ laser). Copyright © 2016 John Wiley & Sons, Ltd.     

Application of Near-Infrared Spectroscopy in Real-Time Monitoring of Product Attributes of Ribbed Roller Compacted Flakes

This study assessed the utility of near-infrared (NIR) spectroscopy for the real-time monitoring of content uniformity and critical quality attributes (tensile strength, Young’s modulus, and relative density) of ribbed roller compacted flakes made by axially corrugated or ribbed rolls. A custom-built setup was used to capture off-line NIR spectra from the flakes containing micronized chlorpheniramine maleate, microcrystalline cellulose, lactose, and magnesium stearate. The partial least square regression method was employed to build calibration models from these off-line NIR spectra using experimental design and validated using test set validation. During calibration model development, various factors, such as spectral acquisition mode, probe positioning, spectral preprocessing method, and beam size, were investigated to improve the prediction ability of the models. The statistical results obtained for calibration models and their validation revealed that dynamic spectral acquisition and proper probe positioning were very crucial to minimize the incorporation of variability in NIR spectra resulting from the flake’s undulation. Calibration and validation statistics also suggested the importance of selecting appropriate spectral preprocessing method and beam size. In this study, best calibration models resulted from standard normal variate followed by first derivative preprocessed dynamic spectra captured using beam size ~1.2 mm. Best calibration models constructed from off-line NIR spectra were used in real-time analysis of flake attributes. Finally, adequacy of best calibration models was established from real-time prediction results. Overall, with the proposed setup, it was possible to monitor the roller compaction process in real time for various properties associated with the ribbed flakes in a rapid, efficient, and nondestructive manner.     

Zeolitic imidazolate framework-8 (ZIF-8) doped TiZSM-5 and Mesoporous carbon for antibacterial characterization

Drug resistant bacteria affects millions worldwide and remains a serious threat to health care system. The study reports the first application of hybrid nanocomposites based on zeolitic imidazolate framework-8 (ZIF-8) with MFI structured zeolite Ti-ZSM-5 (TiZ5) and mesoporous carbon (MC). The composite was designated as TiZ5/ZIF-8 and MC/ZIF-8 was studied for antibacterial activity. Bioactive components Zn²⁺ and 2-methyl imidazole present in ZIF-8 was found to exert significant antibacterial effect on Escherchia. coli and Staphyloccocus. No other antibiotic drugs are required. For comparative purpose, Fe-BTC MOF (BTC = 1,3,5‐benzenetricarboxylate) was used as second set of nanoformulations (TiZ5/Fe-BTC and MC/Fe-BTC) but showed a lower antibacterial activity. The phase (X-ray diffraction), texture (BET surface area), coordination (DRS-UV–Vis), and morphology (TEM) was investigated. XRD showed the presence of nanosized ZIF-8 over TiZ5 and MC. Surface area calculation using N₂ adsorption isotherm showed a reduction in the micropore surface area of ZIF-8 from 1148 m²/g to 224 m²/g (80%) and an increased meso surface area from 31 m²/g to 59 m²/g (90%). The mesopore pore volume increased significantly from 0.05 cm³/g to 0.12 m²/g. MC/ZIF-8 showed similar textural modifications. FT-IR spectra and DRS-UV–Vis spectra showed distinct composite formation with TiZ5, while a weak absorption of ZIF-8 observed over MC. TEM revealed the presence of nanocomposite MC/ZIF-8 and TiZ5/ZIF-8 distributed in nanosize ranging between 25 and 50 nm. TiZ5/ZIF-8 showed the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of 0.5 and 1 mg/ml, respectively against E. coli. The MIC and MBC of TiZ5/ZIF-8 against S. aureus were 1 and 2 mg/ml, respectively. MC/ZIF-8 composite had second best antibacterial activity. This study shows that ZIF-8 based composite holds a great potential against E. coli and S. aureus.     

Intercomparison of dose enhancement ratio and secondary electron spectra for gold nanoparticles irradiated by X-rays calculated using multiple Monte Carlo simulation codes

PurposeTargeted radiation therapy has seen an increased interest in the past decade. In vitro and in vivo experiments showed enhanced radiation doses due to gold nanoparticles (GNPs) to tumors in mice and demonstrated a high potential for clinical application. However, finding a functionalized molecular formulation for actively targeting GNPs in tumor cells is challenging. Furthermore, the enhanced energy deposition by secondary electrons around GNPs, particularly by short-ranged Auger electrons is difficult to measure. Computational models, such as Monte Carlo (MC) radiation transport codes, have been used to estimate the physical quantities and effects of GNPs. However, as these codes differ from one to another, the reliability of physical and dosimetric quantities needs to be established at cellular and molecular levels, so that the subsequent biological effects can be assessed quantitatively.MethodsIn this work, irradiation of single GNPs of 50 nm and 100 nm diameter by X-ray spectra generated by 50 and 100 peak kilovoltages was simulated for a defined geometry setup, by applying multiple MC codes in the EURADOS framework.ResultsThe mean dose enhancement ratio of the first 10 nm-thick water shell around a 100 nm GNP ranges from 400 for 100 kVp X-rays to 600 for 50 kVp X-rays with large uncertainty factors up to 2.3.ConclusionsIt is concluded that the absolute dose enhancement effects have large uncertainties and need an inter-code intercomparison for a high quality assurance; relative properties may be a better measure until more experimental data is available to constrain the models.     

Versatile near-infrared fluorescent probe for in vivo detection of Aβ oligomers

Amyloid-β oligomers (AβOs) enrichment in brain is highly related to Alzheimer’s pathogenesis, but tracing them in the brain by imaging technique is still a great challenge due to their heterogeneity and metastability. Herein, a new near-infrared (NIR) fluorescent probe, namely, PTO-41, was designed and synthesized to specifically target AβOs. PTO-41 possesses excellent functional properties including optimal fluorescent properties (emission maxima at 680 nm upon interacting with AβOs), high affinity (K_d = 349 nM), low cell toxicity, desirable lipophilicity (log P = 2.24), and fast wash out from the brain (brain_{2 min}/brain_{60 min} = 5.0). Furthermore, PTO-41 exhibits a high sensitivity toward AβOs in vitro phantom imaging experiments. More importantly, PTO-41 shows great capacity to differentiate between 4-month-old APP/PS1 model mice from age-matched control mice using in vivo imaging. In summary, PTO-41 almost meets all the requirements as a versatile NIR fluorescent probe for the detection of AβOs both in vitro and in vivo.     

Optical parameters of leaves of 30 plant species

Optical parameters (absorption coefficient k, infinite reflectance R∞, scattering coefficient 8) are tabulated for seven wavelengths and analyzed for statistical differences for 30 plant species. The wavelengths are: 550 nm (green reflectance peak), 650 nm (chlorophyll absorption band), 850 nm (infrared reflectance plateau), 1450 nm (water absorption band), 1650 nm (reflectance peak following water absorption band at 1450 nm), 1950 nm (water absorption band), and 2200 nm (reflectance peak following water absorption band at 1950 nm).     

Growth induced translocation effectively directs an amino acid analogue to developing zones in Agaricus bisporus

The vegetative mycelium of Agaricus bisporus supplies developing white button mushrooms with water and nutrients. However, it is not yet known which part of the mycelium contributes to the feeding of the mushrooms and how this depends on growth conditions. Here we used photon counting scintillation imaging to track translocation of the ¹⁴C-radiolabeled metabolically inert amino acid analogue α-aminoisobutyric acid (¹⁴C-AIB). Translocation to the periphery of the mycelium was observed in actively growing vegetative mycelium with a velocity of up to 6.6 mm h⁻¹, which was 30-fold higher than the growth rate. Furthermore, ¹⁴C-AIB translocated to neighboring colonies after fusion by anastomosis depending on the relative growth rate in these colonies. When mushrooms started to develop, translocation of ¹⁴C-AIB was redirected to the fruiting bodies via mycelium and hyphal cords. More abundant mycelial cord formation and a 5-fold higher rate of translocation was observed for cultures growing directionally from inoculum located at one side of the substrate, when compared to non-directional growth (inoculum mixed throughout the substrate). The maximum translocation distance was also greater (≥50 and 22 cm, respectively). In conclusion, ¹⁴C-AIB translocation switches between vegetative growth and towards developing mushrooms, especially via cords and when source–sink relationships change.     

Monte Carlo kilovoltage X-ray tube simulation: A statistical analysis and compact simulation method

IntroductionMonte Carlo (MC) simulations are a powerful tool for improving image quality in X-ray based imaging modalities. An accurate X-ray source model is essential to MC modeling for CBCT but can be difficult to implement on a GPU while maintaining efficiency and memory limitations. A statistical analysis of the photon distribution from a MC X-ray tube simulation is conducted in hopes of building a compact source model.Materials & methodsMC simulations of an X-ray tube were carried out using BEAMnrc. The resulting photons were sorted into four categories: primary, scatter, off-focal radiation (OFR), and both (scatter and OFR). A statistical analysis of the photon components (energy, position, direction) was completed. A novel method for a compact (memory efficient) representation of the PHSP data was implemented and tested using different statistical based linear transformations (PCA, ZCA, ICA), as well as a geometrical transformation.ResultsThe statistical analysis showed all photon groupings had strong correlations between position and direction, with the largest correlation in the primary data. The novel method was successful in compactly representing the primary (error < 2%) and scatter (error < 6%) photon groupings by reducing the component correlations.Discussion & conclusionStatistical linear transforms provide a method of reducing the memory required to accurately simulate an X-ray source in a GPU MC system. If all photon types are required, the proposed method reduces the memory requirements by 3.8 times. When only primary and scatter data is needed, the memory requirement is reduced from gigabytes to kilobytes.     

The convenient use of fluorescamine for spectrofluorimetric determination of midodrine hydrochloride in pure form and its tablets formulation: Application to content uniformity testing

A novel sensitive and simple spectrofluorimetric method was developed then validated for determination of midodrine in both its authentic pure form and its tablets. This method is based on the reaction between midodrine's aliphatic primary amine moiety with fluorescamine reagent, using borate buffer at pH 7.8 and yielding a highly fluorescent product whose fluorescence intensity was measured at 462 nm after excitation at 388 nm. This method represents the first attempt for determination of midodrine spectrofluorimetrically. A calibration curve was constructed showing that the linear range was 0.2–3.0 μg/ml. The limit of detection and limit of quantitation values were 0.06 and 0.19 μg/ml respectively. The correlation coefficient (r) and the determination coefficient (r²) values were 0.9992 and 0.9984 respectively. The proposed method was validated according to ICH guidelines and successfully applied for determination of midodrine in its tablets with an overall % recovery of 99.56 ± 0.95. Finally, the presented method was adapted to study the content uniformity test according to United States Pharmacopeia guidelines.