Catalysis-Based Fluorometric Method for Semiquantifying Trace Palladium in Sulfur-Containing Compounds and Ibuprofen.

Trace palladium in synthetic materials can be rapidly and inexpensively semiquantified by a catalysis-based fluorometric method that converts resorufin allyl ether to resorufin. However, whether sulfur compounds would interfere with this method has not been systematically studied. Herein, we show that although thiourea in solution interferes with quantification, sulfide, thiol, and thiocarbamate do not. The fluorometric method can also detect palladium bound to sulfur-based scavenger resin and outperform inductively coupled plasma mass spectrometry for detecting trace palladium in ibuprofen.

Environmental risk assessment of pharmaceutical pollutants in the Oro River Sub-basin (Colombia).

Pharmaceuticals and Personal Care Compounds (PPCPs) are contaminants present in wastewater and in the receiving surface waters, which have no regulations and can bring on environmental risks. In this study, we evaluated the presence of six PPCPs in the Oro River Sub-basin (Colombia) and the environmental risk associated with them. We have verified that the monitored rivers show the presence of Ibuprofen, Cephalexin and Carbamazepine; the first ones (Ibuprofen and cephalexin) were those that presented higher concentrations since they are widely prescribed in Colombia. Pharmaceutical compound concentrations in the rivers downstream of the wastewater treatment plants from Floridablanca were higher than in other monitoring sites being a significant point source of contamination. This wastewater treatment plant receives hospital discharges from the city, including internationally recognized clinics accepting patients from different parts of the country. The environmental risk assessment showed that ibuprofen and Cephalexin have a higher impact on aquatic organisms.

Analyzing microbial communities and their biodegradation of multiple pharmaceuticals in membrane bioreactors.

Pharmaceuticals are of concern to our planet and health as they can accumulate in the environment. The impact of these biologically active compounds on ecosystems is hard to predict, and information on their biodegradation is necessary to establish sound risk assessment. Microbial communities are promising candidates for the biodegradation of pharmaceuticals such as ibuprofen, but little is known yet about their degradation capacity of multiple micropollutants at higher concentrations (100 mg/L). In this work, microbial communities were cultivated in lab-scale membrane bioreactors (MBRs) exposed to increasing concentrations of a mixture of six micropollutants (ibuprofen, diclofenac, enalapril, caffeine, atenolol, paracetamol). Key players of biodegradation were identified using a combinatorial approach of 16S rRNA sequencing and analytics. Microbial community structure changed with increasing pharmaceutical intake (from 1 to 100 mg/L) and reached a steady-state during incubation for 7 weeks on 100 mg/L. HPLC analysis revealed a fluctuating but significant degradation (30-100%) of five pollutants (caffeine, paracetamol, ibuprofen, atenolol, enalapril) by an established and stable microbial community mainly composed of Achromobacter, Cupriavidus, Pseudomonas and Leucobacter. By using the microbial community from MBR1 as inoculum for further batch culture experiments on single micropollutants (400 mg/L substrate, respectively), different active microbial consortia were obtained for each single micropollutant. Microbial genera potentially responsible for degradation of the respective micropollutant were identified, i.e. Pseudomonas sp. and Sphingobacterium sp. for ibuprofen, caffeine and paracetamol, Sphingomonas sp. for atenolol and Klebsiella sp. for enalapril. Our study demonstrates the feasibility of cultivating stable microbial communities capable of degrading simultaneously a mixture of highly concentrated pharmaceuticals in lab-scale MBRs and the identification of microbial genera potentially responsible for the degradation of specific pollutants. KEY POINTS: • Multiple pharmaceuticals were removed by stable microbial communities. • Microbial key players of five main pharmaceuticals were identified.

Experimental investigation for treating ibuprofen and triclosan by biosurfactant from domestic wastewater.

The presence of emerging pollutants of pharmaceutical products and personal care products (PPCPs) in the aquatic environment overspreads the threat on living beings. Bioremediation is a promising option for treating wastewater. In the present study, an experimental investigation was carried out to produce a biosurfactant by Pseudomonas aeruginosa (MTCC 1688) for the removal of Ibuprofen (IBU) and Triclosan (TCS) from domestic wastewater. It was performed in three stages. Firstly, the production and optimization of biosurfactant was carried out to arrive at the best combination of crude sunflower oil, sucrose and ammonium bicarbonate (10%: 5.5 g/L: 1 g/L) to yield effective biosurfactant production (crude biosurfactant) and further extended to achieve critical micelle concentration (CMC) formation by dilution (biosurfactant at 10.5%). The stability of the biosurfactant was also confirmed. Biosurfactant showed a reduction in the surface tension to 41 mN/m with a yield concentration of 11.2 g/L. Secondly, its effectiveness was evaluated for the removal of IBU and TCS from the domestic wastewater collected during the dry and rainy seasons. Complete removal of IBU was achieved at 36 h & 6 h and TCS at 6 h & 1 h by crude biosurfactant and biosurfactant at CMC formation for the dry season sample. IBU removal was achieved in 2 h by both crude and biosurfactant at CMC and no TCS was detected in the rainy season sample. Thirdly, biotransformation intermediates of IBU and TCS formed during the application of the biosurfactant and degradation pathways are proposed based on the Liquid Chromatography-Mass Spectrometry (LC-MS) and it indicates that there is no formation of toxic by-products. Based on the results, it is evident that biosurfactant at CMC has performed better for the removal of IBU and TCS than crude biosurfactants without any formation of toxic intermediates. Hence, this study proved to be an eco-friendly, cost-effective and sustainable treatment option for domestic wastewater treatment.

Variable-Temperature NMR Analysis of the Thermodynamics of Polymer Partitioning between Aqueous and Drug-Rich Phases and Its Significance for Amorphous Formulations.

We previously reported that the polymers used in amorphous solid dispersion (ASD) formulations, such as polyvinylpyrrolidone (PVP), polyvinylpyrrolidone/vinyl acetate (PVP-VA), and hypromellose (HPMC), distribute into the drug-rich phase of ibuprofen (IBP) formed by liquid-liquid phase separation, resulting in a reduction in the maximum drug supersaturation in the aqueous phase. Herein, the mechanism underlying the partitioning of the polymer into the drug-rich phase was investigated from a thermodynamic perspective. The dissolved IBP concentration in the aqueous phase and the amount of polymer distributed into the IBP-rich phase were quantitatively analyzed in IBP-supersaturated solutions containing different polymers using variable-temperature solution-state nuclear magnetic resonance (NMR) spectroscopy. The polymer weight ratio in the IBP-rich phase increased at higher temperatures, leading to a more notable reduction of IBP amorphous solubility. Among the polymers, the amorphous solubility reduction was the greatest for the PVP-VA solution at lower temperatures, while HPMC reduced the amorphous solubility to the greatest extent at higher temperatures. The change in the order of polymer impact on the amorphous solubility resulted from the differences in the temperature dependency of polymer partitioning. The van't Hoff plot of the polymer partition coefficient revealed that both enthalpy and entropy changes for polymer transfer into the IBP-rich phase from the aqueous phase (ΔHaqueous→IBP-rich and ΔSaqueous→IBP-rich) gave positive values for most of the measured temperature range, indicating that polymer partitioning into the IBP-rich phase was an endothermic but entropically favorable process. The polymer transfer into the IBP-rich phase was more endothermic for HPMC than for PVP and PVP-VA. The solid-state NMR analysis of the IBP/polymer ASD implied that the newly formed IBP/polymer interactions in the IBP-rich phase upon polymer incorporation were weaker for HPMC, providing a rationale for the larger positive transfer enthalpy for HPMC. The change in Gibbs free energy for polymer transfer (ΔGaqueous→IBP-rich) showed negative values across the experimental temperature range, decreasing with an increase in temperature, indicating that the distribution of the polymer into the IBP-rich phase is favored at higher temperatures. Moreover, ΔGaqueous→IBP-rich for HPMC showed the greatest decrease with the temperature, likely reflecting the temperature-induced dehydration of HPMC in the aqueous phase. This study contributes fundamental insights into the phenomenon of polymer partitioning into drug-rich phases, furthering the understanding of achievable supersaturation levels and ultimately providing information on polymer selection for ASD formulations.

A simple and green liquid chromatography method for the determination of ibuprofen in milk-containing simulated gastrointestinal media for monitoring the dissolution studies of three-dimensional-printed formulations.

A fast and green ultra-high-performance liquid chromatographic method was developed for the determination of ibuprofen in milk-containing simulated gastrointestinal media to monitor the dissolution of three-dimensional printed formulations. To remove interfering compounds, protein precipitation using methanol as a precipitation reagent was performed. The separation of the target analyte was performed on a C18 column using a mobile phase consisting of 0.05% v/v aqueous phosphoric acid solution: methanol, 25:75% v/v. Method validation was conducted using the total error concept. The ß-expectation tolerance intervals did not exceed the acceptance criteria of ±15%, meaning that 95% of future results will be included in the defined bias limits. The relative bias ranged between ─1.1 and +3.2% for all analytes, while the relative standard deviation values for repeatability and intermediate precision were less than 2.8% and 3.9%, respectively. The achieved limit of detection was 0.01 µg/ml and the lower limit of quantitation was established as 2 µg/ml. The proposed method was simple, and it required reduced organic solvent consumption following the requirements of Green Analytical Chemistry. The method was successfully employed for the determination of ibuprofen in real biorelevant media obtained from dissolution studies.

Comparative study on eucalyptol and camphor rich essential oils from rhizomes of Hedychium spicatum Sm. and their pharmacological, antioxidant and antifungal activities.

The aim of present study was to evaluate chemical composition and different biological activities viz., pharmacological and antioxidant activities of essential oils. The chemical composition of essential oils was determined by gas chromatography/mass spectrometry while biological activities were evaluated by standard protocols. Essential oils of Hedychium spicatum Sm. from two different ecological niches viz; Nainital (Site-I) and Himachal Pradesh (Site-II) of India revealed the qualitative and quantitative chemo-diversity. Both the oils were dominated by oxygenated terpenoids. Major marker compounds identified were eucalyptol, camphor, linalool, α-eudesmol, 10-epi-γ-eudesmol, and iso-borneol. Both the oils exhibited anti-inflammatory activity suppressing 17.60 % to 33.57 % inflammation at 100mg/kg b. wt. dose levels compared to ibuprofen-treated group (40.06 %). The sub-acute inflammation in oils-treated mice groups (50 and 100 mg/kg b. wt.) increased on day 2 but showed a gradual decrease from day 3 onwards and then recovered to normal by day 10. The antinociception percentage for doses (50 and 100 mg/kg b. wt.) ranged from 33.70-40.46 % in Site-I and 30.34-42.39 % in Site-II compared to standard drug, ibuprofen (43.08 %). The oils also showed a good antipyretic effect by suppressing Brewer's yeast (Saccharomyces cerevisiae) induced pyrexia after oil dose injection. The oils also exhibited good antioxidant activity.

Ring Vibrations to Sense Anionic Ibuprofen in Aqueous Solution as Revealed by Resonance Raman.

We unravel the potentialities of resonance Raman spectroscopy to detect ibuprofen in diluted aqueous solutions. In particular, we exploit a fully polarizable quantum mechanics/molecular mechanics (QM/MM) methodology based on fluctuating charges coupled to molecular dynamics (MD) in order to take into account the dynamical aspects of the solvation phenomenon. Our findings, which are discussed in light of a natural bond orbital (NBO) analysis, reveal that a selective enhancement of the Raman signal due to the normal mode associated with the C-C stretching in the ring, νC=C, can be achieved by properly tuning the incident wavelength, thus facilitating the recognition of ibuprofen in water samples.

Electroanalysis of Ibuprofen and Its Interaction with Bovine Serum Albumin.

The current work presents a sensitive, selective, cost-effective, and environmentally benign protocol for the detection of ibuprofen (IBP) by an electrochemical probe made of a glassy carbon electrode modified with Ag-ZnO and MWCNTs. Under optimized conditions, the designed sensing platform was found to sense IBP up to a 28 nM limit of detection. The interaction of IBP with bovine serum albumin (BSA) was investigated by differential pulse voltammetry. IBP-BSA binding parameters such as the binding constant and the stoichiometry of complexation were calculated. The results revealed that IBP and BSA form a single strong complex with a binding constant value of 8.7 × 1013. To the best of our knowledge, this is the first example that reports not only IBP detection but also its BSA complexation.

Low-power swept-source Raman spectroscopy.

'Molecular fingerprinting' with Raman spectroscopy can address important problems-from ensuring our food safety, detecting dangerous substances, to supporting disease diagnosis and management. However, the broad adoption of Raman spectroscopy demands low-cost, portable instruments that are sensitive and use lasers that are safe for human eye and skin. This is currently not possible with existing Raman spectroscopy approaches. Portability has been achieved with dispersive Raman spectrometers, however, fundamental entropic limits to light collection both limits sensitivity and demands high-power lasers and cooled expensive detectors. Here, we demonstrate a swept-source Raman spectrometer that improves light collection efficiency by up to 1000× compared to portable dispersive spectrometers. We demonstrate high detection sensitivity with only 1.5 mW average excitation power and an uncooled amplified silicon photodiode. The low optical power requirement allowed us to utilize miniature chip-scale MEMS-tunable lasers with close to eye-safe optical powers for excitation. We characterize the dynamic range and spectral characteristics of this Raman spectrometer in detail, and use it for fingerprinting of different molecular species consumed everyday including analgesic tablets, nutrients in vegetables, and contaminated alcohol. By moving the complexity of Raman spectroscopy from bulky spectrometers to chip-scale light sources, and by replacing expensive cooled detectors with low-cost uncooled alternatives, this swept-source Raman spectroscopy technique could make molecular fingerprinting more accessible.

Amorphous Drug Solubility and Maximum Free Drug Concentrations in Cyclodextrin Solutions: A Quantitative Study Using NMR Diffusometry.

Cyclodextrin (CD) has been widely used as a solubilizing agent for poorly water-soluble drugs. In the present study, the effect of CD on the amorphous drug solubility and the maximum thermodynamic activity of the drug in the aqueous phase when the drug concentration exceeded the liquid-liquid phase separation (LLPS) concentration was investigated using three chemically diverse CDs, ß-cyclodextrin (ß-CD), dimethyl-ß-CD (DM-ß-CD), and hydroxypropyl-ß-CD (HP-ß-CD). The amorphous solubility of ibuprofen (IBP) increased substantially linearly with the increase in the CD concentration due to IBP/CD complex formation. Surprisingly, although the crystalline solubility of IBP in the ß-CD solution reached a plateau at ß-CD concentrations above 3 mM (BS-type solubility diagram) because of the limited crystalline solubility of the IBP/ß-CD complex, the amorphous solubility of IBP increased linearly even when the ß-CD concentration was higher than 3 mM. The amorphous solubility of IBP in CD solutions was influenced primarily by the phase separation of the IBP-supersaturated solution to the aqueous phase and the other phase mainly composed of IBP, namely, the IBP-rich phase, via LLPS. NMR spectroscopy revealed that DM-ß-CD was distributed into the IBP-rich phase when the IBP concentration exceeded its amorphous solubility, while ß-CD and HP-ß-CD showed minimal mixing with the IBP-rich phase. NMR diffusometry showed that the maximum free IBP concentration was reduced in the DM-ß-CD solution compared to that in the buffer. The mixing of DM-ß-CD with the IBP-rich phase reduced the chemical potential of IBP in the IBP-rich phase, which in turn reduced the maximum thermodynamic activity of IBP in the aqueous phase. In contrast, the maximum free IBP concentration was unchanged when ß-CD or HP-ß-CD was present. The hydrophobic nature of the DM-ß-CD substituent may contribute to its partitioning into the IBP-rich phase. The present study highlights the impact of CD on the maximum thermodynamic activity of drugs as well as the apparent amorphous solubility of the drug. This aspect should be considered for improving the effective absorption of poorly water-soluble drugs.

Ultra-rapid capillary zone electrophoresis method for simultaneous determination of arginine and ibuprofen.

The combination of arginine and ibuprofen is widely used for pain relief with a faster onset of action than conventional ibuprofen. Therefore, the determination of both compounds in a single run is highly desirable for rapid quality control applications. This paper reports an ultra-fast method (100 injections/h) for simultaneous determination of arginine and ibuprofen using capillary electrophoresis with capacitively coupled contactless conductivity detection. The separation of arginine as cation and ibuprofen as anion was achieved using a background electrolyte composed by an equimolar mixture of 10 mmol/L of 2-(cyclohexylamino) ethanesulfonic acid and boric acid with pH adjusted to 8.4 using potassium hydroxide. The limits of detections were 5.3 and 10.0 µmol/L for arginine and ibuprofen, respectively. The proposed method is simple, fast (one analysis every 35 s), environmentally friendly (minimal waste generation) and accurate (recovery values between 95 and 98%).

Direct distinction of ibuprofen and flurbiprofen enantiomers by ion mobility mass spectrometry of their ternary complexes with metal cations and cyclodextrins in the gas phase.

Enantiomeric drugs are widely used and play important roles in pharmaceuticals. Ion mobility spectrometry coupled with mass spectrometry technology provides a unique method for distinguishing the enantiomeric drugs, enantiomeric identification, and quantitation in the gas phase. In this study, enantiomeric molecules of ibuprofen and flurbiprofen were clearly recognized by forming host-guest complex ions using trapped ion mobility time-of-flight mass spectrometry. Ternary complex ions can be produced easily by electrospray ionization of the mixed solutions of ibuprofen, cyclodextrins, and CaCl2 , LiCl, or NaCl, as well as flurbiprofen, cyclodextrins, and CaCl2 . The relative contents of different chiral ibuprofens in a mixed solution were also quantitatively measured. This new method is a simple, effective, and a convenient enantioselective analysis method.

Applicability of capillary electrophoresis-frontal analysis for displacement studies: Effect of several drugs on l-tryptophan and lidocaine binding to human serum albumin.

The effective concentration of a drug in the blood, i.e. the concentration of a free drug in the blood, is influenced by the strength of drug binding onto plasma proteins. Besides its efficacy, these interactions subsequently influence the liberation, absorption, distribution, metabolism, excretion, and toxicological properties of the drug. It is important to not only determine the binding strength and stoichiometry, but also the binding site of a drug on the plasma protein molecule, because the co-administration of drugs with the same binding site can affect the above-mentioned concentration and as a result the pharmacological behavior of the drugs and lead to side effects caused by the change in free drug concentration, its toxicity. In this study, the binding characteristics of six drugs with human serum albumin, the most abundant protein in human plasma, were determined by capillary electrophoresis-frontal analysis, and the obtained values of binding parameters were compared with the literature data. The effect of several drugs and site markers on the binding of l-tryptophan and lidocaine to human serum albumin was investigated in subsequent displacement studies which thus demonstrated the usability of capillary electrophoresis as an automated high-throughput screening method for drug-protein binding studies.

Synchronous spectrofluorometric methods for simultaneous determination of diphenhydramine and ibuprofen or phenylephrine in combined pharmaceutical preparations.

Simple and rapid synchronous fluorometric methods were adopted and validated for the simultaneous analysis of a binary mixture of diphenhydramine (DIP) and ibuprofen (IBU) (Mix I) or DIP and phenylephrine (PHE) (Mix II) in their co-formulated pharmaceuticals without prior separation. Analysis of Mix I is based on the measurement of the peak amplitudes (D1 ) of synchronous fluorescence intensities at 265.1 nm for DIP and 260 nm for IBU. The relationship between the concentration and the amplitude of the first-derivative synchronous fluorescence spectra showed good linearity over the concentration ranges 0.50-10.00 µg ml-1 and 0.50-7.90 µg ml-1 for DIP and IBU, respectively. Analysis of Mix II was based on measurement of the peak amplitude (D1 ) synchronous fluorescence intensities at 230 nm for DIP and at 253.9 nm for PHE. Moreover, for Mix II, the peak amplitude (D2 ) synchronous fluorescence intensities were measured at 227.9 nm for DIP and at 264.9 nm for PHE. Calibration plots were rectilinear over the concentration range 0.30-3.50 µg ml-1 and 0.03-0.75 µg ml-1 for DIP and PHE, respectively. The proposed methods were successfully applied to determine the studied compounds in pure form and in pharmaceutical preparations.

Ibuprofen removal by a microfiltration membrane bioreactor during the startup phase.

The behavior of ibuprofen (IBU) during the startup phase of a microfiltration membrane bioreactor (MBR) was determined. A full-scale experimental installation treating real urban wastewater was used for the study. The MBR was composed of an anoxic and an aerobic bioreactors working in pre-denitrification configuration, followed of a membrane reactor. A full mass balance was carried out to estimate the contribution of biotransformation and sorption to biomass to the overall removal of the IBU. During the startup phase of the MBR system there were significant oscillations of the operational variables, mainly of the sludge retention time (SRT); nevertheless, the capacity of the system for IBU removal was very high, with yields of over 94%, despite reaching minimum SRT values of 4.15 d. The main IBU removal occurs in the aerobic reactor, both in the liquid phase and the one associated with the sludge, while in the anoxic bioreactor the removal was scarce, although a certain transfer of IBU from the liquid phase to the sludge took place under anoxic conditions. Despite the high IBU removal yields during startup, the SRT was the most influential variable in IBU removal, an effect observed in all bioreactors, particularly in the anoxic one.

C18-Coated Solid-Phase Microextraction Fibers for the Quantification of Partitioning of Organic Acids to Proteins, Lipids, and Cells.

The effects measured with in vitro cell-based bioassays are typically reported as nominal effect concentrations ( Cnom), but the freely dissolved concentration in the exposure medium ( Cw) and the total cellular concentration ( Ccell) are considered more quantitative dose metrics that allow extrapolation to the whole-organism level. To predict Cw and Ccell, the partitioning of the test chemicals to medium proteins and lipids and cells has to be known. In this study, we developed a solid-phase microextraction (SPME) method based on C18-coated fibers to quantify the partitioning of diclofenac, 2,4-dichlorophenoxyacetic acid (2,4-D), ibuprofen, naproxen, torasemide, warfarin, and genistein to bovine serum albumin (BSA), phospholipid liposomes, fetal bovine serum (FBS), and cells. For ibuprofen, 2,4-D, naproxen, and warfarin, the partitioning to the SPME fibers was found to be concentration dependent, which had to be considered for the calculation of distribution ratios to biological materials. The sorption isotherms to FBS were nonlinear for diclofenac, 2,4-D, ibuprofen, naproxen, and warfarin. The FBS isotherms could be described by assuming that the total amount of chemical bound to FBS is the sum of the amount specifically bound to the binding sites of albumin and nonspecifically bound to all medium proteins and lipids. The determined cell-water distribution ratios ( Dcell/w) differed considerably between four different cell lines (up to 1.83 log-units) and also between different batches of the same cell line (up to 0.48 log-units). The relative importance of protein and lipid content for Dcell/w was evaluated with a mass balance model and different types of cellular proteins and lipids as input parameters. Existing in vitro mass balance models may underestimate Cw because they do not account for saturable protein binding and overestimate Ccell for organic acids, if BSA is used as surrogate for cellular proteins.

Characterization of the 3D microstructure of Ibuprofen tablets by means of synchrotron tomography.

A new methodology to segment the three-dimensional (3D) internal structure of Ibuprofen tablets from synchrotron tomography is presented, introducing a physically coherent trinarization for greyscale images of Ibuprofen tablets consisting of three phases: microcrystalline cellulose, Ibuprofen and pores. For this purpose, a hybrid approach is developed combining a trinarization by means of statistical learning with a trinarization based on a watershed algorithm. This hybrid approach allows us to compute microstructure characteristics of tablets using methods of statistical image analysis. A comparison with experimental results shows that there is a significant amount of pores which is below the resolution limit. At the same time, results from image analysis let us conjecture that these pores constitute the great majority of the surface between pores and solid. Furthermore, we compute microstructure characteristics, which are experimentally not accessible such as local percolation probabilities and chord length distribution functions. Both characteristics are meaningful in order to quantify the influence of tablet compaction on its microstructure. The presented approach can be used to get better insight into the relationship between production parameters and microstructure characteristics based on 3D image data of Ibuprofen tablets manufactured under different conditions and elucidate key effects on the strength and solubility kinetics of the final  formulation. LAY DESCRIPTION: A typical formulation of uniaxial compacted Ibuprofen tablets consist of a mixture of an excipient (microcrystalline cellulose) with an active ingredient (a ground fraction of Ibuprofen). The final mechanical strength of the tablet as well as the release kinetics are strongly influenced by the underlying microstructure, i.e. the spatial arrangement of the microcrystalline cellulose and Ibuprofen within the tablet. In order to optimize the performance of the tablet, it is important to investigate the relationship between its microstructure and the corresponding production parameters. For this purpose, 3D imaging is a powerful tool as it allows computing microstructural properties such as the internal arrangement, interconnectivity and pore location and distribution, characteristics that cannot be computed by experimental characterization techniques. In the present study, a new algorithm for an accurate trinarization of 3D image data obtained by synchrotron tomography is presented. Trinarization means that we reconstruct microcrystalline cellulose, Ibuprofen and pores on the basis of the 3D images, where one can only observe different greyscale values, but not the different constituents themselves. For this purpose, a hybrid approach combining a trinarization by means of artificial intelligence with a trinarization based on a geometrically motivated algorithm is developed. This hybrid approach allows to compute microstructure characteristics of tablets using image analysis. A comparison with experimental results shows that there is a significant amount of pores below the resolution limit. At the same time results from image analysis lead to the conjecture that these pores constitute the major part of the surface between pores and solid. Moreover, characteristics are computed by image analysis, which are meaningful in order to quantify the influence of tablet compaction parameters on its microstructure. The presented novel approach can be used to elucidate the relationship between production parameters and microstructure characteristics based on 3D image data of Ibuprofen tablets manufactured under different mixing, loading and processing conditions.

A highly sensitive and versatile chiral sensor based on a top-gate organic field effect transistor functionalized with thiolated ß-cyclodextrin.

The discrimination of chirality by field effect transistors (FETs) is a great challenge because enantiomers possess exactly identical charge and hence chiral recognition is solely related to spatial effects, while the working principle of most FET sensors is based on the intrinsic charge of analytes. In this work, a chiral organic field effect transistor (COFET) with a self-assembled thiolated ß-cyclodextrin (SH-ß-CD) monolayer modified gold top-gate electrode is developed to afford rapid, highly sensitive and real-time chiral discrimination for various enantiomers. Well-defined sensing results are achieved for diverse acidic enantiomers with the lowest detection concentration (LDC) of 10-12 M. Chiral sensing mostly depends on the changed work function of the top electrode and hence varied surface potential at the gate/solution interface caused by the target-induced CD-enantiomer complex formation with different geometries for each isomer, which is independent of the intrinsic charge of the analytes. This proof-of-concept allows chiral resolution even for uncharged enantiomers, which still remains as a major hurdle for FET-based sensors. Furthermore, the COFET shows composition dependence for its response towards the enantiomer mixture of phenylalanine (Phe) and a "real world" pharmaceutical drug (ibuprofen), which proves the potentiality of the COFET for quantitative chiral analysis of commercial pharmaceutical drugs.

Resolution of (R,S)-ibuprofen catalyzed by immobilized Novozym40086 in organic phase.

The enantioselective esterification of ibuprofen catalyzed by Novozym40086 was successfully conducted in organic solvent. Removing-water reagent was added into the reaction mixture to remove water produced in the esterification. The effects of temperature, n-hexanol concentration, ibuprofen concentration, and loading of enzymes were investigated. Under the condition of equilibrium, the thermodynamic equilibrium constant (K) of 7.697 and enantioselectivity (E) of 8.512 were obtained. The esterification reaction achieved its equilibrium in approximately 30 hours with conversion of 56% and eeS of 93.78%. The predicted values of X and eeS were 67.90% and 95.60%, respectively. The experimental value is approximately equal to the theoretical value, which indicates the feasibility of ideal models.