Ketoprofen Research Articles

The Pattern of NSAIDs Drugs Use by Libyans Patients for Acute Tissue Injury

Introduction: NSAIDs are a family of drugs that have achieved widespread use in sports medicine in both prescription and over-the counter (OTC) forms. NSAIDs are often administered after acute soft tissue injury in an effort to reduce pain and inflammation and thus speed an injured athlete's return to competition. However, recent evidence suggests that the short term benefits of NSAID therapy may adversely affect the long-term healing of injured soft tissues. Method: The study was performed to test pattern of NSAIDs use by Libyan patients. Patients were asked to complete a self-report questionnaires while attending orthopedic clinic at Al-Haraysh hospital at Darna City (Libya) during the period from March to May 2022. Result: Panadol (acetaminophen) consumption was reported by 6 (40%). Equivalent data for ketoprofen (Fastum gel) were 6 (40%) for topical preparation. Tewinty percent (3) of the participants consumed Muscadol (Paracetamol 450mg + Orphenadrine citrate 35mg)-based drugs. These were ibuprofen (ketoprofen)-based drugs used by 3 (20%) of respondent . The 2 (13%) consumed Naproxen (Nopain) and only the 1 (6.6%) used Aspirin for their injuries. Conclusion: NSAIDs are commonly used in the treatment of acute soft tissue injuries in athletes. Because of the diverse of adverse effects associated with NSAIDs, athletic trainers must be aware of the potential benefits and liabilities of NSAIDs use by injured.

Propionic Acid Groups and Multiple Aromatic Rings Induce Binding of Ketoprofen and Naproxen to the Hydrophobic Core of Bovine Serum Albumin.

Ketoprofen (KP), which causes photosensitivity by interacting with serum albumin (SA), and three drugs, ibuprofen (IBP), naproxen (NPX), and diazepam (DZP), which share the same binding site, were investigated for their interaction with bovine SA (BSA). For KP, DZP, and IBP, where drug-concentration-dependent quenching of BSA-intrinsic fluorescence was observed, a modified Stern-Volmer plot showed that dynamic quenching was dominant for KP and static quenching was dominant for DZP and IBP. However, this alone cannot be compared with NPX. Therefore, by performing singular value decomposition (SVD) fluorescence spectroscopy, we were able to find the behavior of the drug-concentration-dependent Langmuir-type principal component vectors. KSVD obtained by the Langmuir equation showed a high correlation with the static extinction constant V. Therefore, KSVD indicates the association constant of the drug with BSA and it was found that NPX and IBP had higher values than KP. Finally, in the analysis of the temperature factors of amino acid residues in each drug-binding region and Trp residues, KP and NPX significantly reduced these temperature factors whereas DZP and IBP hardly changed them. This result is consistent with the dynamic and static quenching dominance in the total quenching mechanism. Summarizing the results so far, it was shown that penetration into the hydrophobic core inside BSA can be achieved not only by one of the multiple aromatic rings and propionic acid groups but also by the joint effect of both. In this study, SVD enabled us to extract information on drug adsorption to BSA from fluorescence spectra. Furthermore, the application of SVD is expected to make it possible to perform fluorescence analysis for drug binding to proteins without being limited by the fluorescence properties of the drug.

Evaluation of the in vitro permeation parameters of topical ketoprofen and lidocaine hydrochloride from transdermal Pentravan® products through human skin.

In the treatment of pain, especially chronic pain, the rule of multimodal therapy applies, based on various painkillers mechanisms of action. The aim of the conducted study was to evaluate the in vitro penetration of ketoprofen (KET) and lidocaine hydrochloride (LH) through the human skin from a vehicle with transdermal properties. The results obtained with the use of the Franz chamber showed statistically significantly higher penetration of KET from the transdermal vehicle as compared to commercial preparations. It was also shown that the addition of LH to the transdermal vehicle did not change the amount of KET permeated. The study also compared the penetration of KET and LH by adding various excipients to the transdermal vehicle. Comparing the cumulative mass of KET that penetrated after the 24-h study, it was observed that the significantly highest permeation was found for the vehicle containing additionally Tinctura capsici, then for that containing camphor and ethanol, and the vehicle containing menthol and ethanol as compared to that containing Pentravan® alone. A similar tendency was observed in the case of LH, where the addition of Tinctura capsici, menthol and camphor led to a statistically significant higher penetration. Adding certain drugs such as KET and LH to Pentravan®, and substances such as menthol, camphor or capsaicin, can be an interesting alternative to administered enteral drugs especially in the group of patients with multiple diseases and polypragmasy.

Aerobic degradation of ketoprofen by marine consortia: Fenton-like reaction and degradation pathway

Ketoprofen (KTP) as a non-steroidal anti-inflammatory drug has been detected in coastal environment due to its wide usage. However, little information is available about the fate of KTP in marine environment. In the present study, the aerobic degradation of 20 mg L−1 KTP using the enriched marine consortia was investigated. Results showed that CA consortium cultured with casamino acids exhibited a higher KTP-degrading ability than those cultured with glucose, yeast extract and mixed vitamins. During CA consortium-mediated degradation of KTP, additional casamino acids resulted in the production of H2O2 and OH. Fe(III) could be also reduced to Fe(II) by CA consortium. This result indicated the occurrence of Fenton-like reaction. Further studies found that both biogenic Fenton-like reaction and enzyme-catalyzed reactions were involved in the initial hydroxylation reaction of KTP, then the subsequent mineralization of KTP was only performed via enzyme-catalyzed reactions. High-throughput sequencing analysis showed that Halomonas, Marinobacter, Owenweeksia and Oceanimonas were significantly enriched in CA consortium. As these genera contain amino acid oxidases, and the former two genera are capable of reducing Fe(III), it is assumed that these genera participated in biogenic Fenton-like reaction. The involvement of biogenic Fenton-like reaction provides a new insight into understanding the fate of KTP and other similar organic pollutants in marine environment containing amino acids and iron.

Effect of biosolids amendment on the fate and mobility of non-steroidal anti-inflammatory drugs (NSAIDs) in a field-based lysimeter cell study

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used globally to treat and prevent illness. Biosolids change physico-chemical characteristics of soil and can affect the mobility of NSAIDs. A field-based lysimeter study evaluated the effect of three rates (0, 7, and 28 Mg ha−1) of alkaline treated biosolids (ATB) on the leaching potential of naproxen (NPX), ibuprofen (IBF), and ketoprofen (KTF) over 34 days in a sandy loam textured soil. Although all three NSAIDs in the lysimeter cells vertically migrated to deeper soil depths after spiking, the sum of all NPX, IBF, and KTF detected in the leachate samples from all treatments were only 0.03%, 0.02%, and 0.04% of the initial spiking mass to the surface soil, respectively. A mass balance analysis indicated a low accumulation of these compounds in the soil at the end of the study (Day 34) from all treatments with only 4.8%, 0.5%, and 0.7% of initial spiked NPX, IBF, and KTF, respectively. Application of ATB significantly increased soil pH and organic matter (OM) content of the soils but did not impact retention of the compounds in the soil profile. Overall, all three NSAIDs in the present study presented low mobility in the loamy sand textured agricultural soil.

MIL-53 (Al) nanostructure for non-steroidal anti-inflammatory drug adsorption in wastewater treatment: Molecular simulation and experimental insights

Pharmaceuticals are prevalent in the environment, especially the nanostructures of non-steroidal anti-inflammatory drugs (NSAIDs) in water, which can harm human health and the environment. Adsorption processes are effective and energy efficient for removing contaminants. In this study, a new adsorbent, MIL-53 (Al), was used to remove pharmaceutical pollutants, including diclofenac (DIC), ketoprofen (KET), indomethacin (IND), and mefenamic acid (MFA), from wastewater. This study employed a combination of quantum mechanical (QM) calculations, Monte Carlo (MC) simulations, and molecular dynamics (MD) simulations to understand the adsorption behaviors of these contaminants. This study first analyzed the structures of the contaminants and the adsorbent using various techniques, such as electrostatic potential, reduced density gradients, and Hirshfeld surfaces. Then, we investigated the adsorption affinity of pharmaceutical pollutants on MIL-53 (Al) using the COSMO sigma profile and HOMO–LUMO energies. The simulation results revealed that HBs, electrostatic interactions, and π–π stacking primarily contribute to the adsorption mechanism. Laboratory tests confirmed the synthesis of MIL-53 using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and wide-angle X-ray diffraction (WAXD). Ultraviolet-visible (UV–Vis) spectroscopy was performed to analyze the adsorption of the targeted drugs, and the experimental results agreed well with the modeling results. This study concluded that MIL-53 (Al) has the potential to serve as an effective adsorbent for the removal of pharmaceutical pollutants from wastewater because of its strong adsorption properties.

Design and Development of Functionalized Single-walled Carbon Nanotube-ethosomes for Transdermal Delivery of Ketoprofen.

The purpose of this study was to combine carbon nanotube with ethosomes in order to obtain hybrid nanocarriers for transdermal delivery of ketoprofen (KP). KP-loaded functionalized single-walled carbon nanotube (f-SWCNTs) composite ethosomes (f-SWCNTs-KP-ES) were designed and were verified by a series of characterizations. The particle size of the preparation is less than 400 nm. DSC and XRD experiments showed that KP existed in an amorphous state after it was adsorbed and loaded on f-SWCNTs. TEM experiments showed that the structure of SWCNTs remained intact after oxidation and modification by PEI. FTIR results showed that PEI were successfully modified on the surface of SWCNT-COOH, and KP was successfully loaded on f-SWCNTs. In vitro release characteristics showed that the preparation had sustained release behavior and conformed to the first-order kinetic equation model. In addition, f-SWCNTs-KP-ES gel were prepared and in vitro skin permeation and in vivo pharmacokinetics were studied. The results showed that f-SWCNTs-KP-ES gel could enhance the skin permeation rate of KP and increase the drug retention of drugs in the skin. The characterization results consistently showed f-SWCNTs is a promising drug carrier. The hybrid nanocarrier prepared by the combination of f-SWCNTs and ethosomes can enhance the transdermal absorption of drugs and improve the bioavailability of drugs, which has a certain significance for the development of advanced hybrid nano-preparations.

Core-Shell Structured PLGA Particles Having Highly Controllable Ketoprofen Drug Release.

The non-steroid anti-inflammatory drug ketoprofen (KP) as a model molecule is encapsulated in different poly(lactide-co-glycolide) (PLGA) nanostructured particles, using Tween20 (TWEEN) and Pluronic F127 (PLUR) as stabilizers to demonstrate the design of a biocompatible colloidal carrier particles with highly controllable drug release feature. Based on TEM images the formation of well-defined core-shell structure is highly favorable using nanoprecipitation method. Stabile polymer-based colloids with ~200-210 nm hydrodynamic diameter can be formed by successful optimization of the KP concentration with the right choice of stabilizer. Encapsulation efficiency (EE%) of 14-18% can be achieved. We clearly confirmed that the molecular weight of the stabilizer thus its structure greatly controls the drug release from the PLGA carrier particles. It can be determined that ~20% and ~70% retention is available with the use of PLUR and TWEEN, respectively. This measurable difference can be explained by the fact that the non-ionic PLUR polymer provides a steric stabilization of the carrier particles in the form of a loose shell, while the adsorption of the non-ionic biocompatible TWEEN surfactant results in a more compact and well-ordered shell around the PLGA particles. In addition, the release property can be further tuned by decreasing the hydrophilicity of PLGA by changing the monomer ratio in the range of ~20-60% (PLUR) and 70-90% (TWEEN).

Selection and Evaluation of Model Pollutants for Performance Assessment of Advanced Treatment of Industrial Park Wastewater by Ozonation

Ozonation has gradually become a routine process for advanced wastewater treatment. During the technology innovation on the advanced treatment of wastewater by ozonation, researchers have to assess the performance of abundant new technologies, new reactors, and new materials. However, they are usually puzzled by the rational selection of model pollutants to assess the capability of such new technologies to eliminate the chemical oxygen demand (COD) and total organic carbon (TOC) of practical wastewater. It is unclear how well the various model pollutants reported in the literature could represent the COD/TOC removal of actual wastewater. The rational selection and evaluation of model pollutants for advanced treatment of industrial wastewater is of great significance in establishing the technological standard system for advanced treatment of wastewater via ozonation. Herein, the aqueous solutions (including unbuffered solutions and bicarbonate-buffered solutions) of 19 model pollutants and four practical secondary effluents from industrial parks were investigated through ozonation under identical conditions. The similarity in COD/TOC removal of the above wastewater/solutions were evaluated using mainly clustering analysis. The results showed that the dissimilarity among the model pollutants was greater than that among the actual wastewaters, thus enabling the rational selection of several model pollutants to assess the performance of advanced treatment of wastewater using ozonation by different technologies. The errors of predicting the COD removal of secondary sedimentation tank effluent by ozonation in 60 min using the unbuffered aqueous solutions of ketoprofen (KTP), dichlorophenoxyacetic acid (2,4-D), and sulfamethazine (SMT) were less than 9%, and those using the bicarbonate-buffered solutions of phenacetin (PNT), SMT, and sucralose were less than 5%. The evolution of pH by using the bicarbonate-buffered solutions was more similar to that in practical wastewater than by using unbuffered aqueous solutions. In the similarity evaluation of COD/TOC removal between the bicarbonate-buffered solutions and the practical wastewaters, the results were almost the same whether considering different input ozone concentration conditions. Therefore, the protocol proposed in this study based on similarity evaluation to assess the performance treating actual wastewater could be extended to different ozone concentration conditions with certain universality.

Influence of iontophoresis on delivery of NSAID-loaded deformable liposomal dispersions: in vitro and in vivo evaluation.

Aim: Negatively charged deformable liposomes (DL) of ketoprofen were formulated to enhance transdermal delivery of ketoprofen (KP) under the influence of iontophoresis for intraarticular delivery. Methods: Conventional and deformable KP liposomes were prepared using thin film hydration, characterized and intraarticular delivery of KP was evaluated using Sprague-Dawley rats. Results: Vesicles displayed entrapment efficiency (>71%); zeta potential <-25mV; size between 152.4±12.42nm to 220.4±6.22nm, KP-DL were stable under iontophoresis. Conventional and deformable liposomes exhibited relatively higher iontophoretic flux values than passive flux; Iontophoretic delivery enhanced KP availability in the synovial fluid (1.34±0.12μg.h/ml) fourfold over passive delivery (0.329±0.15μg.h/ml). Conclusion: Iontophoretic mediated transport of deformable liposomes could improve transdermal delivery of ketoprofen into the synovial joints than conventional liposomes.

Quantitative Analysis of Drug Supersaturation Region by Temperature-Variable Nuclear Magnetic Resonance Measurements, Part 2: Effects of Solubilizer

This study utilized temperature-variable nuclear magnetic resonance (NMR) spectroscopy to investigate the effects of a solubilizing agent on the ketoprofen (KTP) supersaturation region. Quantitative NMR analysis showed that the solubilizing agent cetyltrimethylammonium bromide (CTAB) increased both the crystalline and amorphous solubilities of KTP, shifting the KTP supersaturation region to a higher KTP concentration range. The amorphous solubility of KTP was found to be independent of the enantiomeric composition of KTP, even in the presence of CTAB. However, the supersaturation region of the S-enantiomer of KTP (s-KTP) in CTAB solutions was smaller than that of the racemic form of KTP (rac-KTP), likely because of the higher crystalline solubility of s-KTP. When KTP formed a KTP-rich phase via liquid-liquid phase separation from KTP-supersaturated solutions, CTAB was observed to be distributed into the KTP-rich phase, decreasing the chemical potential of KTP and the maximum thermodynamic activity of KTP in the aqueous phase. Additionally, the incorporation of CTAB into the KTP-rich phase diminished the solubilization effect of CTAB micelles in the aqueous phase, narrowing the KTP supersaturation region to a greater extent at higher KTP dose concentrations. Furthermore, the upper-temperature limit of the supersaturated dissolvable region of KTP was lowered in the presence of CTAB, which was rationalized by the melting point depression of the KTP crystal upon mixing with CTAB. The findings of this study highlight the importance of considering the molecular-level impact of solubilizing agents on the drug supersaturation region to fully exploit the potential benefits of supersaturated formulations.

Quantitative Analysis of Drug Supersaturation Region by Temperature-Variable Nuclear Magnetic Resonance Measurements, Part 1: Effects of Polymer and Drug Chiralities.

We examined the effects of the polymer-additive and drug chiralities on the ketoprofen (KTP) supersaturation region using temperature-variable nuclear magnetic resonance (NMR). Quantitative NMR analysis revealed that the racemic KTP and corresponding S-enantiomer (rac- and s-KTP) exhibited similar amorphous solubilities in a buffer, while the crystalline solubility of s-KTP was higher than that of rac-KTP. Therefore, rac-KTP exhibited a larger supersaturation region than s-KTP. In contrast, polyvinylpyrrolidone (PVP) reduced the amorphous solubility of both rac- and s-KTP, whereas the crystalline solubility of KTP remained unchanged. Partitioning PVP into the KTP-rich phase reduced the chemical potential of KTP in the KTP-rich phase and the amorphous solubility of KTP. At higher temperatures, the distribution of PVP into the KTP-rich phase became more significant, which considerably reduced the amorphous solubility. Because the upper limit of the KTP supersaturation decreased, PVP narrowed the KTP supersaturation region. The maximum KTP supersaturation ratio decreased with increasing temperature, and the supersaturated dissolvable area of KTP finally disappeared. The maximum temperature at which KTP can form the supersaturation was lowered by replacing rac- with s-KTP and the addition of PVP. The maximum supersaturation temperature was dominated by the melting behavior of crystalline KTP in an aqueous solution. The present study highlighted that a quantitative understanding of the supersaturation region is essential to determine whether supersaturated formulations are beneficial for improving the oral absorption of poorly water-soluble drugs.

LC-MS/MS approach for simultaneous assessment of hyoscine N-butyl bromide and ketoprofen in biological fluids and pharmaceuticals.

The mixture of hyoscine N-butyl bromide (HBB) and ketoprofen (KTP) is commonly used for the handling of abdominal spasms and pain relief. There are two challenges that restrict the simultaneous assessment of HBB and KTP in biological fluids and pharmaceuticals. The first issue is the difficulty of elution of HBB and the second one is the presence of KTP as a racemic mixture in all pharmaceutical formulations, which obscures its appearance as a single peak. An ultrasensitive and highly efficient liquid chromatography-mass/mass spectrometric (LC-MS/MS) method is designed and validated for the first concurrent assessment of HBB and KTP in spiked human serum and urine, and pharmaceutical formulations. The estimated linearity ranges for HBB and KTP were respectively, 0.5-500 and 0.05-500 ng/ml, with excellent correlation coefficients. Validation results showed that the value of relative standard deviations were <2% for HBB and KTP. The mean extraction recoveries for HBB and KTP were, respectively, 91.04 and 97.83% in Spasmofen® ampoules; 95.89 and 97.00% in spiked serum; and 97.31 and 95.63% in spiked urine. The presented innovative chromatographic approach was utilized for the measurement of trace amounts of coexisting pharmaceuticals in pharmacokinetics studies and routine therapeutic medication monitoring.

Detection of Carbamazepine, Diclofenac, and Ketoprofen via a SPE-HPLC-PDA Method in a Municipal Wastewater Treatment Plant in East Texas, USA

Increased demand for water reuse, recycling and reclamation heightens the need for improvements in the design of wastewater treatment plants that minimize or remove toxic pollutants or their metabolites. In this study, solid-phase extraction (SPE) technique utilizing C-18 cartridge was used for separation of three commonly used pharmaceuticals, namely, carbamazepine (CBZ), diclofenac (DF), and ketoprofen (KT) in wastewater samples. High performance liquid chromatography-photodiode array detector (HPLC-PDA) method was used for detection of CBZ, DF, and KT along the treatment stages (aeration, clarifier, raw activated sludge (RAS), chlorine contact chamber (CCC), and sulfur dioxide chamber) from Nacogdoches wastewater treatment plant (NWWTP), in East Texas, USA. Highest concentrations were found in the RAS followed by influent aeration stage. Pharmaceutical concentrations detected from the influent or RAS samples were 2.115 × 10−3 mg/L, 8.95 × 10−4 mg/L and 8.55 × 10−4 mg/L for CBZ, KT and DF, respectively. Highest detected total concentrations of pharmaceuticals were: carbamazepine (1.285 – 2.117 μg/L), diclofenac (0.600 – 0.865 μg/L), and ketoprofen (0.815 – 0.885 μg/L). The calculated % removal efficiencies along the treatment stages follow the order; CBZ: RAS > SO2 > clarifier ≈ aeration > CCC; KT: RAS > SO2 > aeration > CCC > clarifier; DF: RAS ≈ aeration ≈ CCC > clarifier > SO2. Determined removal efficiencies follow the order carbamazepine (∼ 39.2%) > diclofenac (∼ 30.6%) > ketoprofen (∼8.8%). Removal efficiencies of pharmaceuticals in the NWWTP may be affected by the human body, transition through activated wastewater treatment processes, and their metabolism and/or usage by humans.

Combining Constructed Wetlands and UV Photolysis for the Advanced Removal of Organic Matter, Nitrogen, and Emerging Pollutants from Wastewater

This study reports the performance of a three-step lab-scale system including a hybrid digester (HD), a vertical flow (VF) constructed wetland, and a photodegradation (PD) lamp, with two different arrangements regarding the position of the recirculation point. In addition to total suspended solids (TSS), chemical oxygen demand (COD), and nitrogen compounds, removal of the following pollutants was investigated: paracetamol (ACE), ofloxacin (OFL), caffeine (CAF), ketoprofen (KET), ibuprofen (IBU), clofibric acid (ACB), bisphenol A (BPA), and sotalol (SOT). An excellent performance of HD was achieved on the elimination of TSS (82.2 ± 18.5% on average) and COD (63.9 ± 4.1%). TSS and COD removal increased to 91.2 ± 0.4% and 83.4 ± 2.9%, respectively, for the combined HD–VF system. Ammonia removal was 57.0 ± 7.8% in the VF unit while significant denitrification occurred in the HD. The overall HD–VF–PD system achieved mean removals of 100% for OFL, KET, SOT, and IBU, 98 ± 2% for ACE, 87 ± 8% for CAF, 81 ± 38% for ACB and 26 ± 9% for BPA. The removal of ACE, OFL, CAF, and IBU was mostly by biodegradation in the HD and VF units while the PD unit was responsible for the removal of KET, ACB, and SOT.

Removal of Contaminants of Emerging Concern from Wastewater Using an Integrated Column System Containing Zero Valent Iron Nanoparticles

Non-steroidal anti-inflammatory drugs (NSAIDs) and endocrine disruptors (EDCs) are among the most important categories of contaminants of emerging concern (CECs), and many advanced technologies have been developed for their elimination from water and wastewater, including nano-zero valent iron (nZVI). This study investigates the performance of nZVI synthesized from green tea extracts and incorporated into a cationic resin (R-nFe) in the removal of four selected NSAIDs, namely ibuprofen (IBU), naproxen (NPX), diclofenac (DCF), and ketoprofen (KFN), and an EDC, namely bisphenol A (BPA). Column experiments were conducted to evaluate the effect of various operating parameters, including initial CECs concentration, contact time, pH, addition, and dose of sodium persulfate (PS). To the authors’ knowledge, this is the first time that environmentally friendly produced nZVI has been combined with PS in column experiments for the removal of CECs from wastewater. With a contact time of 2.2 min, PS = 1 mM, and influent pH = 3.5, 27–72% of IBU, 70–99% of NPX, 70–95% of DCF, 28–50% of KFN, and 61–91% of BPA were removed during a 12-day operation of the system, while the initial concentration of each substance was 5 μg/L. Therefore, it is anticipated that the proposed system could be a promising post-treatment technology for the removal of CECs from wastewater.

Ibuprofen and Ketoprofen—Inert Drugs or Potential Environmental Hazard?

Ibuprofen (IBU) and ketoprofen (KET) are among the world’s most popular and widely used nonsteroidal anti-inflammatory drugs (NSAIDs). Due to their high usage, these drugs have entered the environment, including the soil, and, like any other chemical compound, can have a negative effect on it. Therefore, an attempt was made to evaluate the effects of these two popular drugs on soil bacteria and fungi, the bivalve crustaceans (Heterocipris incongruens) and the growth and development of spring barley. The tested drugs did not show any negative effects on the total bacterial abundance. Effects were observed on the growth and survival of H. incongruens and on the abundance of fungi in the soil at the highest concentrations tested. The presence of IBU and KET in the soil in which spring barley was cultivated caused an increase in the activity of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and guaiacol peroxidase (POD); an increase in the content of proline and ascorbic acid (AsA) in the seedlings of this grain; and a decrease in the yield of fresh plant weight, especially at the application of concentrations of 100 and 1000 mg·kg−1 of soil’s dry weight (DW). Effects on barley seed germination potential and germination capacity, plant dry matter content, assimilation pigment content and malondialdehyde (MDA) were also observed at the highest concentrations.

The regulation of electron distribution on Fe Lewis acidic sites within silicon skeleton and its contribution to Ketoprofen ozonation

Lewis acid site was vital center for activating O3 during catalytic ozonation process. Herein, we proposed a strategy to enhance the Lewis acid strength of Fe-MCM-48 (FeM) by fluorination. Fluorinated Fe-MCM-48 (FFeM) exhibited the better catalytic ozonation efficiency towards Ketoprofen (KET), a kind of nonsteroidal anti-inflammatory drug. 87.4 % TOC removal was obtained by F2.5Fe0.8M/O3 process, but only 27.5 % and 52.7 % were found by sole ozonation and Fe0.8M/O3 processes, respectively. Comparative characterizations, experiments and DFT calculations showed that fluorinated FFeM was regular sphere with three dimensional duct channel and large SBET. Doping of F reduced particle size, implanted electron withdrawing Si-F group and formed the electron poor center around Fe atom, which enhanced Lewis acid strength of FFeM. Protonated hydroxyl groups on Lewis acid sites were the main active sites for O3 activation. Greater amount of O3 were absorbed on the surface of FFeM and the greater O3 utilization rate, •OH and •O2– generation rates were obtained by FFeM/O3 process. Common anions such as Cl−, SO42− and NO3– and Humic acids (HA) had little effect on KET removal but inhibited TOC removal in FFeM/O3 process. •OH, •O2– and Fe(IV) = O oxidation were accounted for KET degradation. 16 kinds of intermediates generated from KET degradation and 4 pathways were deduced.

Spectrochemical, medicinal, and toxicological studies of ketoprofen and its newly designed analogs; quantum chemical, and drug discovery approach

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as analgesics, antipyretics, anti-clotting, and anti-inflammatory agents. One such NSAID, ketoprofen (KTP), is prescribed to treat pain, sprains, menstrual irregularities, osteoarthritis (OA), and rheumatoid arthritis (RA). By inhibiting cyclooxygenase, it halts prostaglandin synthesis. However, it exhibits significant side effects in humans and other living things. Herein, the chemical structure of KTP has been modified to search for improved chemical and medicinal effects. Density functional theory (DFT) has been employed for geometry optimization. Molecular docking and molecular dynamics (MD) simulations were conducted to investigate the binding affinity and stability of the protein-drug complex with prostaglandin synthase protein. ADMET predictions were carried out to calculate and compare the pharmacokinetic behavior of KTP and its new analogs. Spectral and chemical results support the structural conformation of the new analogs, all of which exhibit improved physicochemical, and binding properties compared to the parent drug. After a 100 ns MD simulation, the drugs remained tightly bound to the binding site of the receptor protein, showing significant interactions with shorter distances among the new analogs. The ADMET predictions confirmed better pharmacokinetic properties of novel analogs compared to KTP. The study compares several KTP metabolites using thermo-chemical, spectral, biological, and toxicological analysis. Results showed the reactivity and stability, with spectral data evaluating all KTP analogs. ADMET predicts that all KTP derivatives are less toxic and have better pharmacokinetic features than KTP. Most KTP analogs exhibit excellent oral bioavailability and significant analgesic, antipyretic, and anti-inflammatory functions. These findings support the potential use of these drugs in the future drugs.

Investigating the physicochemical properties of solid dispersions based on semicrystalline carriers: A case study with ketoprofen

Hydrophilic semicrystalline carriers represent an alternative to amorphous polymers due to their low melting temperature, useful for the production of solid dispersions (SDs) by melting-based technologies. This research aims to compare SDs of ketoprofen (KET) and three different semicrystalline carriers (PEG, Poloxamer and Gelucire) regarding miscibility, phase behavior, molecular interactions and stability. KET was chosen owing to its low solubility and high glass forming ability. Estimation of drug-excipient miscibility was performed by Flory-Huggins theory. Negative Gibbs free energy indicated a spontaneous mixing of KET with the three carriers and miscibility in the order PEG > Poloxamer > Gelucire. SDs up to 40 % w/w of drug were produced by melting process at a temperature below KET melting point. Characterization of SDs was performed by differential scanning calorimetry, polarized light microscopy and powder X-ray diffraction. In case of PEG and Poloxamer, the drug incorporation did not affect carrier crystallinity, while KET was in the amorphous state. Differently, KET retarded the crystallization of Gelucire and at high drug loadings the SDs were amorphous and semisolid. FT-IR analysis revealed a strong interaction between KET and the three carriers. Finally, PEG-based SDs above 20 % KET loading displayed drug crystallization after 6 months of storage; while Poloxamer and Gelucire-based SDs showed KET crystallization only at 40 % KET. Due to its less hydrophilic character and limited water uptake, Gelucire showed the best stability among the three excipients.