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Caprine tuberculosis (TB) is a zoonosis caused by members of the Mycobacterium tuberculosis complex (MTBC). Caprine TB eradication programmes are based mainly on intradermal tuberculin tests and slaughterhouse surveillance. Different factors may affect the performance of the TB diagnostic tests used in caprine herds and, therefore, their ability to detect infected animals. The present study evaluates the effect of the fraudulent administration of two anti-inflammatory substances, dexamethasone and ketoprofen, on the performance of the TB diagnostic techniques used in goats, as well as the suitability of high performance liquid chromatography (HPLC) for their detection in hair samples. The animals (n = 90) were distributed in three groups: (1) a group treated with dexamethasone (n = 30); a second group treated with ketoprofen (n = 30); and a third non-treated control group (n = 30). Both dexamethasone and ketoprofen groups were subjected to intramuscular inoculation with the substances 48 h after the administration of bovine and avian purified protein derivatives (PPDs), that is, 24 h before the tests were interpreted. All the animals were subjected to the single and comparative intradermal tuberculin (SIT and CIT, respectively) tests, interferon-gamma release assay (IGRA) and P22 ELISA. The number of SIT test reactors was significantly lower in the dexamethasone (p = 0.001) and ketoprofen (p < 0.001) groups 72 h after the bovine PPD inoculation compared with the control group. A significantly higher number of positive reactors to IGRA was detected within the dexamethasone group (p = 0.016) 72 h after PPD administration compared to the control group. Dexamethasone and ketoprofen detection in either hair or serum samples was challenging when using HPLC since these substances were not detected in animals whose skin fold thickness (SFT) was reduced, what could be an issue if they are used for fraudulent purposes. In conclusion, the parenteral administration of dexamethasone or ketoprofen 48 h after the PPDs administration can significantly reduce the increase in SFT (mm) and subsequently the number of positive reactors to SIT test.

Due to the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs), the incidence of NSAID-associated adverse events has increased exponentially over the past decades. Ketoprofen (ketoprofen acid, KA) is a widely used NSAID and, like with other NSAIDs, its use can be associated with adverse effects that especially involve the gastrointestinal tract and the kidney. The salification of KA with L-lysine has led to the synthesis of ketoprofen lysine salt (KLS), which is characterized by higher solubility and a more rapid gastrointestinal absorption compared to KA. Previous studies have reported that KLS has also an increased gastric tolerance in vitro, and this is due to the inhibition of lipid peroxidation and reactive oxygen species scavenging effects of L-lysine. Here, we report in vivo tolerability/toxicity studies that were conducted prior seeking KLS marketing authorization, in which we compared KLS and KA safety profile, focusing in particular on the evaluation of the gastrointestinal and renal tolerability of the drugs administered orally to dogs. Our results demonstrate that KLS has an increased in vivo gastrointestinal tolerability compared to KA and show, for the first time, that KLS has also increased in vivo renal tolerability compared to KA, thus supporting the concept that L-lysine may counteract NSAID-induced oxidative stress-mediated gastrointestinal and renal injury.

Clinical trials of new drugs often face a high failure rate of approximately 45 percent due to safety and toxicity concerns. Repurposing drugs with well-established safety profiles becomes crucial in addressing this challenge. Colon cancer ranks as the third most prevalent cancer and the second leading cause of cancer related mortality worldwide. This study focuses on the RNA-binding protein pumilio1 (PUM1), a member of the PUF family involved in post-transcriptional gene expression regulation. By utilizing molecular docking techniques and FDA-approved drugs, potential inhibitors against PUM1 were identified. Notably, dolasetron and ketoprofen demonstrated promising results, exhibiting strong binding affinity, hydrophobic interactions, and favorable chemical reactivity according to Conceptual-DFT calculations. Both compounds effectively reduced cell viability, with IC50 values of 150 µM and 175 µM, respectively and shows long term inhibitory effects as seen by reduced in number of colonies. Moreover, they exhibited inhibitory effects on colon cancer stem cells, as indicated by reduced colonospheroid size and numbers. Apoptosis is induced by these compounds and has triggered activation of executioner caspase 3/7 in HCT116 cells which is evident through a caspase 3/7 assay and AO/EB staining, while the non-toxic effect of these compounds was evident from viability against non-cancerous cell line and hemolysis assay. Additionally, the treatment group showed a significant decrease in PUM1 and cancer stem cell markers expression compared to the control group. In conclusion, this study highlights the potential of targeting PUM1 as a novel approach to colon cancer treatment. Dolasetron and ketoprofen demonstrate promise as effective anti-cancer and anti-cancer stem cell drugs, inducing apoptosis in colon cancer cells through inhibition of PUM1.

HCC is a highly aggressive malignancy with limited treatment options. In this study, novel conjugates of non-steroidal anti-inflammatory drugs (NSAIDs)—Ibuprofen and Ketoprofen—with oleanolic acid oximes derivatives (OAO) were synthesized, and their activity as modulators of signaling pathways involved in HCC pathogenesis was evaluated in normal THLE-2 liver cells, and HCC-derived HepG2 cells. The results demonstrated that conjugation with OAO derivatives reduces the cytotoxicity of parent compounds in both cell lines. In THLE-2 cells, treatment with conjugates resulted in increased activation of the Nrf2-ARE pathway. An opposite effect was observed in HepG2 cells. In the later reduction of NF-κB, it was observed along with modulation of MAPK signaling pathways (AKT, ERK, p38, p70S6K, and JNK). Moreover, STAT3, STAT5, and CREB transcription factors on protein levels were significantly reduced as a result of treatment with IBU- and KET-OAO derivatives conjugates. The most active were conjugates with OAO-morpholide. Overall, the findings of this study demonstrate that IBU-OAO and KET-OAO derivative conjugates modulate the key signaling pathways involved in hepatic cancer development. Their effect on specific signaling pathways varied depending on the structure of the conjugate. Since the conjugation of IBU and KET with OAO derivatives reduced their cytotoxicity, the conjugates may be considered good candidates for the prevention of liver cancer.

Two spectrometric methods and a TLC-densitometric method are described for the determination of hyoscine/ketoprofen combination. A new spectrophotometric method called the co-absorptive point has been explained based on the idea of the isosbestic point. This method has been introduced to resolve the overlapped spectra and the challenging drug ratios found in the mentioned dosage form. Also, a dual wavelength technique measuring at 208.4 and 218.2 nm was explained. In the two spectrometric techniques, ketoprofen was determined by zero-order spectra, while hyoscine was determined by co-absorptive point and dual wavelength techniques with linearity ranges of 8–100 and 8–70 µg/mL. In the TLC-densitometric method, the developing phase was methanol-ethyl acetate-ammonia (35 : 65 : 5, v/v) with linearity ranges of 1–20 and 5–25 µg/mL for hyoscine and ketoprofen, respectively. The greenness of the described techniques was assessed according to the eco-scale and compared to previously reported methods. [ABSTRACT FROM AUTHOR]

Binder jetting has the potential to revolutionize the way we produce medicine. However, tablets produced by binder jetting technology can be quite fragile and hard to handle. In this study, the printing process and ink composition were examined to optimize the mechanical properties of tablets. A model formulation containing the ketoprofen drug was developed and used as a base for optimization. Firstly, important printing parameters were identified with a fractional factorial design. Saturation and layer height critically influenced selected tablet properties. Relevant process parameters were optimized for tablet mechanical strength by using the D-optimization DoE approach. The best mechanical properties were achieved when saturation was set to 1 and layer height to 150 µm. On the other hand, binder ink composition did not appear to impact tablet mechanical strength as much as process parameters did. Three ethanol-water mixtures were tested at three tablet strength levels and no definitive conclusions could be drawn. The binder jetting process can be wasteful, especially if the unbound powder cannot be reused. To determine the suitability of powder blend recycling, the ketoprofen content was measured for 27 subsequent batches of tablets. While the trendline did indicate a slight reduction in ketoprofen content, the powder blend reuse can nevertheless be employed. [ABSTRACT FROM AUTHOR]

A new series of the anti-inflammatory drug ketoprofen derivatives bearing aryl chalcone-amide congeners were synthesized. The structures of the synthesized compounds were identified by the 1H NMR, 13C NMR, and EIMS spectroscopic methods. The inhibitory activity of the synthesized compounds on cholinesterase enzymes was investigated. Biological results revealed that five compounds displayed moderate activities against acetylcholinesterase (AChE) with IC50 values below 10 μM. Among the tested compounds, (BTPhP) was found to be the most potent against AChE (IC50 0.98 ± 0.02 μM), while the chalcone-amide analogues (MeOPh), (HydPh), (FPh), and (ChPh) exhibited moderate activities with IC50 values ranged between 5.19–9.61 μM. Molecular docking study showed that compound (BTPhP) could combine with the active site of acetylcholinesterase by the π–π between the ketoprofen phenyl groups is embedded in a cavity surrounded by two aromatic residues of Tyr334 and Trp279. The present results strongly suggest that the para-position of the D-ring should be a preferred modification site for further structural optimization design. Thus, compound (BTPhP) emerged as a promising lead for the development of new acetylcholinesterase inhibitor agent. The preliminary quantum structure-activity relationship (QSAR) among the newly synthesized congeners was obtained by Genetic Function Approximation (GFA). [ABSTRACT FROM AUTHOR]

In this study, lipase from Aspergillus niger immobilized by physical immobilization by the adsorption interactions and partially interfacial activation and mixed physical immobilization via interfacial activation and ion exchange was used in the kinetic resolution of the ketoprofen racemic mixture. The FTIR spectra of samples after immobilization of enzyme-characteristic signals can be seen, and an increase in particle size diameters upon immobilization is observed, indicating efficient immobilization. The immobilization yield was on the level of 93% and 86% for immobilization unmodified and modified support, respectively, whereas activity recovery reached around 90% for both systems. The highest activity of immobilized biocatalysts was observed at pH 7 and temperature 40 °C and pH 8 and 20 °C for lipase immobilized by physical immobilization by the adsorption interactions and partially interfacial activation and mixed physical immobilization via interfacial activation and ion exchange, respectively. It was also shown that over a wide range of pH (from 7 to 10) and temperature (from 20 to 60 °C) both immobilized lipases retained over 80% of their relative activity, indicating improvement of enzyme stability. The best solvent during kinetic resolution of enantiomers was found to be phosphate buffer at pH 7, which obtained the highest efficiency of racemic ketoprofen methyl ester resolution at the level of over 51%, followed by enantiomeric excess 99.85% in the presence of biocatalyst obtained by physical immobilization by the adsorption interactions and partially interfacial activation. [ABSTRACT FROM AUTHOR]

In this study, we report for the first time application of magnetic ionic liquid (MIL), (Z)-octadec-9-en-1-aminium tetrachloroferrate (III) in the simultaneous preconcentration and quantification of 3 different categories of pharmaceutical products clomipramine, ketoprofen and loperamide from wastewater and human urine samples using dispersive micro-solid phase extraction detected and quantified in high-performance liquid chromatography with a diode-array detector. The MIL was characterized by magnetic property measurement systems, Fourier-transform infrared spectroscopy, zeta potential, nuclear magnetic resonance, Raman scattering spectroscopy, scanning electron microscopy and thermogravimetric analysis. First, a specified amount of the sorbent was successfully added to the sample solution containing the analytes. Afterward, the sample pH is adjusted and stirred at a constant rate of 700 rpm for 45 min. After the adsorption of the analytes, the sample is then sonicated for desorption then centrifuged and decanted for analysis. After optimization, the limit of detection (LOD) was within 2.3–2.9 μg/L and the linearity range was within 1–750 μg/L for all the analytes. The correlation coefficients (R2) obtained were in the range of 0.9967–0.9974, and the relative standard deviation (RSD, %) for intra-day and inter-day was within 2.7–3.3 and 2.6–3.7, respectively. Finally, the applicability of the method on real wastewater and human urine samples was examined and the preconcentration and quantification of the drugs at microgram levels were confirmed with satisfactory results. [ABSTRACT FROM AUTHOR]

A facile and efficient detection method is required to address the potential health risks of ketoprofen (KP) in animal-derived foods. Herein, we integrated molecularly imprinted polymers (MIPs) with Cu-doped Fe 3 O 4 nanozymes (Fe 3 O 4 –Cu) to develop a selective colorimetric sensor for KP detection. Chitosan and glutaraldehyde were used as functional monomers and cross-linkers to fabricate proposed the MIPs@Fe 3 O 4 –Cu. On KP addition, it was specifically captured by the imprinted cavities, thereby blocking the channels between chromogenic substrates and Fe 3 O 4 –Cu. Based on this rationale, a selective colorimetric sensor utilizing MIPs@Fe 3 O 4 –Cu was established, exhibiting a linear range of 0.25–100 μM and a detection limit of 0.073 μM. The developed method was validated through its application in milk samples, yielding satisfactory recoveries with low relative standard deviations. This efficient and selective colorimetric sensor holds immense significance for KP detection in complex samples. [Display omitted] • A selective colorimetric sensor for ketoprofen was constructed using MIPs@Fe 3 O 4 -Cu. • MIPs@Fe 3 O 4 -Cu achieved enhanced sensitivity and selectivity towards ketoprofen. • The strategy broadens a scope of the application of colorimetric methods. [ABSTRACT FROM AUTHOR]

[Display omitted] • In the early steps on ketoprofen photocatalysis a decarboxylation takes place. • IR and NMR studies indicate ketoprofen photocatalytic degradation into aromatics. • HPLC analysis indicates ketoprofen is degradated by several pathways. • The total mechanism for ketoprofen degradation are presented. • Ketoprofen TiO 2 photocatalytic degradation induces a mineralization of 70 %. Ketoprofen KET and other non-steroidal anti-inflammatory drugs NSAIDs are extensively used throughout the world to reduce pain, fever, and inflammation. As a result of this, they have been detected in environmental waters and represent a potential health risk. There are several reports about KET photocatalytic degradation but most of them deal with experimental conditions or catalytic materials to perform this process. In this study, the mechanisms and intermediates involved in KET photocatalysis with TiO 2 in aqueous media were investigated. First, the mineralization rate was assessed by TOC measurements. The formation and eventual degradation of intermediate organic compounds were investigated by HPLC, UV–Vis, IR, 1H NMR and HPLC-MS studies. TOC analysis indicate that KET is quickly transformed into other compounds that eventually are degradated and 70 % mineralization was achieved after five hours of irradiation. UV–Vis and HPLC studies indicate that KET is transformed into some other aromatic compounds within minutes. IR studies demonstrate the conversion of KET into several aromatic compounds which in turn degradate into low molecular saturated and unsaturated acids. 1H NMR studies indicate KET is transformed into several aromatic compounds such as 3-hydroxy-benzophenone, phenol, 1,4-hydroquinone, 1,2,4-benzenetriol, and catechol. HPLC-MS studies indicate KET is degradated by several photochemical and photocatalytic parallel mechanisms. Based on this and previous studies, a unified and complete mechanism for KET photocatalytic degradation is presented. [ABSTRACT FROM AUTHOR]

Objectives. The aim of this study was to investigate the influence of formulation factors on in vitro release of ketoprofen from sustained release inert matrix tablets. Materials and methods. Laboratory scale, Ketoprofen sustained release inert matrix tablets were manufactured using Kollidon® SR as matrix formator, by direct tableting of powder blends. The influence of the formulation factors (X1 – matrix formator excipient and X2 – diluent type) on in vitro release of ketoprofen from sustained release tablets was studied by using a full factorial 23 experimental plan. Outcomes. Pharmacotechnical characterization of manufactured laboratory scale batches was performed and all 12 batches fulfilled European Pharmacopeia requests. In vitro release showed a sustained release profile in all cases. Variance analysis (ANOVA) showed a good correlation between experimental conditions and answers. In vitro release testing was performed in phosphate buffer pH = 7.4. Percentage release was determined spectrophotometrically at 258 nm. A decrease in the rate of in vitro release was registered, up to 4 h and 6 h when lactose DC and mannitol DC were used as diluents, respectively. Isomalt DC has increased the rate of in vitro release up to 6 h. Conclusions. In vitro release data, corresponding to formulation N1 shoed a good fitting with Weitbull, KorshmeyerPeppas and Higuchi models while in vitro release data corresponding to formulation N8 presented a good fitting with Weitbull and Korsmeyer-Peppas. In case of formulations N1 and N8 a non-Fickian diffusion mechanism seems to be involved in drug release from the matrix tablets.

Wood decay fungi (WDF) are a well-known source of enzymes and metabolites which have applications in numerous fields, including myco-remediation. Pharmaceuticals are becoming more problematic as environmental water pollutants due to their widespread use. In this study, Bjerkandera adusta, Ganoderma resinaceum, Perenniporia fraxinea, Perenniporia meridionalis and Trametes gibbosa were chosen from WDF strains maintained in MicUNIPV (the fungal research collection of the University of Pavia) to test their potential to degrade pharmaceuticals. The degradation potential was tested in spiked culture medium on diclofenac, paracetamol and ketoprofen, three of the most common pharmaceuticals, and irbesartan, a particularly difficult molecule to degrade. G. resinaceum and P. fraxinea were found to be the most effective at degradation, achieving 38% and 52% (24 h) and 72% and 49% (7 d) degradations of diclofenac, 25% and 73% (24 h) and 100% (7 d) degradations of paracetamol and 19% and 31% (24 h) and 64% and 67% (7 d) degradations of ketoprofen, respectively. Irbesartan was not affected by fungal activity. The two most active fungi, G. resinaceum and P. fraxinea, were tested in a second experiment in discharge wastewater collected from two different wastewater treatment plants in northern Italy. A high degradation was found in azithromycin, clarithromycin and sulfametoxazole (from 70% up to 100% in 7 days).

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).

Solid dispersions are typically binary systems with a hydrophilic matrix polymer and a lipophilic active substance. During formulation, the drug undergoes a crystalline to amorphous phase transition, which leads to a supersaturated solution providing enhanced bioavailability. The interaction of the active substance and the polymer is unique and influences the level of supersaturation. We aimed to investigate the relationship between low molecular weight polyethylene glycol derivates PEG 1000, 1500, and 2000 and ketoprofen regarding the effect of molecular weight. The physicochemical properties of solid dispersions prepared with hot melt homogenization and their respective physical mixtures were investigated with Fourier transform infrared spectroscopy, powder X-ray diffraction and scanning electron microscopy techniques. A phase solubility study was carried out in hydrochloric acid media which showed no difference between the three polymers, but the dissolution curves differed considerably. PEG 1000 had higher percentage of released drug than PEG 1500 and 2000, which had similar results. These results indicate that when multiple low molecular weight PEGs are suitable as matrix polymers of solid dispersions, the molecular weight has only limited impact on physicochemical characteristics and interactions and further investigation is needed to select the most applicable candidate.

Current limitations of wound dressings for treating chronic wounds require the development of novel approaches. One of these is the immune-centered approach, which aims to restore the pro-regenerative and anti-inflammatory properties of macrophages. Under inflammatory conditions, ketoprofen nanoparticles (KT NPs) can reduce pro-inflammatory markers of macrophages and increase anti-inflammatory cytokines. To assess their suitability as part of wound dressings, these NPs were combined with hyaluronan (HA)/collagen-based hydro- (HGs) and cryogels (CGs). Different HA and NP concentrations and loading techniques for NP incorporation were used. The NP release, gel morphology, and mechanical properties were studied. Generally, colonialization of the gels with macrophages resulted in high cell viability and proliferation. Furthermore, direct contact of the NPs to the cells reduced the level of nitric oxide (NO). The formation of multinucleated cells on the gels was low and further decreased by the NPs. For the HGs that produced the highest reduction in NO, extended ELISA studies showed reduced levels of the pro-inflammatory markers PGE2, IL-12 p40, TNF-α, and IL-6. Thus, HA/collagen-based gels containing KT NPs may represent a novel therapeutic approach for treating chronic wounds. Whether effects observed in vitro translate into a favorable profile on skin regeneration in vivo will require rigorous testing.

Ketoprofen is an anti-inflammatory agent that may cause gastric irritation if administered orally. Dissolving microneedles (DMN) can be a promising strategy to overcome this issue. However, ketoprofen has a low solubility; therefore, it is essential to enhance its solubility using certain methods, namely nanosuspension (NS) and co-grinding (CG). This research aimed to formulate DMN containing ketoprofen-loaded NS and CG. Ketoprofen NS was formulated with poly(vinyl alcohol) (PVA) at concentrations of 0.5%, 1%, and 2%. CG was prepared by grinding ketoprofen with PVA or poly(vinyl pyrrolidone) (PVP) at different drug–polymer ratios. The manufactured ketoprofen-loaded NS and CG were evaluated in terms of their dissolution profile. The most promising formulation from each system was then formulated into microneedles (MNs). The fabricated MNs were assessed in terms of their physical and chemical properties. An in vitro permeation study using Franz diffusion cells was also carried out. The most promising MN-NS and MN-CG formulations were F4-MN-NS (PVA 5%-PVP 10%), F5-MN-NS (PVA 5%-PVP 15%), F8-MN-CG (PVA 5%-PVP 15%), and F11-MN-CG (PVA 7.5%-PVP 15%), respectively. The cumulative amounts of drug permeated after 24 h for F5-MN-NS and F11-MN-CG were 3.88 ± 0.46 µg and 8.73 ± 1.40 µg, respectively. In conclusion, the combination of DMN with nanosuspension or a co-grinding system may be a promising strategy for delivering ketoprofen transdermally.

Nowadays, ibuprofen and ketoprofen are widely used over-the-counter medications to treat inflammation, fever, or pain. Their high consumption and improper disposal cause them to get into the environment and often pollute surface water. In this study, the new polymeric porous microspheres based on 4-vinylpyridine (4VP) are presented as effective sorbents for ibuprofen and ketoprofen preconcentration and removal. The porous microspheres were obtained via seed swelling polymerization with the use of two types of methacrylate crosslinkers, i.e., trimethylolpropane trimethacrylate (TRIM) and 1,4-dimethacryloiloxybenzene (14DMB). Additionally, as a reference sorbent, a copolymer of styrene and divinylbenzene was obtained. Porous structure investigations showed that the microspheres possess a specific surface area of about 100 m2/g, but noticeable differences were observed in their internal topography depending on the type of crosslinker used. Moreover, the porous structure of dry and swollen microspheres differs significantly. Swollen copolymers reveal the presence of micropores. The 4VP microspheres are characterized by high thermal stability; their initial decomposition temperature is about 300 °C. The performance of the 4VP copolymers as sorbents in aqueous solutions of drugs was evaluated in static and dynamic modes at three pH values of 3, 7, and 11. The highest sorption efficiency was obtained for ibuprofen and ketoprofen in pH 3. Both 4VP copolymers indicate the high sorption capacity in a static sorption as follows: towards ketoprofen of about 40 mg/g whereas towards ibuprofen of about 90 mg/g and 75 mg/g on copolymer crosslinked with trimethylolpropane trimethacrylate and 1,4-dimethacryloiloxybenzene, respectively. The recovery of ibuprofen and ketoprofen after dynamic sorption experiments was higher than 90%. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the analgesic activity and acute toxicity of the ketoprofennicotinamide multicomponent solid. The preparation of multicomponent solids was carried out by the solvent evaporation method. The characterization of multicomponent solids was carried out by powder x-ray diffractometer (PXRD), differential scanning calorimeter (DSC), and fourier transform infrared spectrometer (FTIR). Solubility test was carried out by shaking method and evaluation of analgesic activity-toxicity was carried out in vivo in mice strain BALB/c. The results showed that the ketoprofen-nicotinamide multicomponent solid formed a new solid phase with different characteristics from the initial components. The ketoprofen-nicotinamide multicomponent solid showed a significantly (p<0.05) increased solubility, which was 1.3 times compared to the solubility of pure ketoprofen. In the evaluation of analgesic activity, the treatment group of multicomponent solid at a dose of 3.25 mg/kg body weight showed significantly increased pain inhibition (p<0.05) compared to the treatment group of pure ketoprofen. The toxicity evaluation in experimental animals showed that the multicomponent solids did not cause a significant (p>0.05) increase in SGOT and SGPT levels compared to the control group. Observations on the stomach histology of experimental animals showed that the ketoprofen-nicotinamide multicomponent solid gave a lighter infiltration of neutrophil inflammatory cells when compared to the pure ketoprofen group. [ABSTRACT FROM AUTHOR]

The present piece of research work is framed for improving the solubility of ketoprofen by forming co-crystal using fumaric acid as a coformer. Co-crystal of ketoprofen and fumaric acid was prepared by simple solvent-assisted grinding method, containing drug and coformer as independent variables and solubility and % drug release were assumed to be dependent variables. Differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, nuclear magnetic resonance and scanning electron microscopy techniques were used to characterize the preparation of optimized batch of co-crystal and further, evaluated for in vitro and in vivo anti-inflammatory and analgesic activities. Based on results of solubility and dissolution rate studies the formulation showed magnified improvement in both the properties on co-crystallization. The values of Gibbs free energy are negative at all levels of carrier demonstrating spontaneity of the drug solubilization process. The IC50 value of optimized batch of co-crystal formulation and the pure drug was observed as 327.33 μg/ml and 556.11 μg/ml, respectively, demonstrating that co-crystal formulation possesses more percentage protection against protein denaturation than the drug ketoprofen. In vivo (anti-inflammatory and analgesic) activities revealed that optimized batch of co-crystal formulation delivered a rapid pharmacological response in Wistar rats and albino mice when compared with standard drug. [ABSTRACT FROM AUTHOR]

In this work, buckwheat husks (Fagopyrum esculentum) were modified by acid treatment and posteriorly employed to remove the ketoprofen in batch adsorption. The characterization results indicated that a more irregular surface with new empty spaces was generated after acid treatment. The adsorptive process was favored at acidic pH = 3. The dosage of 0.85 g L−1 was fixed for the kinetic and isothermal tests, obtaining good removal and capacity indications. The kinetic studies were better represented by pseudo-second-order, obtaining an experimental capacity of 74.3 mg g−1 for 200 mg L−1 of ketoprofen. An increase in temperature negatively affected the adsorption isotherm curves, resulting in a maximum capacity of 194.1 mg g−1. Thermodynamic results confirmed the exothermic nature of the process with physical forces acting. The adsorbent presented high efficiency in treating a synthetic effluent containing different drugs and salts, 71.2%. Therefore, adsorbent development from buckwheat husks treated with a strong acid is an excellent alternative, given the good removal results and the low cost for its preparation. [ABSTRACT FROM AUTHOR]

Biomaterial-based drug delivery systems for a controlled drug release are drawing increasing attention thanks to their possible pharmaceutical and biomedical applications. It is important to control the local administration of drugs, especially when the drug exhibits problems diffusing across biological barriers. Thus, in an appropriate concentration, it would be released in situ, reducing side effects due to interactions with the biological environment after implantation. A theoretical study based on Molecular Mechanics and Molecular Dynamics methods is performed to investigate possible surface interactions between the amorphous SiO2 surface and the ketoprofen molecules, an anti-inflammatory drug, considering the role of drug concentration. These theoretical results are compared with experimental data obtained by analyzing, through Fourier transform infrared spectroscopy (FT-IR), the interaction between the SiO2 amorphous surface and two percentages of the ketoprofen drug entrapped in a silica matrix obtained via the sol–gel method and dried materials. The loaded drug in these amorphous bioactive material forms hydrogen bonds with the silica surface, as found in this theoretical study. The surface interactions are essential to have a new generation of biomaterials not only important for biocompatibility, with specific structural and functional properties, but also able to incorporate anti-inflammatory agents for release into the human body. [ABSTRACT FROM AUTHOR]

The suggested research focused on the construction of a nanocomposite containing organic-inorganic materials as a pharmaceutical shipper to provide a regulated and preserved release of Ketoprofen and Pentoxifylline to reduce its hazards. The study examined the kinetics and the adsorption isotherms of these agents on layered double hydroxides, chitosan, and chitosan-layered double hydroxide nanocomposites that were prepared chemically and identified by high resolution transmission electron microscope, X-ray diffraction, and Fourier transformation Infra-red Spectroscopy. The results showed controlled and continued free through layer hydroxides, chitosan and chitosan-layered hydroxides. Langmuir was the best for illustrating and fitting the sorption equilibrium of Ketoprofen and Pentoxifylline onto the layered double hydroxides, counteracting Freundlich in Chitosan and Chitosan-layered double hydroxide adsorbents. Chitosan-layered double hydroxides, layered double hydroxides, and Chitosan achieved complete release of Pentoxifylline only. Furthermore, Ketoprofen release from chitosan particles was first order, whereas Pentoxifylline release from chitosan-layered double hydroxide complex was zero order. As a final point, the tested nanocarriers restricted the release of Ketoprofen and Pentoxifylline meticulously. [ABSTRACT FROM AUTHOR]

Background: Allergic contact dermatitis (ACD) and photoallergic contact dermatitis (PACD) to benzophenone present in printing ink have been reported. However, precise chemical analyses and extended photo‐patch tests have not been performed in these cases. Objectives: To determine which components present in a magazine cover are responsible for a patient's skin reaction, to determine the primary sensitizer, and precisely diagnose ACD and PACD. Methods: After initial photo‐patch tests were performed on a patient with a history of reaction to magazine covers after sun exposure, gas chromatography–mass spectrometry and high‐performance liquid chromatography analyses of the magazine covers, and additional photo‐patch tests were performed. Results: The first photo‐patch test results confirmed PACD to ketoprofen and fenofibrate and evoked PACD to the magazine covers. 4‐methyl benzophenone (4‐MBP) and 1‐hydroxy‐cyclohexyl‐phenyl‐ketone (1‐HCPK) were found in the magazine cover. Additional photo‐patch tests confirmed PACD to 1‐HCPK and to benzophenone, and photo‐aggravated ACD to 4‐MBP. The primary sensitizer was ketoprofen. Conclusions: Benzophenones are present in a wide variety of products, without always being listed on the packaging. Patients previously sensitized to other ketones, such as ketoprofen, may react to benzophenones without being able to avoid contact with these molecules. New regulations may be needed for more efficient eviction advice. [ABSTRACT FROM AUTHOR]

Background. Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID), is a potent inhibitor of cyclooxygenase that inhibits the synthesis of prostaglandins. It is widely used as an analgesic, anti-inflammatory, and antipyretic drug. However, there have been reports of a steady increase of allergic reactions to this medication. Material and methods. We describe a case report of a 27-year-old patient who experienced adverse reactions of dyspnea and skin lesions a few minutes after intravenously administered ketoprofen due to pain after FESS (Functional Endoscopic Sinus Surgery). Results. The patient was administered dexamethasone and hydroxyzine, which resulted in clinical improvement. Instead of ketoprofen, the patient was treated with paracetamol (i.v.) in a dose of up to 2 g/day without complications. Conclusions. The described case confirms the risk of allergic reaction following the administration of ketoprofen. This adverse effect is especially dangerous for patients with concomitant respiratory diseases (e.g. asthma), therefore the administration of NSAIDs should be avoided in these patients, and paracetamol should be preferred. [ABSTRACT FROM AUTHOR]

In this study, graphitic carbon nitride was used as a support for CuO/TiO2 nanocomposite and was used for the photodegradation of ketoprofen (KP) in various water qualities. The formation of the CuO/TiO2@GCN nanocomposites was proven using different characterization methods. PXRD and Raman analyses of TiO2 and CuO/TiO2 showed that the composite peaks shifted relative to those of TiO2, showing interactions between the two materials. The morphology of CuO/TiO2@GCN consisted of CuO/TiO2 nanoparticles on the surface of the mat‐like GCN. CuO/TiO2@GCN had a narrower band gap and its photoluminescence emission peak was lower than of TiO2. CuO/TiO2@GCN was found to be the best performing photocatalyst that could be used over 3 cycles without major loss in activity. Also, the material was shown to be able to photocatalyze KP in groundwater. The by‐products of the photodegradation were identified by LC–MS. The electrical energy consumed for this process was 2.66E5 kWh/m3. The superior photocatalytic efficiency of CuO/TiO2@GCN relative to TiO2 was attributed to the increased charged separation and that light of higher wavelength was harvested. [ABSTRACT FROM AUTHOR]

• Racemic imprinting concept for chiral MIP preparation is introduced. • Enantioselective reuptake of S -KTP on racemic imprinted polymer is achieved. • RS -MIP and S -MIP binding sites were characterized using scatchard plot. • Chiral separation of racemic KTP was achieved on an RS -MIP packed SPE cartridge. This work presented a novel racemic imprinting process employing the chiral properties of chitosan monomer. The preparation of racemic ketoprofen (RS -KTP) imprinted polymer (RS -MIP) was conducted using glutaraldehyde as a crosslinker. The nature of elution solvent affected the % desorption ratio suggesting a heterogenous nature of the formed binding sites. Good imprinting was indicated by an imprinting factor of 3.50 for S -KTP. The enantioselectivity of the RS -MIP was indicated by enantioselectivity coefficient of 2.31 and % enantiomeric excess (% ee) of 28.55%. A SPE cartridge packed with RS -MIP enabled resolution of RS -KTP using gradient elution solvent system. Scatchard plot revealed two binding sites types of different affinity towards S -KTP and density observed for the RS -MIP. The binding capacity of RS -MIP showed observed dependence on the % ee of S -KTP indicating its enantioselectivity. The success of using racemic template for the preparation of enantioselective MIP brings a new possibility to achieve enantioseparation of racemic mixtures having very expensive or unavailable pure enantiomers. [ABSTRACT FROM AUTHOR]

Dogs undergo various surgical procedures such as castration, ovariohysterectomy, and other orthopedic procedures, which are known to cause inflammation and pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are very effective analgesics for alleviating postoperative pain in veterinary medicine. Ketoprofen is currently approved in Australia and the United States for treating different painful conditions in dogs. This study evaluated the pharmacokinetic parameters of ketoprofen after intravenous (IV) and transdermal (TD) administration in healthy dogs. A novel transdermal ketoprofen (TDK) formulation containing 20% ketoprofen, dissolved in a combination of 45:45% isopropanol and Transcutol, along with 10% eucalyptus oil, was developed and evaluated for in vitro dermal permeation using Franz diffusion cells. A crossover study was then conducted to determine the pharmacokinetic parameters of the formulation in six dogs following IV ketoprofen (1 mg/kg) and TDK (10 mg/kg) administration. A liquid chromatography–mass spectrometry (LC-M/MS) method was used to measure plasma concentrations of ketoprofen over time, and a non-compartmental analysis determined the pharmacokinetic parameters. The mean terminal elimination half-life (T½ h), AUC0-t (µg·h/mL), and mean residence time (MRT, h) between IV and TDK groups were 4.69 ± 1.33 and 25.77 ± 22.15 h, 15.75 ± 7.72 and 8.13 ± 4.28 µg·h/mL, and 4.86 ± 1.81 and 41.63 ± 32.33 h, respectively. The calculated bioavailability (F%) was ~7%, with a lag time of 30 min to achieve effective plasma concentrations after the application of TDK. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop a novel extended in vitro in vivo correlation (IVIVC) model combined with design of experiment (DoE) that integrates the DoE into IVIVC, which can predict the pharmacokinetics of sustained-release (SR) tablets from their formulation compositions, and vice versa. To develop the extended IVIVC model, ketoprofen was used as a model drug. Nineteen types of ketoprofen SR tablets with different formulation compositions were prepared based on the mixture design and used to derive mathematical relationships between the formulation composition and the in vitro dissolution profiles for DoE. The predictability of the DoE equation was externally validated by using additional seven types of SR formulations with prediction errors (%PE) of less than 11.45%. For the development of IVIVC model, three SR formulations that have fast, medium, and slow drug-releasing rates were selected, and the in vivo pharmacokinetics were assessed in Beagle dogs. The pharmacokinetic properties of ketoprofen SR tablets were described by a population pharmacokinetics (POP-PK) model which incorporated the pH-dependent dissolution of ketoprofen by a time-dependent Hill-type equation. The final POP-PK model could describe the overall in vivo pharmacokinetic profiles and allowed estimation of the in vivo dissolution parameters. The POP-PK model estimated in vivo dissolution parameter, K diss, in vivo were then correlated with the in vitro dissolution parameter, K diss, in vitro by linear regression (R2 = 0.9989), establishing IVIVC. Finally, the equation derived from DoE was introduced to the IVIVC model to develop the extended IVIVC, which connects the formulation composition, in vitro dissolution, and in vivo pharmacokinetic profiles. The average %PE of the final extended IVIVC model was 4.24% for C max and 4.46% and AUC. Finally, the final extended IVIVC was applied to predict the in vivo PK profiles of SR tablets from their formulation compositions as well as to design the optimal formulation to achieve certain target PK profiles. The %PE of the final extended IVIVC model was less than 14.67% for C max and 12.41% for AUC, satisfying the FDA criteria of conventional IVIVC. The present extended IVIVC model may provide a useful tool towards rationalized design and development of new SR formulations. [Display omitted] • Integration of DoE and IVIVC provided a new model-based approach for SR tablets. • The extended IVIVC correlates formulation, dissolution, and in vivo PK. • In vivo PK of an SR tablet could be predicted from its formulation, and vice versa. • This approach may expedite the successful development of SR formulations. [ABSTRACT FROM AUTHOR]

The solution mixture of the non-steroidal anti-inflammatory drugs ketoprofen, meloxicam and tenoxicam was degraded through systems, composed of different photocatalysts based on TiO2 (Fe and Cu) and the hydrogen peroxide oxidant. The monitoring was performed by UV-Vis spectroscopy. Under sunlight radiation, a reduction in peaks was observed with the use of impregnated photocatalysts. After 60 min, the sun/H2O2/Fe-TiO2 system reached degradations of 46.5% and 93.2% at 260 and 367 nm, respectively, and was selected for further studies. The degradation kinetic reached 92 and 96% of degradation after 180 min, for the λ of 260 and 367 nm, respectively. The kinetic curve could be represented by the empirical model proposed by Nichela and co-authors, indicating that besides the heterogeneous photocatalysis that occurs at the surface of the TiO2 there is also the joint effect of the photo-Fenton process. After the treatment, there was no toxicity to cress and lettuce seeds. However, a sensitivity of the thyme seeds to the compounds formed during the treatment was verified. After the fifth treatment cycle, the supported photocatalyst showed degradation higher than 82%. These results indicate that this system is suitable for the treatment of effluents containing pharmaceutical compounds.

Abstract Background To explore the release behavior of ketoprofen enantiomers from alginate-metal-complexes. Five mathematical models of drug release kinetics were investigated. Results Beads of alginate-metal complexes, loaded with racemic ketoprofen, were prepared by the ionotropic method. Divalent (Ca, Ba, Zn) and trivalent (Fe, Al) metals were used in the preparation of single-metal and mixed-metal alginate complexes. In vitro release experiments were carried out in an aqueous phosphate buffer medium at pH = 7.4. The concentrations of ketoprofen released enantiomers were determined using chiral HPLC technique. The obtained data were used to simulate the release kinetic of ketoprofen enantiomers using various mathematical models. The Korsmeyer-Peppas model was the best fit for Ca, Al, and Fe beads. Moreover, alginate-iron beads tend to release the drug faster than all other cases. In contrast, the drug release for alginate-barium complex was the slowest. The presence of barium in alginate mixed-metal complexes reduced ketoprofen release in the case of Fe and Zn, while it increased the release in the case of Al complex. Conclusion In all the studied cases, ketoprofen showed very slow release for both enantiomers over a period exceeded 5 h (10 days in some cases). The release rate modification is possible using different multivalent metals, and it is also feasible by using two different metals for congealing either consecutively or simultaneously.

Aim: The aim of the study was to compare the efficacy of transdermal diclofenac patch with ketoprofen patch as postoperative analgesia after extraction of first premolars bilaterally in both arches for orthodontic purpose. Materials and Methods: A split-mouth technique was used in 52 patients with the age group of 15–25 years for extracting maxillary and mandibular first premolars bilaterally for orthodontic reason. A single ketoprofen patch was used after the extraction of premolars from first and fourth quadrant, whereas for the extraction of second and third quadrant premolars, diclofenac patch was used. All the extractions were performed under local anesthesia. The data were compiled and statistically analyzed using the student's t-test. Results: Mean visual analog scale score for diclofenac and ketoprofen patch was 2.05 (0.75) and 1.09 (0.3), respectively. Thirteen patients required additional medication (25%) and 1 (1.9%) patient with diclofenac and ketoprofen patch, respectively. No major complication or adverse effects were observed in any of the groups. Conclusion: Both diclofenac and ketoprofen transdermal patches are helpful in relieving pain after orthodontic extraction. Patients with diclofenac patch required more additional analgesia within 24 h compared to that with ketoprofen patch. None of the drugs showed any significant adverse effects and were well tolerated by the patients.

The present study reports the generation of 2-hydroxyethyl starch microparticles for co-delivery and controlled release of multiple agents. The obtained microparticles are characterized by using Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction analysis, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. By using ofloxacin and ketoprofen as drug models, the release sustainability of the microparticles is examined at pH 1.2, 5.4, and 6.8 at 37 °C, with Fickian diffusion being found to be the major mechanism controlling the kinetics of drug release. Upon being loaded with the drug models, the microparticles show high efficiency in acting against Escherichia coli and Bacillus cereus. The results suggest that our reported microparticles warrant further development for applications in which co-administration of multiple bioactive agents is required.