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Increasing industrial activity causes the release of chemical compounds into aquatic habitats, including toxic heavy metals like cadmium and medications like ketoprofen, posing considerable ecological concerns. Although previous studies have shown that cadmium and ketoprofen individually cause cognitive impairment, there is a lack of information on the combined neurological effects of the two substances. We investigated the neurological consequences of persistent cadmium exposure in the presence of ketoprofen on adult zebrafish, providing an essential model for understanding cumulative impacts on vertebrate organisms. Behavioral assessments, bioaccumulation rates, biochemical studies, and histopathological exams were conducted over 42 days in authentic environmental settings. The results of our study show that cadmium (10 µg/L) and ketoprofen (10 and 100 µg/L) at environmentally relevant concentrations had a significant impact on locomotor activity, social interactions, and cognitive responses, indicating cumulative neurotoxicity in co‐exposure groups compared to single pollutant groups. Biochemical tests show disturbances in antioxidant defense systems, while histological examinations reveal structural changes in zebrafish brain regions. Ketoprofen influences cadmium accumulation in the brain, underscoring the importance of conducting complete evaluations to understand the intricate interactions between environmental pollutants. This study improves our understanding of the complex interactions between heavy metals and medications, stressing the need to consider combined exposure when assessing the neurological effects on vertebrate models. [ABSTRACT FROM AUTHOR]

A major cause of early embryonic losses is inadequate secretion of progesterone (P4) hormone due to luteal insufficiency in farm animals. Post-mating applications that directly or indirectly increasing serum P4 concentrations have a positive effect on fertility. The aim of this study was to investigate the effect of post-mating administration of ketoprofen on serum P4 concentration and fertility in Akkaraman ewes synchronized with a short-term protocol during the breeding season. Oestrus monitoring ewes after synchronization were hand-mated and randomly assigned to two equal groups (Ketoprofen vs. Control). Ewes in the ketoprofen group (KPG) (n = 40) were administered with ketoprofen (Rifen, Richter pharma, Austria) intramuscularly (im) at a dose of 3 mg/kg on days 9 and 10 after mating. In the control group (CG) ewes (n = 40) were administered with saline im on the same days. Blood samples were collected from ewes in both groups at four different time points of post-mating days (9, 12, 15 and 18 days). The results showed that there were no statistical differences between the KPG and CG groups on fertility parameters; pregnancy rates (85% vs. 72.5%), lambing rates (100% vs. 100%), single birth rates (55.9% vs. 55.2%), multiple birth rates (44.1% vs. 44.8%), litter sizes (1.56 vs. 1.55). In pregnant ewes, serum P4 concentrations on day 18 (4.35 ± 0.34 ng/mL) in the KPG group were higher than (3.27 ± 0.27 ng/mL) in CG group (P < 0.05). It was concluded that post-mating ketoprofen administration have no significant effect on fertility, but significantly increased the serum P4 concentration on day 18 in pregnant ewes. [ABSTRACT FROM AUTHOR]

Ketoprofen is a non-biodegradable drug and is not removed by conventional treatments. The need to remove pharmaceutical compounds from water and wastewater has aroused considerable interest in advanced oxidation processes (AOP), whose effectiveness depends on the generation of reactive free radicals capable of oxidizing and decomposing numerous compounds. Heterogeneous photocatalysis is an efficient method if an active semiconductor is used. In this work, the photodegradation reaction of ketoprofen promoted by TiO2 was studied, analyzing the kinetics obtained by changing variables such as temperature, initial concentration, and quantity of photocatalyst. It was determined that the mechanism is of the Langmuir–Hinshelwood type and that the system is operating in the kinetic regime, while tests at different temperatures have shown that the adsorption of ketoprofen and byproducts are both exothermic. Experimental data were interpreted with reliable models that allow to retrieve quantitatively the kinetic and thermodynamic parameters. [ABSTRACT FROM AUTHOR]

The present study was aimed to ameliorate the issue of solubility and thereby, bioavailability of ketoprofen, a BCS Class II drug. The sustained release matrix tablets (MT) were prepared using surfactant-assisted wet granulation (SAWG) with 1–5% of different surfactants. The tablet characteristics were within the compendial limits. The selected sustained release-compliant matrix tablet formulation containing granules prepared using 3% Soluplus® (MT2) released the drug by swelling-erosion. In human volunteers, MT2 attained the maximum plasma concentration (Cmax) of 5.72µg /ml ± 0.30 h, time to Cmax (Tmax) of 5.56 ± 0.30 h and maintained the plasma concentration above its minimum effective concentration (MEC), 0.7 µg.ml−1 till 24h. A control formulation, prepared from granules without surfactant (MT16), promptly attained Cmax of 9.62 ± 0.76 µg/ml within 1h but rapidly declined to below MEC in 8h. Area under the curve from initial point to infinity (AUC0-∞) of MT2 (78.65 ± 7.64 µg.h.ml−1) was 2.29 folds higher than 34.39 ± 3.06 µg.h.ml−1 of MT16. With decreased Cmax, increased AUC0-∞, delayed Tmax and retained ketoprofen concentration above MEC for longer time, MT2 corresponded with the in-vitro sustained drug release characteristic. There is a likelihood of administration of once-a-day single dose of MT2 without plasma fluctuations, expected from two doses of MT16. SAWG helped developing a swellable-erodible sustained release matrix tablet formulation of ketoprofen with the desired biopharmaceutical and pharmacokinetics properties, merely by addition of Soluplus® in granules and without incorporation of any special ingredients or the major manipulation of the formulative ingredients in the formulation. [ABSTRACT FROM AUTHOR]

Improved solubility and anti-inflammatory (AI) properties are imperative for enhancing the effectiveness of poorly water-soluble drugs, particularly non-steroidal anti-inflammatory drugs (NSAIDs). To address these critical issues, our focus is on obtaining NSAID materials in the form of inclusion complexes (IC) with methyl-beta-cyclodextrin (MCD). Ketoprofen (KTP) is selected as the NSAID for this study due to its potency in treating various types of pain, inflammation, and arthritis. Our objective is to tackle the solubility challenge followed by enhancing the AI activity. Confirmation of complexation is achieved through observing changes in the absorbance and fluorescence intensities of KTP upon the addition of MCD, indicating a 1:1 stoichiometric ratio. Phase solubility studies demonstrated improved dissolution rates after the formation of ICs. Further analysis of the optimized IC is conducted using FT-IR, NMR, FE-SEM, and TG/DTA techniques. Notable shifts in chemical shift values and morphological alterations on the surface of the ICs are observed compared to their free form. Most significantly, the IC exhibited superior AI and anti-arthritic (AA) activity compared to KTP alone. These findings highlight the potential of ICs in expanding the application of KTP, particularly in pharmaceuticals, where enhanced stability and efficacy of natural AIs and AAs are paramount. [ABSTRACT FROM AUTHOR]

Emerging pollutants are a widespread environmental concern, andadsorption represents one of the choices available for the removal of suchcompounds from polluted waters. However, the set‐up of a new adsorption system requiresthe experimental determination of adsorption isotherms and their thoroughmodelling, for the sake of a convenient optimization. In this work, the Campomanesia guazumifolia biomass is adopted as precursor for the synthesis of anew adsorbent and then tested for the adsorption of KTP and 2,4‐D. Theadsorption performances of this biomass are significantly improved through atreatment with sulfuric acid, which allows obtaining higher removal efficiency ofthe target organic molecules. The experimental isotherms are measured at 298 – 328 K and pH 2. An ETAM model is employed for amodeling analysis of the experimental data, for the comprehension of theoccurring adsorption mechanism. Results demonstrated that adsorption of KTP isendothermic and occurs in multilayer with a multimolecular process, in whichthe molecular aggregation can be predicted. On the contrary, the adsorption of 2,4‐D on this functionalized biomass is exothermic. The adsorption energiesresulted to be < 40 kJ mol−1, indicating that physical adsorption forces are involved inthe removal of these organic molecules. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Dalian University of Technology / Dalian Ligong Daxue Xuebao is the property of Journal of Dalian University of Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Improved solubility and anti-inflammatory (AI) properties are imperative for enhancing the effectiveness of poorly water-soluble drugs, particularly non-steroidal anti-inflammatory drugs (NSAIDs). To address these critical issues, our focus is on obtaining NSAID materials in the form of inclusion complexes (IC) with methyl-beta-cyclodextrin (MCD). Ketoprofen (KTP) is selected as the NSAID for this study due to its potency in treating various types of pain, inflammation, and arthritis. Our objective is to tackle the solubility challenge followed by enhancing the AI activity. Confirmation of complexation is achieved through observing changes in the absorbance and fluorescence intensities of KTP upon the addition of MCD, indicating a 1:1 stoichiometric ratio. Phase solubility studies demonstrated improved dissolution rates after the formation of ICs. Further analysis of the optimized IC is conducted using FT-IR, NMR, FE-SEM, and TG/DTA techniques. Notable shifts in chemical shift values and morphological alterations on the surface of the ICs are observed compared to their free form. Most significantly, the IC exhibited superior AI and anti-arthritic (AA) activity compared to KTP alone. These findings highlight the potential of ICs in expanding the application of KTP, particularly in pharmaceuticals, where enhanced stability and efficacy of natural AIs and AAs are paramount.

Objective: Photoallergic reactions due to topical ketoprofen are common. As some simultaneous contact allergies have been described in the literature, we aimed to get an overview of the pattern of reactivity towards common allergens in the baseline series in ketoprofen‐photoallergic individuals. Methods: Using our database, we found 94 patients with photocontact allergy to ketoprofen diagnosed during 1999–2018. Approximately 12 800 patients patch tested with the baseline series during the same time frame served as controls. Data on patch testing with the baseline series of 518 individuals belonging to the general population were obtained from an earlier study, and a comparison of allergy rates was made with the ketoprofen group. Results: Contact allergy to fragrance mix I and Myroxylon pereirae was overrepresented among patients with photocontact allergy to ketoprofen (42.3% vs. 6.6% and 47.9% vs. 6.6%, p < 0.001, respectively). Significant overrepresentation was also shown for 4‐tert‐butylphenolformaldehyde resin (PTBP‐F‐R), phenol formaldehyde resin (PFR‐2), black rubber mix, budesonide (all p < 0.001), and fragrance mix II (p = 0.02). The pattern was similar, but with lower significance levels for fragrance mix II and budesonide, regardless of whether or not the individuals had been photopatch tested because of a suspected photoallergic contact dermatitis from ketoprofen. Conclusion: Contact allergy to fragrance mix I, Myroxylon pereirae, black rubber mix, PFR‐2, PTBP‐FR, and to a somewhat lower extent, to fragrance mix II and budesonide, is common in individuals photoallergic to ketoprofen. It remains to be seen whether sensitisation to ketoprofen leads to simultaneous sensitisation to a number of other, chemically non‐related, substances. [ABSTRACT FROM AUTHOR]

Background: Photoallergic contact dermatitis (PACD) is a delayed hypersensitivity reaction to allergens only in the presence of ultraviolet radiation in sunlight. Photopatch testing (PhotoPT) is necessary to confirm the diagnosis of PACD. There are few published studies of PhotoPT in North America. Objective: To summarise the results of patients photopatch tested by members of the North American Contact Dermatitis Group (NACDG), 2009–2020. Methods: Retrospective analysis of patient characteristics and PhotoPT results to 32 allergens on the NACDG Photopatch Test Series. Results: Most of the 454 tested patients were female (70.3%), 21–60 years old (66.7%) and White (66.7%). There were a total of 119 positive photopatch tests. Sunscreen agents comprised 88.2% of those, with benzophenones responsible for over half of them. Final diagnoses included PACD in 17.2%, allergic contact dermatitis (ACD) in 44.5%, polymorphous light eruption (PMLE) in 18.9% and chronic actinic dermatitis (CAD) in 9.0% of patients. Conclusions: In 454 patients with suspected photosensitivity referred for photopatch testing in North America, approximately one‐fifth had PACD. Sunscreen agents, especially benzophenones, were the most common photoallergens. Other common diagnoses included ACD, PMLE and CAD. Photopatch testing is an important tool for differentiating these conditions. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate and compare the effect of dexamethasone, ketoprofen and cold compress on the quality of life (QoL) following surgical removal of impacted lower third molars (ILTMs). Materials and methods: Eligible patients requiring ILTM extraction with a modified Pederson difficulty index score of 5–6 were recruited. The patients were randomly allocated into Groups A, B and C. Groups A and C received 100 mg of ketoprofen and 8 mg of dexamethasone per-oral respectively, preoperatively. Subjects in group B applied a pre-standardized ice pack over the angle of the mandible for 6 h postoperatively. The QoL questionnaire was administered on postoperative days 1, 2 and 7. Results: In total, seventy-eight subjects completed the study: 46 (59%) were male and had a mean age of 27.8 ± 4.9 years. The groups were similar sociodemographically. The overall QoL and appearance domain score were significantly better in patients on oral dexamethasone on postoperative day 1 than in the other groups. Conclusions: Oral dexamethasone demonstrates better improvement in postoperative QoL and appearance on day 1 following ILTM surgery compared to ice packs and ketoprofen. Although ice packs are readily available, can be used repeatedly and are a low-cost option, more research is necessary to determine their optimum therapeutic use in outpatient settings. Clinical relevance: Oral dexamethasone is superior to ice pack compress and ketoprofen in improving the postoperative QoL in ILTM surgery. Trial registry registration number: PACTR202005593102009 at Pan African Clinical Trial Registry. [ABSTRACT FROM AUTHOR]

Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) whose formulation options are limited due to its low dissolution rate in aqueous media. This research aimed to enhance the solubility of ketoprofen in distilled water and to compare the anti-inflammatory and analgesic effects of its resulting multicomponent crystal with tromethamine. The binary phase diagram of ketoprofen-tromethamine was created across molar ratios ranging from 1:9 to 9:1. The multicomponent crystal comprising ketoprofen and tromethamine in the selected ratio was synthesized using a solvent drop grinding method and subjected to further characterization for thermal properties, crystallinity, chemical groups, and morphology. The dissolution rate assessments were evaluated in CO2-free distilled water. Pharmacological analyses examined the anti-inflammatory and analgesic effects of the multicomponent crystal. The binary phase analysis identified the 5:5 (1:1) molar ratio as optimal in forming a multicomponent crystal. Thermograms and diffractograms revealed crystalline alterations attributed to a new crystalline phase. The new multicomponent crystal exhibited approximately 2.7 times higher dissolution rate after 30 minutes, outperforming pure ketoprofen. Pharmacological assessments demonstrated superior analgesic effects of the multicomponent crystal. In summary, the ketoprofen-tromethamine cocrystal in 1:1 molar ratio offers enhanced dissolution rate and provides better analgesic activity than ketoprofen alone.

Due to unique structural characteristics and chiral environment, β‐cyclodextrin (β‐CD) has a strong chiral separation ability. 4‐Chlorophenyl isocyanate (4CPI) also plays an important role in separating chiral drugs. In this paper, a chiral stationary phase: 4‐CPI‐β‐CD stationary phase (4CPI‐β‐CD@PMMA) was designed and prepared. Polymethyl methacrylate (PMMA) microspheres with uniform particle size and good monodispersity were prepared by modified seed polymerization and seed expansion methods. Using diazo resin as a coupling agent, PMMA microspheres were connected with 4CPI‐β‐CD to prepare a stationary phase with chiral recognition ability. PMMA microspheres and 4CPI‐β‐CD were also characterized. Compared with the traditional silica gel column, PMMA microspheres have higher preparation efficiency, better monodispersity, and better mechanical properties as chromatographic fillers. Finally, the chiral separation of ketoprofen was carried out by reversed‐phase high‐performance liquid chromatography, and the separation conditions were optimized. This paper is a good idea for the preparation of the chiral stationary phase. [ABSTRACT FROM AUTHOR]

This study explored the antimicrobial effects of ketoprofen, piroxicam, and celecoxib alone or combined with calcium hydroxide (CH) against two strains of Enterococcus faecalis (E. faecalis) and assessed the influence of such combinations on the pH of CH. Minimum inhibitory concentrations (MICs) of the three tested NSAIDs were determined. Tested pastes were placed into wells punched in seeded agar plates and the bacterial inhibition zones were measured. Antibiofilm activity was assessed against 3 weeks of biofilm induced in bovine dentine blocks. The pH of the pastes was measured at four-time intervals. MIC values were 3.12, 25, and 25 mg/ml for ketoprofen, piroxicam, and celecoxib, respectively, and were similar for both bacterial strains except for celecoxib, which showed 8% growth at the highest tested concentration against vancomycin-resistant E. faecalis. Ketoprofen had the largest mean inhibition zone that was comparable to CH. None of the six tested pastes exhibited antibiofilm activity of a significant level in comparison to CH. A noticeable increase in the antibiofilm activity was found when 20% NSAIDs were added to CH while maintaining an alkaline pH. Ketoprofen was found to be the most effective among the tested NSAIDs. Although its effect was comparable to CH, adding ketoprofen at a ratio of 20% resulted in 50% higher antimicrobial action than CH alone. Accordingly, incorporating NSAIDs in inter-appointment dressing has the potential to utilize their anti-inflammatory, local analgesic, and antibacterial actions, which overcome the limitations of CH and improve the outcome of root canal treatment. [ABSTRACT FROM AUTHOR]

Ketoprofen is a non-steroidal, anti-inflammatory drug frequently incorporated in topical dosage forms which are an interesting alternatives for oral formulations. However, due to the physiological barrier function of skin, topical formulations may require some approaches to improve drug permeation across the skin. In this study, ketoprofen-loaded microemulsion-based gels with the addition of menthol, commonly known for absorption-enhancing activity in dermal products, were investigated. The main objective of this study was to analyze the physicochemical properties of the obtained gels in terms of topical application and to investigate the correlation between the gel composition and its mechanical properties and the drug release process. Microemulsion composition was selected with the use of a pseudoternary plot and the selected systems were tested for electrical conductivity, viscosity, pH, and particle diameter. The polymer gels obtained with Carbopol® EZ-3 were subjected to rheological and textural studies, as well as the drug release experiment. The obtained results indicate that the presence of ketoprofen slightly decreased yield stress values. A stronger effect was exerted by menthol presence, even though it was independent of menthol concentration. A similar tendency was seen for hardness and adhesiveness, as tested in texture profile analysis. Sample cohesiveness and the drug release rate were independent of the gel composition. [ABSTRACT FROM AUTHOR]

AbstractThe growing concern about pollution and toxicity in aquatic as well as terrestrial organisms is predominantly caused due to waterborne exposure and poses a risk to environmental systems and human health. This study addresses the co-toxic effects of cadmium (Cd) and ketoprofen (KPF), representing heavy metal and pharmaceutical discharge pollutants, respectively, in aquatic ecosystems. A 96-h acute toxicity assessment was conducted using zebrafish embryos. The results indicated that high dosages of KPF (10, 15, and 100 µg/mL) and Cd (10 and 15 µg/mL) reduced survivability and caused concentration-dependent deformities such as scoliosis and yolk sac edema. These findings highlight the potential defects in development and metabolism, as evidenced by hemolysis tests demonstrating dose-dependent effects on blood cell integrity. Furthermore, this study employs adult zebrafish for a 42-day chronic exposure to Cd and KPF (10 and 100 µg/L) alone or combined (10 + 10 and 100 + 100 µg/L) to assess organ-specific Cd and KPF accumulation in tissue samples. Organ-specific accumulation patterns underscore complex interactions impacting respiratory, metabolic, and detoxification functions. Prolonged exposure induces reactive oxygen species formation, compromising antioxidant defense systems. Histological examinations reveal structural changes in gills, gastrointestinal, kidney, and liver tissues, suggesting impairments in respiratory, osmoregulatory, nutritional, and immune functions. This study emphasizes the importance of conducting extensive research on co-toxic effects to assist with environmental risk assessments and safeguard human health and aquatic ecosystems. [ABSTRACT FROM AUTHOR]

Given that oxidative stress (OS) occurs as one of the complications of general anesthesia and surgical procedures, practicing the best and safest anesthesia regimen can have a significant share in various surgeries. So, this study compared the effects of non-steroidal anti-inflammatory drugs (NSAIDs) such as ketoprofen (KTP) and meloxicam (MLX) on OS through the glutathione pathway after the ketamine-xylazine (K-X) anesthesia and ulcer induction in rats to suggest post-operative regimens with promising analgesic and anti-inflammatory effects.80 healthy adult male Wistar rats, were examined in this study. To obtain the baseline value cardiac blood collected of five rats, and the remaining 75 animals were randomized into three groups of 25, including (i) the control group receiving physiological serum, (ii) the experimental group 1 taking KTP, (iii) the experimental group 2, administered by MLX and all three groups received K-X combination IP after 30 min. Then, a full-thickness ulcer was induced under standard conditions, and the blood samples were collected from groups at T0, T30m, T60m, T24h, and T48h. The serum levels of the desired markers were measured. The study results revealed that the administration of K-X as an anesthetic agent made some changes in the markers of the OS-related glutathione (GSH) pathway. Moreover, KTP and MLX, significantly (p < 0.05) augmented the reduced GSH (rGSH), lowered the GSSG, increased the total values of the glutathione disulfide (GSSG) and the rGSH, reduced the rGSH/GSSG ratio, and accelerated the glutathione peroxidase (GPx) activity, but they had high inhibitory effects on the glutathione reductase (GR). Accordingly, both drugs could maintain the balance between the OS markers, caused by general anesthesia. In general, KTP can be a suitable regimen in surgeries wherein analgesia is of importance for less than 24 h, but MLX can be a preferable option if longer analgesia is needed for more than 24 h.

This investigation examines the adsorption and elimination of the anti-inflammatory medication ketoprofen (KTP) in relation to a newly developed magnetic thorium metal-organic framework (MTh-MOF). The study found that KTP absorption on MTh-MOF resulted in a reduction in pore volume, pore size, and surface area, as revealed by N2 adsorption/desorption isotherm analysis used to evaluate the characteristics of the MTh-MOF. Scanning electron microscopy (SEM) showed that the pore radius of MTh-MOF decreased from 1.68 nm to 0.82 nm, demonstrating a consistent and uniform structure. Fourier-transform infrared (FT-IR) spectroscopy was employed to identify the functional groups present in MTh-MOF, while X-ray photoelectron spectroscopy (XPS) was used to confirm the compound's structure. The optimal conditions for achieving a high adsorption capacity were found to be at pH 6 and a MTh-MOF dose of 0.02 g. The results indicated that MTh-MOF displayed a high capacity for absorbing KTP, with the adsorption data fitting well with pseudo-second-order kinetic models and the Langmuir isotherm. The adsorption capacity of MTh-MOF for KTP was determined to be 518 mg/g. The adsorption energy of 28.26 kJ mol−1 suggested that chemisorption was the predominant mode of adsorption. The process of KTP adsorption on MTh-MOF was observed to be spontaneous, endothermic, and random, as evidenced by the temperature-dependent increases in the thermodynamic parameters (ΔGo, ΔHo, and ΔSo). The adsorption process was optimized using Response Surface Methodology and Box-Behnken design (RSM, BBD). Aromatic rings interact via π-π bonding, while chemisorption involves the development of chemical interactions between the adsorbate and adsorbent. Additionally, electrostatic interactions arise from the attraction or repulsion of charges between the adsorbate and adsorbent, and pore-filling occurs when the adsorbate fills the adsorbent's pores. In order to understand the electrical properties, reactivity, and shape of KTP, density functional theory (DFT) was utilized.

Long term (200 h) continuous operation of a submerged photocatalytic membrane reactor utilizing direct contact membrane distillation (SPMR-DCMD) is presented. Various types of feed contaminated with ketoprofen were treated: brackish water (BW), seawater (SeaW), and secondary wastewater effluent (SE). Ketoprofen decomposition after 24 h exceeded 99.5 %, regardless of feed type. The distillate showed no toxicity to Aliivibrio fischeri. A significant decrease in flux after 100–124 h of BW and SeaW treatment occurred due to scaling, while for SE the flux remained almost constant for 200 h. This indicates that a shorter study would not allow a proper analysis of the process. A scaling layer was formed regardless of feed type, and the formation of CaSO4⋅2H2O, CaCO3 or (Ca,Mg)CO3 was proved. The porous structure of the deposit during SE treatment prevented significant flux deterioration. The formed TiO2 layer protected the membrane from damage by the growing salt crystals.

Deep eutectic solvents (DESs) are commonly used in pharmaceutical applications as excellent solubilizers of active substances. This study investigated the tuning of ibuprofen and ketoprofen solubility utilizing DESs containing choline chloride or betaine as hydrogen bond acceptors and various polyols (ethylene glycol, diethylene glycol, triethylene glycol, glycerol, 1,2-propanediol, 1,3-butanediol) as hydrogen bond donors. Experimental solubility data were collected for all DES systems. A machine learning model was developed using COSMO-RS molecular descriptors to predict solubility. All studied DESs exhibited a cosolvency effect, increasing drug solubility at modest concentrations of water. The model accurately predicted solubility for ibuprofen, ketoprofen, and related analogs (flurbiprofen, felbinac, phenylacetic acid, diphenylacetic acid). A machine learning approach utilizing COSMO-RS descriptors enables the rational design and solubility prediction of DES formulations for improved pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Four alkaline earth metal complexes of ketoprofen (Hket) and indomethacin (Hind) were synthesized and characterized: [Ca(ket)2(H2O)2]n (1), [Mg(ket)2(H2O)2] (2), [Ca(ind)2(EtOH)2]n (3), and [Mg(ind)2(EtOH)2] (4). All compounds were studied by elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Crystal structures of 1 and 3 were determined by single crystal X‐ray diffraction technique T=100 K. The structure of 1 is dominated by a one‐dimensional coordination polymer, while 3 is formed by a two‐dimensional layer stabilized by the calcium zig‐zag chains and π⋅⋅⋅π stacking interactions. Crystal packing arrangements were characterized by fingerprint plots (FPs) that were derived from the Hirshfeld surfaces (HSs). The antioxidant and antimicrobial activities of complexes were evaluated against Gram‐positive and Gram‐negative bacteria as well as yeasts. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these drugs exhibit various other pleiotropic effects in several cells, including platelets. Within this article, the multifaceted properties of NSAIDs on platelet functions, activation and viability, as well as their interaction(s) with established antiplatelet medications, by hindering several platelet agonists' pathways and receptors, are thoroughly reviewed. The efficacy and safety of NSAIDs as adjunctive therapies for conditions involving inflammation and platelet activation are also discussed. Emphasis is given to the antiplatelet potential of commonly administered NSAIDs medications, such as ibuprofen, diclofenac, naproxen and ketoprofen, alongside non-opioid analgesic and antipyretic medications like paracetamol. This article delves into their mechanisms of action against different pathways of platelet activation, aggregation and overall platelet functions, highlighting additional health-promoting properties of these anti-inflammatory and analgesic agents, without neglecting the induced by these drugs' side-effects on platelets' functionality and thrombocytopenia. Environmental issues emerging from the ever-increased subscription of these drugs are also discussed, along with the need for novel water treatment methodologies for their appropriate elimination from water and wastewater samples. Despite being efficiently eliminated during wastewater treatment processes on occasion, NSAIDs remain prevalent and are found at significant concentrations in water bodies that receive effluents from wastewater treatment plants (WWTPs), since there is no one-size-fits-all solution for removing all contaminants from wastewater, depending on the specific characteristics of the wastewater. Several novel methods have been studied, with adsorption being proposed as a cost-effective and environmentally friendly method for wastewater purification from such drugs. This article also presents limitations and future prospects regarding the observed antiplatelet effects of NSAIDs, as well as the potential of novel derivatives of these compounds, with benefits in other important platelet functions. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Faculty of Pharmacy of Ankara University / Ankara Üniversitesi Eczacilik Fakültesi Dergisi is the property of Ankara University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Ketoprofen (KTP) is a non-steroidal anti-inflammatory drug (NSAID) used as an analgesic, antipyretic and anti-inflammatory agent in human and veterinary medicine. Although KTP is used in the treatment of diseases such as musculoskeletal inflammation, endotoxemia, pneumonia, enteritis in sheep and minor surgical procedures such as dehorning and castration there is no information about its safety. The aim of this study is to determine the effect of KTP on biochemical and coagulation parameters following intramuscular (IM) administration of different doses of KTP to lambs. In the study, 18 clinically healthy lambs were randomly divided into three groups of 6 animals each. KTP was administered IM to lambs at doses of 1.5, 3 and 6 mg/kg. Biochemical and coagulation parameters were evaluated by taking blood samples before drug administration (0 hour) and at 24 hours and 48 hours after administration. No local or systemic side effects were observed in lambs after the administration of KTP at different doses. The aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) values at 24 hours significantly increased compared to 0 hours in all dosage groups (p<0.05). KTP did not cause a significant change in albumin (ALB), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine (CRE), CK and LDH values in different dose groups. The AST value was only significantly higher in the 6 mg/ kg dose group compared to the 1.5 mg/kg dose group at 24 hours (p<0.05). Although there was no statistically significant difference in intragroup prothrombin time (PT), fibrinogen and D-dimer levels in all dose groups, a significant increase was observed in the activated partial thromboplastin time (aPTT) value of 6 mg/kg dose group at the 24 hours compared to the 0 hour (p< 0.05). As a result, after IM administration of 1.5, 3 and 6 mg/kg, increased CK and LDH values, which may be associated with muscle damage, may limit use of KTP via IM injection in lambs. [ABSTRACT FROM AUTHOR]

AbstractThe primary goal of this research was to investigate pH-triggered colon-specific ketoprofen-loaded microspheres (C-SKLM) using Eudragit S-100 as a pH-dependent polymer. The formulation was optimized using the Box-Behnken design. The suggested C-SKLM formulation with the amount of ketoprofen = 189.09 mg, the amount of Eudragit-100 = 600 mg, and the paddle speed = 400 rpm showed a considerable particle size (106 µm), drug encapsulation efficacy (79.67%), and % cumulative drug release at 5th hr (8.62) and 10th hr (92.62) for oral administration. Microphotographs of scanning electron microscopy indicated that the optimized C-SKLM was smooth and spherical. The differential scanning calorimetry and X-ray powder diffraction studies have shown that ketoprofen was dispersed in the polymer in its optimized C-SKLM formulation, and the spectra from the Fourier transform infrared study have shown no significant drug-polymer interaction. Ex-vivo permeation studies on isolated rat gastro-intestinal segments revealed that the maximum amount of ketoprofen permeated after 2 h through the isolated stomach (0.559 ± 0.049 mg), small intestine (1.36 ± 0.226 mg), and colon (0.972 ± 0.068 mg) was observed for ketoprofen pure. In contrast, a significantly lesser amount of the drug was permeated through the stomach (0.1 ± 0.025 mg) and small intestine (0.28 ± 0.1 mg) than the colon (0.697 ± 0.23 mg) from the ketoprofen-loaded microspheres formulation. In-vitro and ex-vivo permeation studies suggest that the developed C-SKLM could be helpful for the effective management of early morning symptoms due to rheumatoid arthritis by delaying the release by targeting the colon. [ABSTRACT FROM AUTHOR]

An electrochemical sensor for detecting ketoprofen was constructed by in-situ grown copper cobaltate (CuCo2O4) nanoneedle arrays on a carbon cloth (CC) substrate. The resulting porous nanoneedle arrays not only expose numerous electrochemically active sites but also significantly enhance the electrochemical apparent active area and current transmission efficiency. By leveraging its electrochemical properties, the sensor achieves an impressive detection limit for ketoprofen of 0.7 pM, with a linear range spanning from 2 pM ~ 2 µM. Furthermore, the sensor exhibits remarkable reproducibility, anti-interference capabilities, and stability. Notably, the developed sensor also performed ketoprofen detection on real samples (including drug formulations and wastewater) and demonstrated excellent recognition ability. These exceptional performances can be attributed to the direct growth of CuCo2O4 nanoneedle arrays on the CC substrate, which facilitates a robust electrical connection, provides abundant electrocatalytic active sites, and expands the apparent active area. Consequently, these improvements contribute to the efficient trace detection capabilities of the ketoprofen sensor. [ABSTRACT FROM AUTHOR]

Despite rapid progress in tissue engineering, the repair and regeneration of bone defects remains challenging, especially for non-homogenous and complicated defects. We have developed and characterized biodegradable drug-eluting scaffolds for bone regeneration utilizing direct powder extrusion-based three-dimensional (3D) printing techniques. The PLGA scaffolds were fabricated using poly (lactic-co-glycolic acid) (PLGA) with inherent viscosities of 0.2 dl/g and 0.4 dl/g and ketoprofen. The effect of parameters such as the infill, geometry, and wall thickness of the drug carrier on the release kinetics of ketoprofen was studied. The release studies revealed that infill density significantly impacts the release performance, where 10% infill showed faster and almost complete release of the drug, whereas 50% infill demonstrated a sustained release. The Korsmeyer–Peppas model showed the best fit for release data irrespective of the PLGA molecular weight and infill density. It was demonstrated that printing parameters such as infill density, scaffold wall thickness, and geometry played an important role in controlling the release and, therefore, in designing customized drug-eluting scaffolds for bone regeneration. [ABSTRACT FROM AUTHOR]

A reversed-phase high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of the potential impurities of dexketoprofen, including the distomer R-ketoprofen. After screening the separation capability of four polysaccharide columns (Lux Amylose-1, Lux Amylose-2, Lux Cellulose-1 and Lux Cellulose-2) in polar organic and in reversed-phase modes, appropriate enantioseparation was observed only on the Lux Amylose-2 column in an acidified acetonitrile/water mixture. A detailed investigation of the mobile phase composition and temperature for enantio- and chemoselectivity showed many unexpected observations. It was observed that both the resolution and the enantiomer elution order can be fine-tuned by varying the temperature and mobile phase composition. Moreover, hysteresis of the retention times and enantioselectivity was also observed in reversed-phase mode using methanol/water mixtures on amylose-type columns. This could indicate that the three-dimensional structure of the amylose column can change by transitioning from a polar organic to a reversed-phase mode, which affects the enantioseparation process. Temperature-dependent enantiomer elution order and rare enthalpic/entropic controlled enantioseparation in the operative temperature range were also observed in reversed-phase mode. To find the best methodological conditions for the determination of dexketoprofen impurities, a full factorial optimization design was performed. Using the optimized parameters (Lux Amylose-2 column with water/acetonitrile/acetic acid 50/50/0.1 (v/v/v) at a 1 mL/min flow rate at 20 °C), baseline separations were achieved between all compounds within 15 min. Our newly developed HPLC method was validated according to the current guidelines, and its application was tested on commercially available pharmaceutical formulations. According to the authors' knowledge, this is the first study to report hysteretic behavior on polysaccharide columns in reversed-phase mode. [ABSTRACT FROM AUTHOR]

A simple, sensitive and quick HPLC method was developed for the determination of ketoprofen in cell culture media (EMEM, DMEM, RPMI). Separation was performed using a gradient on the C18 column with a mobile phase of acetonitrile and miliQ water acidified by 0.1 % (v/v) formic acid. The method was validated for parameters including linearity, accuracy, precision, limit of quantitation and limit of detection, as well as robustness. The response was found linear over the range of 3–100 μg/mL as demonstrated by the acquired value of correlation coefficient R2=0.9997. The described method is applicable for determination of various pharmacokinetic aspects of ketoprofen in vitro. [ABSTRACT FROM AUTHOR]

Ketoprofen is an anti‐inflammatory drug that is commonly administered to racehorses for the alleviation of musculoskeletal pain and inflammation. This study represents a comprehensive examination of the metabolism (in vivo and in vitro), pharmacokinetics and ex vivo pharmacodynamics, of ketoprofen in horses. The in vitro metabolism as well as specific enzymes responsible for metabolism was determined by incubating liver microsomes and recombinant CYP450 and UGT enzymes with ketoprofen. For the in vivo portion, 15 horses were administered a single intravenous dose of 2.2‐mg/kg ketoprofen. Blood and urine samples were collected prior to and up to 120 h post‐drug administration. Additional blood samples were collected at select time points and were stimulated with calcium ionophore or lipopolysaccharide, ex vivo, to induce eicosanoid production. Drug, metabolite, and eicosanoid concentrations were determined using LC–MS/MS. Incubation of ketoprofen with equine liver microsomes generated 3‐hydroxy ketoprofen, an unidentified hydroxylated metabolite, and ketoprofen glucuronide. Recombinant equine CYP2C23 produced the greatest amount of hydroxylated ketoprofen and recombinant equine UGT1A2 generated ketoprofen glucuronide. Dihydro, 3‐hydroxy, and glucuronide metabolites were identified in blood and urine samples. The Vdss was 0.280, 0.385, and 0.319 L/kg for total ketoprofen, S (+) ketoprofen, and R (−) ketoprofen, respectively. The mean half‐life was 6.01 h for total ketoprofen, 2.22 h for S (+) ketoprofen, and 1.72 h for R (−) ketoprofen. Stimulation of ketoprofen‐treated blood with lipopolysaccharide and calcium ionophore resulted in an inhibition of TXB2, PGE2, PGF2alpha, LTB4, and 15(s)‐HETE production for up to 120 h post‐drug administration. [ABSTRACT FROM AUTHOR]

The double layer adsorption of sulfamethoxazole, ketoprofen and carbamazepine on a phosphorus carbon-based adsorbent was analyzed using statistical physics models. The objective of this research was to provide a physicochemical analysis of the adsorption mechanism of these organic compounds via the calculation of both steric and energetic parameters. Results showed that the adsorption mechanism of these pharmaceuticals was multimolecular where the presence of molecular aggregates (mainly dimers) could be expected in the aqueous solution. This adsorbent showed adsorption capacities at saturation from 15 to 36 mg/g for tested pharmaceutical molecules. The ketoprofen adsorption was exothermic, while the adsorption of sulfamethoxazole and carbamazepine was endothermic. The adsorption mechanism of these molecules involved physical interaction forces with interaction energies from 5.95 to 19.66 kJ/mol. These results contribute with insights on the adsorption mechanisms of pharmaceutical pollutants. The identification of molecular aggregates, the calculation of maximum adsorption capacities and the characterization of thermodynamic behavior provide crucial information for the understanding of these adsorption systems and to optimize their removal operating conditions. These findings have direct implications for wastewater treatment and environmental remediation associated with pharmaceutical pollution where advanced adsorption technologies are required.

The treatment of aseptic inflammation has always been a clinical challenge. At present, non-steroidal drug-loaded microspheres have been widely used in the treatment of aseptic inflammation due to their excellent injectable and sustained release capabilities. In this study, ketoprofen-loaded shellac microspheres (Keto-SLAC) were prepared by electrospray. Alterations of Keto-SLAC morphology was observed in response to changed shellac concentration in ethanol solution through electrospray. Further examination revealed that ketoprofen presented as amorphous solid dispersion in the shellac microspheres. Most importantly, it was also shown that ketoprofen can be slowly released from the shellac matrix for up to 3 weeks. In vitro cell experiments verified that the microspheres had favorable cell compatibility. We therefore proposed that the prepared microspheres, being readily available in use in a variety of clinical settings through topical application, have promising therapeutic potential for the treatment of aseptic inflammation.

Objective. A comparative assessment of the efficacy and safety of the preemptive use of ibuprofen and ketoprofen in patients undergoing elective surgery under general anesthesia.Material and methods. A multicenter randomized prospective study included 58 patients grouped into 2 arms. Ibuprofen 800 mg in Group 1 (N=32), and ketoprofen 100 mg in Group 2 (N=26) were administered intravenously 30 minutes prior to surgical procedure, and afterwards every 12 hours during patient’s stay in the intensive care unit. Efficacy and safety were assessed using a visual analog scale (VAS), patient’s need in opioid analgesics, laboratory parameters (serum levels of cortisol, cystatin C, CBC, coagulogram, TEG) and instrumental methods (algesimetry — qNOX).Results. VAS values were 32.4% lower in Group 1 vs Group 2 in the immediate postoperative period, P=0.003. By the end of Day 1 this difference was no longer visible following the use of promedol. There was a correlation between qNOX values at the end of surgery and VAS values at patient’s waking up from anesthesia (P=0.0007). Cortisol plasma concentrations in groups 1 and 2 did not differ significantly, P=0.105. The average daily promedol consumption in Groups 1 and 2 was 42±17.5 mg/day and 50±19.7 mg/day, respectively, P=0.022. Cystatin C concentrations in the first morning after surgery was 0.95±0.29 mg/l in the ibuprofen group, and 1.19±0.43 mg/l — in the ketoprofen group, P=0.027. Signs of renal dysfunction were documented in 4 out of 32 patients (12, 5%) from Group 1, and in 10 of 26 (38.5%) patients from Group 2 since the end of surgery and up to the first postop morning, the Chi-squared value was 0.031. Hemostasis was not affected by NSAIDs use in both groups.Conclusion. Ibuprofen provided more powerful analgesia, than ketoprofen in the postoperative period, while during surgical procedure both drugs showed similar anlgesic efficacy. Patients on ibuprofen required significantly fewer additional boluses of opioid analgesics. Both drugs showed no clinically significant effect on hemostasis and hematopoiesis. More rare occurrence of renal dysfunction in Group 1 patients is indicative of lower nephrotoxicity of ibuprofen.