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In this study, poly (lactic acid-glycolic acid) (PLGA) nanoparticles loaded with anti-inflammatory drug ketoprofen (KET) were prepared and then coated with platelet membrane (PLTM) to form KET@PLTM-PLGA nano-particles (NPs). The particle size of the KET@PLTM-PLGA NPs is 176 nm and the surface protein is the same as that of PLTM. The results of confocal microscopy and flow cytometry showed that the KET@PLTM-PLGA NPs uptake of RAW264.7 induced by LPS was significantly higher than that of KET@PLGA NPs, without PLTM, which was due to the binding of P-selectin to CD44 receptors on the surface of RAW264.7 cells induced by LPS on the surface of PLTM. Compared with other KET preparations, KET@PLTM-PLGA NPs have better anti-inflammatory effect. PLGA nanoparticles loaded with anti-inflammatory drug ketoprofen (KET) were prepared, and then coated with platelet membrane (PLTM) to form KET@PLTM-PLGA NPs. The NPs have great anti-inflammatory effect. [ABSTRACT FROM AUTHOR]

Chromobacterium violaceum is a Gram-negative, saprophytic bacterium that can infect humans and its virulence may be regulated by quorum sensing via N-acyl homoserine lactones. A virtual screening study with plant compounds and nonsteroidal anti-inflammatory drugs for inhibition of C. violaceum quorum sensing system has been performed. In vitro evaluation was done to validate the in silico results. Molecular docking showed that phytol, margaric acid, palmitic acid, dipyrone, ketoprofen, and phenylbutazone bound to structures of CviR proteins of different C. violaceum strains. Phytol presented higher binding affinities than AHLs and furanones, recognized inducers, and inhibitors of quorum sensing, respectively. When tested in vitro, phytol at a non-inhibitory concentration was the most efficient tested compound to reduce phenotypes regulated by quorum sensing. The results indicate that in silico compound prospection to inhibit quorum sensing may be a good tool for finding alternative lead molecules. [ABSTRACT FROM AUTHOR]

In this study, the pharmacokinetics of ceftriaxone (40 mg/kg) was determined following a single intravenous (IV) administration of ceftriaxone alone and co‐administration with ketoprofen (3 mg/kg) or tolfenamic acid (2 mg/kg) in sheep. Eight healthy Akkaraman sheep (2.4 ± 0.3 years and 44 ± 4 kg of body weight) were used. The study was carried out according to the longitudinal design in three periods with a 15‐day washout period between administrations. In the first period, sheep received ceftriaxone alone via an IV injection. In the second and third periods, the same sheep received ceftriaxone in combination with ketoprofen and tolfenamic acid, respectively. Plasma concentrations of ceftriaxone were assayed by high‐performance liquid chromatography and analyzed using non‐compartmental analysis. Following the administration of ceftriaxone alone, the elimination half‐life (t1/2ʎz), area under the plasma concentration–time curve from zero (0) hours to infinity (∞) (AUC0‐∞), total clearance (ClT), and volume of distribution at steady state were 1.42 h, 182.41 h*µg/ml, 0.22 L/h/kg, and 0.17 L/kg, respectively. While ketoprofen and tolfenamic acid significantly increased the t1/2ʎz and AUC0‐∞ of ceftriaxone, they significantly reduced the ClT. Ceftriaxone (40 mg/kg, IV) in concurrent use with ketoprofen and tolfenamic acid can be administrated at the 12 h dosing intervals to maintain T> minimum inhibitory concentration (MIC) values above 60% in the treatment of infections caused by susceptible pathogens with the MIC value of ≤0.75 and ≤1 μg/mL, respectively, in sheep with an inflammatory condition. [ABSTRACT FROM AUTHOR]

To compare the efficacy and safety of topical nonsteroidal anti-inflammatory drugs (NSAIDs) against placebo and active controls for improving pain and physical function of patients with knee osteoarthritis (OA). We hypothesize that topical NSAIDs will be safe and effective for relieving symptoms in patients with knee OA. The authors performed a systematic review according to the PRISMA guidelines, searching PubMed, EMBASE, and Cochrane databases. Randomized control trials that investigated topical NSAIDs that are widely available in many countries against both placebo and active controls in primary knee osteoarthritis were included. Studies that investigated other treatment modalities or treated nonspecific OA were excluded. A meta-analysis was performed to quantify the effect sizes and heterogeneity of the NSAIDs used. Upon initial search, 259 records were identified with 18 studies remaining after duplicate removal, abstract, and full-text screening. All NSAIDs demonstrated statistically significant reduction in at least one parameter of OA symptoms. The majority of included studies (66.7%) evaluated diclofenac. In the meta-analysis, standardized mean differences (SMD) of topical NSAIDs versus placebo were calculated and interpreted as having moderate effect size for improvement in pain (0.365, 95% confidence interval (CI) 0.240, 0.490) and physical function (0.354, 95% CI 0.268, 0.493). With regard to safety, studies that used patches or dimethyl sulfoxide (DMSO) in the carrier reported a higher incidence of adverse events (AEs) than other carriers. Skin AEs were higher in the treatment group than the placebo group and gastrointestinal AEs were lower in the treatment group than placebo. Topical diclofenac and ketoprofen are the most rigorously studied topical NSAIDs in the treatment of knee OA and have demonstrated the most significant reduction in pain and improvement of function. Ibuprofen was effective for pain relief and physical function improvement, but more high-powered studies are needed to make a confident comparison of efficacy. Additionally, the 'carrier' used to deliver the topical NSAID has an impact on the adverse event profile. This has safety implications for prescribers and pharmaceutical development. Topical diclofenac is widely available internationally and is the only topical NSAID approved for over-the-counter use in the US. It should be recommended to patients as a first-line conservative management for OA of the knee. [ABSTRACT FROM AUTHOR]

In the present study, ketoprofen-p-aminobenzoic acid (KP-PABA) co-crystal was prepared, to advance solubility and dissolution rate of drug, by solvent evaporation technique employing central composite experimental design. The optimized batch as recommended by the experimental design was characterized by FTIR, DSC, XRD, SEM, and NMR studies and further, evaluated for in-vitro and in-vivo anti-inflammatory and analgesic activities. The solubility and % drug release of different batches of co-crystal was found to be between 34.20–60.11 µg/ml and 68.11–93.45%, respectively. Physical characterization by X-ray diffraction spectra and differential scanning calorimetric studies confirmed the crystallinity of prepared co-crystal. The IC50 value of optimized batch of co-crystal formulation and pure drug was observed as 248.79 µg/ml and 524.40 µg/ml, respectively, displaying that co-crystal formulation possesses more percentage protection against protein denaturation than the drug ketoprofen. The results of in-vivo anti-inflammatory activity carried out by rat paw edema method revealed that the optimized batch of co-crystal preparation provided a significant % inhibition in paw volume in contrast to standard drug in wistar rats. Hence, the crystalline molecular complex of ketoprofen with p-aminobenzoic acid was documented that set out an improvement in solubility and also in anti-inflammatory activity of the drug in wistar rats. [ABSTRACT FROM AUTHOR]

Purpose: Ketoprofen (KETO) is a traditional non-steroidal anti-inflammatory drug (NSAIDs) with good analgesic and antipyretic effects. However, as NASIDs, the toxicity of KETO towards gastrointestinal (GI) system might limit its clinical use. S-propargyl-cysteine (SPRC) is an excellent endogenous H2S donor showed wide application in the field of anti-inflammation, anti-oxidative stress, or even the protection of cardiovascular system through the elevation of endogenous H2S concentration. As recently studies reported, co-administration of H2S donor might potentially mitigate the GI toxicity and relevant side effects induced by series of NSAIDs. Methods: In this study, we established a SPRC and KETO co-encapsulated poly (lactic-co-glycolic acid) microsphere ([email protected]), and its particle size, morphology, storage stability and in vitro release profile were firstly investigated. The elevation of endogenous H2S level of [email protected] was then calculated, and the pharmacodynamic study (anti-inflammation and analgesic effects) of [email protected] , SPRC, and KETO towards adjuvant induced arthritis (AIA) in rats were also studied. Finally, to test the potential side effect, the heart, liver, spleen, lung, kidney, stomach, small intestine, and large intestine were resected from rats and examined by H&E staining. Results: A monodispersed [email protected] could be observed under the SEM, and particle size was calculated around 25.12 μm. The loading efficiency (LE) for SPRC and KETO were 6.67% and 2.64%, respectively, while the encapsulation efficiency (EE) for SPRC and KETO were 37.20% and 68.28%, respectively. [email protected] showed a sustained release of SPRC and KETO in vitro, which was up-to 15 days. [email protected] could achieve a long-term elevation of the H2S concentration in vivo, while SPRC showed an instant H2S elevation and metabolize within 6 h. Interestingly, the KETO did not show any influence on the H2S concentration in vivo. After establishment of AIA model, neither SPRC nor KETO showed scarcely anti-inflammation and anti-nociception effect, while conversely, [email protected] showed an obvious mitigation towards paw edema and pain in AIA rats, which indicated an improved anti-inflammation and anti-nociception effect when co-delivery of SRC and KETO. Besides, low stimulation towards major organs in rats observed in any experimental group. Conclusion: A monodispersed was successfully prepared in this study, and [email protected] showed a sustained SPRC and KETO release in vitro and H2S release in vivo. In the pharmacodynamics study, [email protected] not only exhibited an excellent anti-inflammation and analgesic effects in AIA rats but also showed low stimulation towards rats. [ABSTRACT FROM AUTHOR]

Antibiotics are usually used for the treatment of bacterial infections, but multidrug-resistant strains are a phenomenon that has been growing at an increasing rate worldwide. Thus, there is an increasing need for novel strategies for combatting infectious diseases. Many pathogenic bacteria apply quorum sensing (QS) to regulate their pathogenicity and virulence factors production. This circuit makes the QS system an attractive target for antibacterial therapy. In the present study, an important member of non-steroidal anti-inflammatory drugs (NSAIDs), by reducing the biofilm and producing QS-regulated virulence factors, ketoprofen and its synthetic derivatives were screened against the Pseudomonas aeruginosa PAO1. All compounds showed anti-biofilm activity (16–79%) and most of them presented anti-virulence activity. In the co-treatment of ketoprofen, G20, G21, or G77 with tobramycin, biofilm is significantly reduced (potentiated to > 50%) in the number of cells protected inside the impermeable matrix. The in silico studies in addition to the similarities between the chemical structures of PqsR natural ligands and ketoprofen derivatives reinforce the possibility that the mechanism of action is through PqsR inhibition. Based on the results, the anti-pathogenic effect was more appreciable in ketoprofen, G77, and G20. [ABSTRACT FROM AUTHOR]

Chitosan/polyaniline nanofibers (CH/PANI) were prepared by an in situ oxidative polymerization of aniline in the presence of CH solution. An attractive development of nanofibers network provides free volume space for the easy encapsulation of drugs in the three-dimensional network structure. The CH/PANI hybrid was characterized by using Fourier transform infrared spectroscopy, scanning electron microscopy and X-ray diffractometry. Ketoprofen (KP), a model drug that contains a carboxylic group and a hydrophobic moiety, was loaded into CH/PANI hybrid. The release of KP from the hybrid was recorded in aqueous buffer solutions of pH 2, 6.7 and 7.4 simulating the case of oral administration. The release rate was found to be changing with the pH of the medium. The kinetics of the drug delivery system have been systematically studied by different models, which are commonly used, such as zero order, first order, Hixson–Crowell, Higuchi and Korsmeyer–Peppas models. The mechanism of release of the drug was found to follow the anomalous non-Fickian diffusion. [ABSTRACT FROM AUTHOR]

The solvent effects on C=O stretching vibrational frequency, ν(C=O), of ketoprofen (KETO) were studied experimentally using attenuated total reflection infrared spectroscopy (ATR-IR). The experimental ν(C=O) of KETO were correlated with empirical solvent parameters, including the Kirkwood–Bauer–Magat (KBM) equation, the acceptor numbers (ANs) of the solvents, the Swain equation, linear solvation energy relationships (LSERs), and the quadratic equation (QE). The solvent-induced ν(C=O) shifts of KETO displayed a better correlation with the LSER equation than with the KBM equation, ANs of the solvents, and the Swain equation. The linear effect of the solvent hydrogen-bond donor acidity (Aj) on ν(C=O) of KETO was found to be highly significant, whereas the hydrogen-bond acceptor basicity (Bj) and the interaction effect of Aj and Bj were not significant. It was also observed that the quadratic effects of Aj and Bj were slightly significant. Additionally, the linear effect of LSER parameters (π*, δ, α, and β) and the interaction effect of π*β on the ν(C=O) of KETO were highly significant. [ABSTRACT FROM AUTHOR]

Photochemical activation is proposed as a general method for controlling the crystallization of sparingly soluble carbonates in space and time. The photogeneration of carbonate in an alkaline environment is achieved upon photo‐decarboxylation of an organic precursor by using a conventional 365 nm UV LED. Local irradiation was conducted focusing the LED light on a 300 μm radius spot on a closed glass crystallization cell. The precursor solution was optimized to avoid the precipitation of the photoreaction organic byproducts and prevent photo‐induced pH changes to achieve the formation of calcium carbonate only in the corresponding irradiated area. The crystallization was monitored in real‐time by time‐lapse imaging. The method is also shown to work in gels. Similarly, it was also shown to photo‐activate locally the formation of barium carbonate biomorphs. In the last case, the morphology of these biomimetic structures was tuned by changing the irradiation intensity. [ABSTRACT FROM AUTHOR]

Introduction: Ketoprofen is a commonly used nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Side effects of ketoprofen occur mainly from the gastrointestinal tract due to the inhibition of cyclooxygenaze-1. Binge drinking at least once a week is reported by 80 million Europeans. On the day after many of them use NSAIDs. This increases the risk for damage of gastric mucosa. Aim: The aim of the study was to check if use of ketoprofen lysine salt (KLS) has any gastroprotective effect on mucosa of rat stomach after ethyl alcohol intoxication. Materials and methods: There were 6 groups of 6 male rats which received: 1. ethanol; 2. 0.9% NaCl; 3. 0.9% NaCl and ketoprofen; 4. ethanol and ketoprofen; 5. 0.9% NaCl and KLS; 6. ethanol and KLS. Results: In groups 1, 2 and 3 the histopathologic examination of the stomachs revealed normal picture, without signs of inflammation. In the group 4, 5 and 6 within the mucosa and submucosa there were visible numerous infiltrates of inflammatory cells, consisting mainly of lymphocytes, plasmocytes and eosinophilia. Total leukocyte count was elevated in group 3, 4, 6. There was a significant decrease of blood urea concentration in group 6 vs 2 and significant decrease of serum albumin in group 6 vs 1 and 2, and total protein vs group 1. Conclusion: Side effects of ketoprofen occur mainly from the gastrointestinal tract. KLS has no gastroprotective effect after ethanol-gastric injury and does not protect gastric mucosa from damage produced by binge drinking. Therefore it should not be used after drinking distilled spirits.

Ketoprofen (KTF) is often used in hospital wards, especially in its intravenous form. According to the literature review, the compatibility of ketoprofen with parenteral nutrition (PN) admixtures has not yet been investigated. For this reason, we aimed to provide data contributing to physical compatibility to ensure the safe co-administration of these medications. In this study, we examined the compatibility of KTF with eight selected commercial PN admixtures intended for central (Lipoflex Special, Omegaflex Special, Kabiven, SmofKabiven) and peripheral (Lipoflex peri, Omegaflex peri, Kabiven Peripheral, Olimel Peri N4E) administration. The KTF solution for infusion was combined in three different volume ratios with studied PN admixtures reflecting the conditions in clinical practice. The evaluation of undesirable physical destabilization of oil-in-water system or precipitate formation involved the visual inspection and the determination of mean droplet diameter, zeta potential, pH, and turbidity changes. The results of compatibility of KTF with eight commercial PN admixtures showed that three of them: Kabiven, SmofKabiven, and Kabiven Peripheral, are incompatible with KTF and should not be concomitantly administered.

Introduction: Ketoprofen (K) was synthesized in 1968. K belongs to nonsteroidal anti-inflammatory drugs (NSAIDs) and has analgesic, anti-inflammatory and antipyretic properties. K is commonly used due to rapid absorption, simple metabolism, high antinociceptive activity and fast blood brain barrier crossing. However, this substance causes various side effects which are the major factors affecting its’ popularity. Many researchers have modified this drug to discover an improved and safe NSAID. Aim: The aim of the review was to find in recent publications data bout future prospects of K of improved safety for the gastric mucosa after oral administration. Method: Systematic literature review was conducted in March 2021 (2015 onwards). We selected 22 articles from PubMed, Google Scholar, Medline Complete databases. Results and discussion: Many studies aimed at obtaining K with lower ulcerogenic properties. This article describes K with lysine, new K delivery systems, K in form of hydrogels, prodrugs and codrugs of K, K as ATB-352, K with zinc, K encapsulated as proliposomal powders and several substances that reduce the gastric side effects of K described after 2015. Conclusion: Our review confirms that modifications of K maintain its’ desirable actions and decrease ulcer producing side effect. Some new forms of K were also found to have better activity profile compared to the parent drug.

As validation is an integral part of current good manufacturing practice, nowadays, it is practiced in all pharmaceutical industries to assure that the manufacturing process is in control and products of high quality are obtained. Building of quality needs attention in the manufacturing process, from the raw materials to finalized product. The current research work is to perform prospective process validation for the manufacture of ketoprofen fast dissolving tablets (FDT) of 50 mg dose. Various trials and challenge studies were done to finalize critical process parameters. Three consecutive batches of ketoprofen FDT with the same batch size, procedure, equipment, and validation criteria were done and critical process parameters were monitored in each stage such as sifting, mixing, and compression. In-process quality control tests were performed for each batch. Friability, disintegration, dissolution, uniformity of dispersion, and assay were the major evaluation parameters considered. An average disintegration time was found to be 18-19 s and 97% of dissolution within 30 min, drug content ranging from 98.4% to 99.5% was achieved. All results complied with acceptance criteria. Evaluation results of all three batches were within acceptance criteria. The results concluded that current process validation was reproducible meeting all predetermined process variables. [ABSTRACT FROM AUTHOR]

Background: The reason why patients photosensitized to the drug ketoprofen (KP) may develop severe photoallergic skin reactions to octocrylene (OCT), an organic ultraviolet filter in sunscreens and cosmetics, remains largely unknown. OCT can be synthesized by using unsubstituted benzophenone (BP), a possible human carcinogen. Objectives: To verify if, and to what extent, BP residues are present in OCT‐containing consumer products. Methods: The raw material of OCT and 39 skincare products, of which 28 contain OCT, were chemically analysed for the presence of BP by means of liquid chromatography. Results: In the OCT raw material and in all 28 OCT‐containing products the presence of BP could be demonstrated, mostly in concentrations above 10 ppm (0.001%), whereas a majority of OCT‐free products (8/11, 73%) did not contain BP. Moreover, BP concentrations significantly increased, in a time‐ and temperature‐dependent manner, likely due to the additional degradation of OCT. Conclusions: Photoallergic contact dermatitis from OCT in patients photosensitized to KP might rely on residual BP impurities. Toxicological and ecological studies that evaluate the safety of OCT might also need to consider the concomitant presence of BP. [ABSTRACT FROM AUTHOR]

Cytokines exert biological function through signal transducer and activator of transcription factors. Prostaglandins have function as promotors, where play a key role in generation of the inflammatory response and as ones that solve inflammatory process. Non-steroidal anti-inflammatory drugs, inhibit prostaglandin synthesis but the existence of additional mechanisms is present. Thus, we aimed to explore effects of topically applied NSAIDs on the levels of PGE2 and Stat3 in the setting of two in vivo induced acute inflammation models. Male Wistar rats were randomized into five equal groups: 4 treated and a control group. Diclofenac or ketoprofen patches were applied in two different doses, i.e. equivalent to human therapeutic dose, and three times higher dose. Three hours later either model of inflammation (with 20% yeast, or with 1% carrageenan) was induced. Blood samples were taken 3 hours after and concentration levels of PGE 2 and Stat3 were determined using ELISA. Body temperature was measured at 0. 1st, 3rd and 5th hour after inflammation induction and presented in Celsius degrees. Shapiro-Wilk, Leven's, Welch's One-Way ANOVA, Kruskal-Wallis test and adjustment by Bonferroni correction were applied. In both inflammation models, no differences in the mean values of PGE 2 between control, low and high dose groups treated by either diclofenac or ketoprofen were found. In yeast inflammation, the mean value of Stat3 was significantly higher in both dose ketoprofen groups compared to control group. After ketoprofen application, no significant differences in body temperature between groups at hour 0 and 5 in either model of inflammation induced, while at 1st hour after carrageenan inflammation, significant differences were found with significantly higher values in low dose ketoprofen group compared to control group. In yeast application, significant differences in body temperature were found at hour 3 after inducing inflammation and post hoc pairwise comparison test revealed significant higher values in low dose ketoprofen group compared to control. Elevated Stat3 values post ketoprofen application in yeast model of induced inflammation were detected. Further investigation of cytokine microenvironment as well as the mechanisms of ketoprofen influence on inflammation are needed. [ABSTRACT FROM AUTHOR]

In order to minimize gastrointestinal irritation and to extend the absorption of ketoprofen, microparticles prepared with chitosan have been developed. In this study, chitosan type and drug-chitosan ratio were investigated to prepare microparticles of ketoprofen and evaluated for physical characteristics and drug release profiles. Microparticles were prepared by using ionic gelation methods with chitosan, which has two different viscosities i.e., 19 and 50 cPs, cross-linked with tripolyphosphate, and dried by spray drying method. The microparticles were made with a drug-chitosan ratio of 5:15 and 6:15. The results showed that the microparticles had spherical shapes. Increasing the amount of ketoprofen improved the drug content and entrapment efficiency. Evaluation of drug release in simulated intestinal fluid (pH 6.8) showed that the microparticles prepared with chitosan 19 cPs had the slowest release rate than those of chitosan 50 cPs, while that of the microparticles prepared with chitosan 50 cPs with the ratio of drug/polymer 6:15 was the fastest, as shown by its slope value. The release rate of microparticles with chitosan 19 cPs was slower than those microparticles with chitosan 50 cPs. It could be suggested that by increasing the amount of ketoprofen, it improved the entrapment efficiency and the release rate of microparticles. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Patients with rheumatoid arthritis (RA) or other rheumatic diseases say that pain and stiffness are symptoms affecting their quality of life. Ketoprofen and ibuprofen are the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs) to reduce inflammation and manage mild-to-moderate pain. The aim of this new systematic review of the literature and meta-analysis of randomized controlled trials (RCTs) was to compare the clinical efficacy of ketoprofen and ibuprofen in patients with RA. Methods: The MEDLINE and EMBASE scientific databases were systematically searched from their inception to November 2020 to identify RCTs directly comparing the recommended therapeutic doses of oral ketoprofen (50–200 mg/day) with ibuprofen (600–1800 mg/day) for RA pain relief. The meta-analysis was made using the standardized mean differences (SMD) of each of the identified RCTs using a fixed effects model. Results: Four RCTs involving 456 patients met the inclusion criteria. The results of the meta-analysis showed a statistically significant difference in efficacy in favor of ketoprofen (0.33, 95% CI 0.14–0.52, p = 0.0005) at all point-estimates of the mean-weighted size effect. The heterogeneity test for the efficacy outcome (the hypothesis was χ2 = 3.57%, df = 3, p value = 0.31 and the chance of a test effect was 3.49, p = 0.0005) was not significant, and this was confirmed by a Higgins percentage of 16%. The studies included in the meta-analysis did not reveal any significant differences between the two drugs in terms of tolerability or safety. Conclusions: The result of this meta-analysis shows that ketoprofen is more effective than ibuprofen in managing RA pain at therapeutic doses, thus supporting its use in clinical practice. [ABSTRACT FROM AUTHOR]

Reports on lanthanide complexes derived from non-steroidal anti-inflammatory drug molecules are still quite scarce in the literature, despite the potential properties of these molecules as therapeutic agents and biological markers. The current literature reports only lanthanide compounds containing the ketoprofenate ligand, most of the time containing coordination water molecules, which causes serious luminescence suppression. This study reports three new classes of highly photoluminescent lanthanide ketoprofenates with general formulas [Ln 2 (keto) 6 (bpy) 2 ] (1) – (3) , [Ln 2 (keto) 6 (phen) 2 ] (4) – (6) and [Ln 2 (keto) 6 (4,4′-dmbpy) 2 ] (7) – (9) (where: Ln = Eu3+, Gd3+ e Tb3+; keto = ketoprofenate anion, bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline and 4,4′-dmbpy = 4,4′-dimethyl-2,2′-bipyridine). These nine complexes were fully characterized and the photophysical studies were carried out in detail. Furthermore, the energy transfer mechanism was completely elucidated with the aid of theoretical calculations using the Sparkle/RM1 method, closely related to the nature of the employed ancillary ligand. The calculated luminescence spectroscopic parameters are in excellent agreement with those obtained experimentally, reinforcing the homobimetallic structure for these complexes. With the highest values of quantum efficiencies (%η) ever reported for lanthanide ketoprofenates, these compounds comprise potential molecules for use as biological markers or anti-inflammatory agents. [Display omitted] • Nine new Ln3+-ketoprofen complexes were synthesized and fully characterized. • Investigate the influence of the N,N-donors ligands in the photoluminescence. • The RM1 model was used to obtain the molecular structures of the Eu3+ complexes. • The intramolecular energy transfer is responsible by high quantum efficiency (η). • These complexes are potential candidates to act as biomarkers. [ABSTRACT FROM AUTHOR]

Indirect photolysis induced by naturally occurring sensitizers constitutes an important pathway accounting for the transformation and fate of many recalcitrant micropollutants in sunlit surface waters. However, the photochemical transformation of micropollutants by photosensitizing pharmaceuticals has been less investigated. In this study, we demonstrated that the non-steroidal anti-inflammatory drug ketoprofen (KTF) and its photoproducts, 3-acetylbenzophenone (AcBP) and 3-ethylbenzophenone (EtBP), could sensitize the photodegradation of coexisting sulfonamide antibiotics, e.g., sulfamethoxazole (SMX), under artificial 365 nm ultraviolet (UV) and sunlight irradiation. Key reactive species including triplet excited state and singlet oxygen (1O 2) responsible for photosensitization were identified by laser flash photolysis (LFP) and electron paramagnetic resonance (EPR) techniques, respectively. High-resolution mass spectrometry (HRMS) and structure-related reactivity analyses revealed that the sensitized photolysis of SMX occurred mainly through single electron transfer. The rate constants of sulfonamides sensitized by AcBP photolysis followed the order of sulfisoxazole (SIX)＞sulfathiazole (STZ)＞SMX＞sulfamethizole (SMT). Exposure to sunlight also enhanced the photolysis of SMX in the presence of KTF or AcBP, and water matrix had limited impact on such process. Overall, our results reveal the feasibility and mechanistic aspects of photosensitization of coexisting contaminants by pharmaceuticals (or their photoproducts) and provide new insights into the cocktail effects of pharmaceutical mixtures on their photochemical behaviors in aqueous environment. [Display omitted] • KTF photoproducts sensitized the photolysis of coexisting sulfonamide antibiotics. • Triplet excited state and 1O 2 were involved in the photosensitization. • Sensitized photolysis of SMX occurred mainly through single electron transfer. • Photosensitization efficiency of sulfonamides was structure-dependent. • Deaerated condition favored the sensitized photolysis of sulfonamides. [ABSTRACT FROM AUTHOR]

The loss of β-cell function and β-cell death are key features of diabetes. A range of mechanisms are thought to contribute to β-cell loss, including islet amyloid formation by the neuropancreatic hormone amylin (islet amyloid polypeptide, IAPP). Islet amyloid deposition also contributes to the failure of islet transplants. There are no therapeutic strategies for the treatment or prevention of islet amyloidosis. Aspirin and the nonsteroid anti-inflammatory drug (NSAID) ketoprofen, at clinically relevant doses, have been proposed to inhibit amyloid formation by amylin and thus may hold promise for treatment of islet amyloidosis. These compounds are potentially attractive given the importance of inflammation in islet amyloidosis and given the fact that there are no anti-islet amyloid agents in the clinic. We show that aspirin, even in 20-fold excess, has no effect on the kinetics of amyloid formation by amylin as judged by thioflavin-T binding, right angle light scattering, and transmission electron microscopy, nor does it alter the morphology of resulting amyloid fibrils. Aspirin showed no ability to disaggregate preformed amylin amyloid fibrils under the conditions of these studies, 25 °C and pH 7.4. Ketoprofen is similarly ineffective at inhibiting amylin amyloid formation. The compounds do, however, interfere with circular dichroism- and Congo Red-based assays of amylin amyloid formation. This study highlights the importance of using multiple methods to follow amyloid formation when screening inhibitors.

Post-operative pain management following rumen surgery is not common practice. We examined the effect of providing the pain medication ketoprofen to dairy cattle following the first stage of a rumen cannulation surgery, which involves an incision in the body wall and exteriorizing and clamping the rumen. The results of this study provide clear evidence that the first stage of the surgery was painful and ketoprofen at the time of and 24 h following surgery, alleviated some, but not all, of the post-surgical pain. Pain mitigation should be included when performing flank surgery in cattle.

Abstract Objectives Three teenage patients developed dermatitis at the site of contact of a free‐pass wristband from an amusement park. Each had experienced dermatitis due to ketoprofen. A chemical analysis of the components of the wristband and patch testing determined that the cause of the dermatitis was benzophenone, and this reaction was considered to be due to the cross‐reaction of ketoprofen and benzophenone. Because those who are photosensitized to ketoprofen are often known to coreact with several ultraviolet absorbers, we investigated the presence of cosensitization to various ultraviolet absorbers in the three patients. We also wanted to explore the background of how photosensitization to ketoprofen can occur in such young individuals. Methods The three patients underwent patch testing and photopatch testing with various ultraviolet absorbers. We also conducted a questionnaire survey of patients using ketoprofen‐containing topical medications. Results Positive photoallergic reactions were observed only with benzophenone‐3, benzophenone‐4, and octocrylene. The frequency of positive reactions was higher than in previous studies of cases after ketoprofen sensitization. About half of patients using topical medications containing ketoprofen did not know that ketoprofen could cause photocontact dermatitis. Most patients did not know about the duration of avoidance of ultraviolet exposure. Conclusions It is possible that photocontact allergy to substituted benzophenones and octocrylene was strongly established by being sensitized twice to ketoprofen and benzophenone. Sensitization to ketoprofen sometimes occurs at a young age, probably because of insufficient communication of the risk of photosensitization.

Background. The main complaint of osteoarthritis (OA) patients is a moderate or severe pain, and the drugs most frequently used to reduce it are the non-steroidal anti-inflammatory drugs. Objective: to examine the efficiency and safety of ketoprofen gel used for the treatment of knee OA patients, and also its effect on the severity of pain and improving quality of life. Materials and methods. At the premises of Clinical Physiology and Pathology of the Musculoskeletal System Department of the State Institution “D.F. Chebotarev Institute of Gerontology of the NAMS of Ukraine”, we have conducted a pilot study, which included 23 men and women aged 50–69 years with knee osteoarthritis stage 1–2. The patients were divided into two groups: group I — 13 persons whose treatment consisted of applying a thin layer of ketoprofen on the knee joint twice a day for 10 days, and group II — 10 individuals taking placebo (vaseline oil, which didn’t contain ketoprofen and active excipients) in the form of knee applications twice a day for 10 days. The study consisted of screening, visit after 10 days of the­rapy, and visit 20 days after discontinuation of therapy. At each vi­sit, the intensity of pain and functional status of the knee joints were eva­luated using the WOMAC scale (total score, subscales of pain, stiffness, daily activity), Lequesne index, and 15-meter test. In addition, a review of the articles from the following electronic me­dical databases was conducted: PubMed, Google Scholar and the Cochrane Library; there are a large amount of publications based on the effectiveness of different forms and groups of non-steroidal anti-inflammatory drugs and their comparative analysis. Results. In the group of patients who received ketoprofen we have registered: the reduction in the intensity of pain, stiffness, improvement of daily activity according to the WOMAC questionnaire subscales, and decrease of the time of the 15-meter test performance. Conclusions. Thus, ketoprofen was found to be an effective and safe agent for the local therapy of knee OA.

Abstract Background This study aimed to evaluate the safety and efficacy of reduced-dosage ketoprofen with or without tramadol in dogs. Five healthy dogs receiving standard-dosage ketoprofen (2 mg/kg SC, then 1 mg/kg PO daily) comprised Group A. Twenty dogs with osteoarthritis were randomized to receive reduced-dosage ketoprofen (0.5 mg/kg SC once; 0.25 mg/kg PO daily) alone (Group B) or in combination with tramadol (5 mg/kg/day PO) (Group C). Treatments were administered for 28 days. Platelet aggregation time (PAT), gastrointestinal (GI) endoscopy and glomerular filtration rate (GFR) were performed up to 60 days after treatment initiation. Pain was scored using a validated clinical metrology instrument up to D120. Data were analyzed with general linear mixed model for repeated measures (α = 0.05). Results PAT was not different between groups but was increased with time for all groups. GI lesion scores were higher in Group A than Groups B and C (day 28; P = 0.005) and were increased with time for Group A (P = 0.005). GFR was lower in Group A than Groups B and C (day 28; P

Introduction. The fixed combination of ketoprofen, methyl salicylate and levomenthol in the form of a cream-gel is rational. Ketoprofen forms salts with bases and esters with substances containing hydroxyl groups. Ketoprofen is practically insoluble in water, and the solubility of ketoprofen salts is much higher; this can lead to its different localization in the o/w emulsion and affect the profile of ketoprofen impurities resulting from esterification.Aim. The aim of the work is to study the effect of ketoprofen distribution in cream-gels on the formation of the impurities during storage.Materials and methods. Cream-gels with pH of 5,5 or 6,8 containing ketoprofen 2,5%, levomenthol 5% and methyl salicylate 10% have been studied. For their production, ketoprofen was dissolved in the mixture of levomenthol – methyl salicylate or in the mixed solvent of water – propylene glycol (PG) – diethylene glycol monoethyl ether (DGME). The impurities have been identified by liquid chromatography and the distribution of ketoprofen between the phases of the emulsion and the content of impurities in cream-gels have been determined by the same method. The rheological characteristics of cream-gels have been studied by viscosity-rotating viscometer method, and their microstructure – by optical microscopy.Results and their discussion. The formation of ketoprofen esters with PG, DGME and levomenthol in cream-gels have been studied. Differences in the localization of ketoprofen in the phases of the o/w emulsion at pH 5,5 and 6,8 have been shown. The formed impurities have been identified by the retention times of their peaks on chromatograms, by UV spectra and mass spectra. It has been established that during storage the content of ketoprofen esters with PG, DGME and levomenthol increased, but their formation rate was lower at pH=6,8 as well as at the adding of ketoprofen as a salt with trometamol into the dispersion medium of cream-gel. However, this resulted in formation of three impurities that were identified by UV spectra as decomposition products of methyl salicylate. When storing cream-gels with pH=6,8, the content of decomposition products of methyl salicylate, which were not detected at pH=5,5, increased.Conclusion. When making a cream-gel, ketoprofen is advisable to dissolve in a mixture of methyl salicylate and levomenthol and standardize the pH about 5,5. It is rational to use hydrophilic solvents without hydroxyl groups as penetration enhancers and the impurity profile could be limited to the menthol esters of the enantiomers of ketoprofen as a result.

The influence of chiral excipient D-chitosan (CS) on the stereoselective release of racemic ketoprofen (rac-KET) microspheres has been investigated in comparison to those microspheres containing individual enantiomers in vitro and in vivo. Stereoselectivity was observed in vitro release test, with R-KET release slightly higher than that of S-KET, especially in 3% rac-KET loading microspheres. Stereoselectivity is dependent on the content of chiral excipient and pH of release medium. A molecular docking study between CS and KET enantiomers further revealed that S-KET has a stronger interaction with CS compared to R-KET. Moreover, the plasma concentration of KET enantiomers in rats shows substantial differences, as the plasma levels of S-KET were higher than those of R-KET. Plasma levels of enantiomers from the R-KET microspheres had similar stereoselectivity as rac-KET microspheres. The S/R ratio of rac-KET microspheres was significantly lower than that of rac-KET suspension (regular-release formulation) (p

The mesoporous silica particles were prepared by the sol–gel method in one-step synthesis, in acidic conditions, from tetraethoxysilane (TEOS) and methyltriethoxysilane (MTES), varying the mole ratio of the silica precursors. Nitric acid was used as catalyst at room temperature and hexadecyltrimethyl ammonium bromide (CTAB) as structure directing agent. Optical properties, porosity and microstructure of the materials in function of the MTES/TEOS ratio were evaluated using infrared spectroscopy, nitrogen adsorption and small angle X-ray scattering. All materials showed the ordered pore structure and the high specific surfaces, making them suitable as the drug delivery systems. Drug loading and release tests using ketoprofen were performed to assess their performance for drug delivery applications. The amount of the methylated precursor used in the synthesis had little effect on the drug loading capacity, but had a strong influence on the initial rate of the drug release.

Ketoprofen is a medicinal substance that has not lost its relevance in modern medicine and pharmacy. The article describes the aspects of its application. The prospects of creating new dosage forms containing ketoprofen are considered. The possibility of creating effervescent dosage forms containing solid dispersions of ketoprofen is described.

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.

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.

The study was aimed at increasing solubility and dissolution rate of ketoprofen by using multicomponent crystallization approach with nicotinamide as additional material. The multicomponent crystallization was carried out by solvent evaporation method using 2-propanol as solvent. The solubility and dissolution test showed that the ketoprofen-nicotinamide multicomponent crystal has solubility and dissolution rate significantly higher than the solubility and dissolution rate of the pure ketoprofen.