Search

Launaea fragilis (Asso) Pau is a Cholistan desert medicinal plant. Launaea species are used as traditional remedies against various inflammatory conditions. The current research was designed to evaluate the anti-nociceptive, anti-inflammatory, and anti-arthritic potential of ethanolic extract of L. fragilis (Et-LF). The plant extract was prepared by triple maceration. GC–MS screening explored the presence of various bioactive phytoconstituents including n-tetracosanol-1, 1-heptacosanol, and n-hexadecanoic acid. DPPH assay demonstrated the antioxidant potential of Et-LF. Safety profile data indicated that Et-LF was safe up to the oral dose of 5000 mg/kg in female rats. Anti-nociceptive activity of Et-LF was assessed in hot plate method and acetic acid-induced writhing model and the results suggested that Et-LF had significant analgesic effects in both animal models. Carrageenan, histamine, and serotonin-induced edema models were used to estimate the anti-inflammatory effects of Et-LF and were found to prevent paw edema development dose dependently. The anti-arthritic effect of Et-LF was estimated in CFA-induced arthritic rat model. Treatment with Et-LF 125, 250, 500 and flurbiprofen (FP) 10 mg/kg/day significantly attenuated the paw edema, reversed the reduced body weight, and restored the altered hematological parameters in arthritic rats. Gene expression studies revealed the significant downregulation of IL-1β, TNF-α, IL-6, NF‑κB, and COX-2, and upregulation of IL-4 and IL-10 in arthritic rats treated with various doses of plant extract. Histological evaluation of ankle joints showed that Et-LF mitigated pannus formation, infiltration of inflammatory cells, and fibrous connective tissue formation in the diseased rats. Thereof, it may be concluded that the recent study demonstrated the anti-nociceptive, anti-inflammatory, and anti-arthritic effects ascribed to the signifying presence of phytoconstituents in L. fragilis. [ABSTRACT FROM AUTHOR]

Acute postoperative pain is commonly treated with flurbiprofen (FBP), but conventional delivery methods are suboptimal. This study prepared a new non-burst release microneedles (MNs) using genipin cross-linked gelatin (cGel). By adding varying amounts of genipin to modulate the crosslinking degree of cGel, the drug release behavior of the drug-loaded MNs in the skin can be altered. The crosslinking parameters that meet therapeutic requirements are selected, thus providing rapid and long-lasting analgesic effects. cGel solutions were successfully cross-linked, altering matrix material microstructure, confirmed by scanning electron microscope imaging and fourier transform infrared spectroscopy. MNs demonstrated increasing mechanical strength with higher crosslinking. Drug release rates were rapid initially, then slowed, exhibiting a characteristic of decreased release rates with increasing degrees of crosslinking. In vivo, FBP/cGel MNs significantly reduced allodynia and hyperalgesia post-surgery, with the greatest effect observed at 2–3 h post-surgery, and can maintain analgesia for up to 6 h. Biosafety tests confirmed good biocompatibility. FBP/cGel MNs effectively penetrate the stratum corneum, safely delivering drugs with significant analgesic effects, excellent mechanical properties, and good biocompatibility, representing a promising strategy for managing acute postoperative pain. [ABSTRACT FROM AUTHOR]

The pharmaceutical industry faces a significant challenge from the low water solubility of nearly 90% of newly developed Active Pharmaceutical Ingredients (APIs). Despite extensive efforts to improve solubility, approximately 40% of these APIs encounter commercialization hurdles, impacting drug efficacy. In this context, a promising strategy will be introduced in which nanosuspensions, particularly polyvinyl alcohol (PVA) as a stabilizer, are applied to increase drug solubility. In this work using molecular dynamics simulations, the nanosuspension of four poorly water-soluble drugs (flurbiprofen, bezafibrate, miconazole, and phenytoin) stabilized with PVA is investigated. The simulation data showed van der Waals energies between polyvinyl alcohol with flurbiprofen and bezafibrate are − 101.12 and − 58.42 kJ/mol, respectively. The results indicate that PVA is an effective stabilizer for these drugs, and superior interactions are obtained with flurbiprofen and bezafibrate. The study also explores the impact of PVA on water molecule diffusion, providing insights into the stability of nanosuspensions. Obtained results also provide valuable insights into hydrogen bond formation, diffusion coefficients, and nanosuspension stability, contributing to the rational design and optimization of pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

This study presents the enantiomeric resolution of three profen drugs, viz., flurbiprofen (FLB), fenoprofen, and zaltoprofen by employing sitafloxacin (SIT) as a chiral selector within a direct thin-layer chromatography (TLC) method. Chromatographic resolution of three drugs was carried out using a mobile phase consisting of acetonitrile‒methanol‒trimethylamine (6:3:1, V/V, pH 8.5), with a stationary phase maintained at pH 5. Analytical validation of the FLB enantiomeric resolution exhibited consistent recovery rates, with coefficient of variation (%CV) values consistently below 2%. Furthermore, the method demonstrated sensitivity, with low limits of detection and quantification values of 0.058 and 0.172 µg per spot, respectively, for FLB enantiomers, indicating reliable detection at low concentrations. The analytical data validate the effectiveness and reliability of the developed TLC method for the enantiomeric resolution of profen drugs, offering significant implications for pharmaceutical research and development. [ABSTRACT FROM AUTHOR]

Introduction: PDX-02 (Flurbiprofen sodium) is a topical nonsteroidal anti-inflammatory drug in gel formulation for local analgesia and anti-inflammation. A Phase I clinical trial was conducted to assess the safety, tolerability, and pharmacokinetics of single and multiple doses of PDX-02 gel in Chinese healthy adults. Methods: The trial comprised three parts: (1) a single-dose ascending study with three dose levels (0.5%, 1% to 2% PDX-02 gel) applied on a 136 cm2 skin area; (2) a multiple-dose study with either 1% or 2% PDX-02 gel applied on a 136 cm2 skin area for 7 consecutive days; and (3) a high dose group with 2% PDX-02 gel on an 816 cm2 skin area and a frequent multiple dose group with 2% PDX-02 gel on a 272 cm2 skin area four times a day for 7 consecutive days. The safety, tolerability and pharmacokinetics of the PDX-02 gel were evaluated in each part. Results: A total of sixty participants completed the trial, with all adverse events recovered and all positive skin reaction being transient and recovered. The overall absorption of topical PDX-02 gel was slow with a mean peak time exceeding 9 h. The elimination rate remained consistent between dose groups. A less-than-dose-proportional nonlinear pharmacokinetics relationship was observed within the studied dose range, and this is likely due to the autoinduction of skin first-pass metabolism. Conclusion: The topical PDX-02 gel showed favorable safety and tolerability in both single and multiple dosing studies, with a less-than-dose-proportional nonlinear pharmacokinetics observed. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are an important class of anti-inflammatory drugs widely used for the treatment of musculoskeletal disorders, mild-to-moderate pain, and fever. This review aimed to explain the functional role and possible mechanisms of the antifungal effects of NSAIDs alone or in combination with antifungal drugs in vitro and in vivo. Several studies reported that NSAIDs such as aspirin, ibuprofen, diclofenac, indomethacin, ketorolac, celecoxib, flurbiprofen, and nimesulide had antifungal activities in vitro, either fungistatic or fungicidal, against different strains of Candida, Aspergillus, Cryptococcus, Microsporum, and Trichophyton species. These drugs inhibited biofilm adhesion and development, and yeast-to-hypha conversion which may be related to a prostaglandin E2 (PGE2)/PGEx-dependent mechanism. Modulating PGE2 levels by NSAIDs during fungal infection can be introduced as a possible mechanism to overcome. In addition, some important mechanisms of the antifungal activities of NSAIDs and their new derivatives on fungi and host immune responses are summarized. Overall, we believe that using NSAIDs along with classical antifungal drugs has the potential to be investigated as a novel therapeutic strategy in clinical studies. Furthermore, combination therapy can help manage resistant strains, increase the efficacy of antifungal drugs, and reduce toxicity. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the present work was to develop levofloxacin-flurbiprofen coloaded PLGA (LEV-FLU-PLGA) nanoparticles with surface modification using chitosan to attain mucoadhesion for the treatment of bacterial conjunctivitis. Method: Polymeric nanoparticles were prepared by nanoprecipitation method and evaluated for parameters like particle size, PDI, zeta potential, entrapment efficiency (%), in vitro drug release, ex vivo permeation studies, microbial assay against Staphylococcus aureus and ocular tolerance using Hen's egg test-chorioallantoic membrane (HET-CAM). Furthermore, surface of optimized PLGA nanoparticle formulation was modified by coating with chitosan. Results: LEV-FLU-PLGA nanoparticles demonstrated particle size of 166.1 nm with PDI of 0.137 and zeta potential of − 16.8 mV. The entrapment efficiency was found to be 39.37% for levofloxacin (LEV) and 48.33% for flurbiprofen (FLU), whereas for surface-modified nanoparticles, it was found to be 42.05% for LEV and 45.26% for FLU. LEV-FLU chitosan-coated PLGA nanoparticles showed an increase in particle size, i.e., 333.6 nm with PDI of 0.319 and an inversion of zeta potential to 37.67 mV. The developed nanosystems showed sustained release and improved eye permeability. Microbiological studies showed equivalent zone of inhibition to that of marketed formulation. HET-CAM assay revealed the non-irritant nature of drug-loaded PLGA nanoparticles; however, chitosan-coated PLGA nanoparticles were found to be moderately irritating owing to the acidic nature of formulation. Conclusion: The nanoparticulate system provides prolonged drug release making it a promising alternative to conventional dosage forms. It reduces systemic effects of locally acting drugs, improving therapeutic efficacy and patient compliance. [ABSTRACT FROM AUTHOR]

Flurbiprofen derivatives 1–18 were screened for their free radical scavenging activities. Initially, flurbiprofen hydrazide 1 was synthesized and subjected to various chemical transformations to obtain a range of flurbiprofen hydrazide analogs 2–9 and flurbiprofen–oxadiazole analogs 10–18. All compounds 1–18 showed good DPPH (IC50 = 0.60±0.16 to 1.77±0.04 µM) and ABTS (IC50 = 0.40±0.10 to 1.46±0.06 µM) radical scavenging activities as compared to the standard ascorbic acid (IC50 = 0.51±0.18 µM for both DPPH and ABTS). Among the synthesized derivatives, compound 13 (DPPH, IC50 = 0.40±0.10 µM; ABTS, IC50 = 0.60±0.16 µM) was found to be the most active. The remaining compounds displayed good to moderate radical scavenging activities. These active compounds can serve as lead molecules to identify more powerful antioxidant agents. [ABSTRACT FROM AUTHOR]

Purpose: Mesenteric traction syndrome (MTS) sometimes occurs during abdominal surgery. Prophylactic administration of flurbiprofen, a non-steroidal anti-inflammatory drug, prevents the development of MTS. However, administration of non-steroidal anti-inflammatory drugs for postoperative pain increases the incidence of postoperative bleeding. Our aim was to examine the effect of prophylactic flurbiprofen administration on postoperative leakage or bleeding after gastrointestinal surgery. Methods: A retrospective observational study on patients who underwent open or laparoscopic abdominal surgery was conducted. Perioperative, anesthesia and medical records were reviewed. Patients who did (Flurbio-Group) or did not receive (Control-Group) prophylactic flurbiprofen administration were compared. Then, the Flurbio-Group and Control-Group were each divided into two groups according to whether the patients did or did not develop MTS (Flurbio-MTS-Group and Flurbio-no-MTS-Group, respectively, Control-MTS-Group and Control-no-MTS-Group, respectively). Results: This study included 188 patients (Flurbio-MTS-Group, 1 patient; Flurbio-no-MTS-Group, 31 patients; Control-MTS-Group, 59 patients; Control-no-MTS-Group, 97 patients). Seventeen patients developed postoperative leakage or bleeding. Eleven Flurbio-MTS-Group patients (18.6%), 4 Flurbio-no-MTS-Group patients (12.9%, 4/31), and only 2 Control-no-MTS-Group patients (2%, 2/97) developed postoperative leakage or bleeding. Multivariate logistic regression analysis demonstrated that there was a qualitative interaction effect between prophylactic administration of flurbiprofen and the development of MTS on postoperative leakage or bleeding. Conclusion: Prophylactic flurbiprofen administration increased the risk of postoperative leakage or bleeding among patients who did not develop MTS. [ABSTRACT FROM AUTHOR]

Inflammation is the core contributor in the pathogenesis of various acute and chronic illness including appendicitis, bronchitis, arthritis, cancer and neurological diseases. NSAIDs, commonly used medications for inflammatory diseases, on prolonged use cause GI bleeding, ulcers and many more issues. Plant-based therapeutic agents including essential oils in combination with low-dose synthetic drugs have been shown to produce synergistic effects and reduce complications of synthetic drugs. This study was designed to evaluate the anti-inflammatory, analgesic and anti-pyretic properties of Eucalyptus globulus essential oil alone and in combination with flurbiprofen. GC–MS analysis was performed to screen chemical composition of oil. In vitro anti-inflammatory assay (membrane stabilization assay) and in vivo inflammatory acute (carrageenan and histamine-induced paw oedema) and chronic (cotton pellet-induced granuloma and Complete Freund's adjuvant-induced arthritis) models were performed to check anti-inflammatory properties. Acetic acid-induced algesia and yeast-induced pyrexia models were performed to check analgesic and anti-pyretic properties. qRT-PCR was performed to study the effect of treatments on the expression of inflammatory biomarkers. GC–MS analysis of E. globulus essential oil showed the presence of eucalyptol along with other active biomolecules. 500 + 10 mg/kg of oil-drug combination showed significantly (p < 0.05) better in vitro membrane stabilization effects as compared with groups treated with 500 mg/kg of E. globulus oil and 10 mg/kg of Flurbiprofen alone. 500 + 10 mg/kg of oil-drug combination showed significantly (p < 0.05) better anti-inflammatory, analgesic and antipyretic effects as compared to 500 mg/kg of E. globulus oil alone in all in vivo models. When comparison was done between 500 + 10 mg/kg of oil-drug combination-treated and 10 mg/kg Flurbiprofen-treated group, the former group showed significantly (p < 0.05) better anti-inflammatory and anti-pyretic effects, but there were non-significant differences in the analgesic model. Animal group treated with 10 mg/kg of Flurbiprofen showed significantly (p < 0.05) better anti-inflammatory and analgesic effects than group treated with 500 mg/kg of oil alone while, there were non-significant differences in anti-pyretic effects. qRT-PCR analysis showed significant (p < 0.05) down-regulation in the expression of IL-4 and TNF-α in serum samples of animals treated with 500 + 10 mg/kg of oil-drug combination as compared to the diseased control (arthritic) group. Overall, the current research demonstrates that Eucalyptus globulus essential oil in combination with flurbiprofen showed better anti-inflammatory, analgesic and anti-pyretic effects than oil and flurbiprofen alone which is attributed to the down-regulation of pro-inflammatory biomarkers (IL-4 and TNF-α). Further studies are required to formulate a stable dosage form and to check the anti-inflammatory efficacy in different inflammatory disorders. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the effects of topical hyaluronic acid (HA), hypochlorous acid (HOCl), and flurbiprofen on postoperative morbidity of palatal donor sites after free gingival graft (FGG) surgery. Materials and methods: Sixty patients requiring FGG were randomly assigned into four groups: control, HA gel (600 mg/100 g high molecular weight hyaluronic acid), HOCl spray (170–200 ppm, ph7.1), flurbiprofen spray (0.075gr flurbiprofen). Topical agents were applied for 14 days, according to groups. Patients were followed for 28 days. Palatal healing was assessed with the Laundry wound healing index (WHI). Complete epithelization (CE) was evaluated with photographs and H2O2 bubbling. Pain, burning sensation, chewing efficacy, and tissue color match (CM) were evaluated using a visual analog scale (VAS). Postoperative analgesic consumption and delayed bleeding (DB) were also recorded. Results: HA provided better WHI values on the 7th, 14th, and 21st days compared to the other groups, respectively (p < 0.05). CE was formed on the 21st day in the HA group but on the 28th day in the other groups. HOCl and flurbiprofen groups were not different from the control group or each other in terms of WHI. HOCl had the lowest VAS scores of all time periods. DB was not observed in any group. Significantly fewer analgesics were taken in the topical agent-applied groups compared to the control group. Conclusions: HA exhibits a positive impact on the epithelization of palatal wound healing and color matching. HOCl and flurbiprofen provided less pain; however, they might have negative effects on palatal wound healing. Clinical relevance: As a result of obtaining free gingival grafts from palatal tissue for mucogingival surgical procedures, secondary wound healing of the donor area occurs. This wound in the palatal region can cause discomfort and pain every time patients use their mouths. The use of HA can reduce postoperative complications by accelerating wound healing and reducing pain. The topical use of flurbiprofen and HOCl can reduce patients' pain. [ABSTRACT FROM AUTHOR]

Purpose: To overcome the problems of low bioavailability of the drug associated with the short pre-corneal residence time, a thermoresponsive in situ gel system containing poloxamer P407, hydroxypropyl methylcellulose, and chitosan was developed to prolong the pre-corneal residence time of the drug. Methods: The central composite design was utilized to assess the effects of the concentration of poloxamer 407 hydroxypropyl methylcellulose and chitosan, the concentration of polymer, and the polymer type on the viscosity, pH, and gelation temperature, which were considered indicators of optimum formulations. Results: After model selection for response analysis, the quadratic model was found to be the best-fitting model for the relationship between independent factors and response variables. As a result of the central composite design, the optimized formulation contained 15.17% poloxamer 407 and 2.141% chitosan. Viscosity 25 °C = 2199.4 ± 26.2, viscosity 35 °C = 15,487.2 ± 117.4, pH = 6.5 ± 0.01, and gelation temperature °C = 33.3 ± 0.47 were obtained. The ex-vivo study revealed that the BRN formulation containing flurbiprofen-cyclodextrin inclusion complex has higher corneal penetration (P < 0.01). The cytotoxicity of ARPE-19 cells and irritation studies, as measured by in situ gel, was found to be acceptable. In lipoxygenase studies, the effectiveness of the BRN formulation was found to be significantly higher than other formulations (P < 0.01). Conclusions: It is thought that the BRN formulation may be an alternative to the treatment of ocular allergic disease. [ABSTRACT FROM AUTHOR]

In this research, FeCo2O4 nanomaterial was successfully synthesized by a typical sol–gel method and conducted as an effective agent for peroxymonosulfate (PMS) activation to eliminate antibiotics flurbiprofen (FLU), a strong nonsteroidal drug. FeCo2O4 nanomaterial was characterized by XRD, TEM, SEM, and XPS. Various characterization results proved that FeCo2O4 held stable spinel structure. The interfering factors including initial pH, PMS concentration, catalyst dosage, inorganic anions, and humic acid on FLU removal were also discussed. The conclusion was that the removal efficiency of FLU reached 98.2% within 120 min after adding FeCo2O4 (0.4 g L−1) and PMS (3 mM). The optimal pH for FLU degradation was the initial pH of 6.5; too acidic or alkaline was not conductive to the degradation. The existence of HA and Cl− restrained the degradation of FLU, and HCO3− promoted the removal, while the influence of NO3− and SO42− could not be considered. The radical scavenging experiment confirmed that •OH, O2•−, and SO4•− participated in FLU removal and SO4•− functioned a leading role. FeCo2O4 showed high efficiency for PMS activation in pH range of 3.0 to 10.0. After the fourth cycle operation, the FLU removal rate exceeded 76.9%, and the Co leaching rate was low during the catalytic reaction. This study shows that FeCo2O4 nanomaterial is an efficient and environment-friendly catalyst, which can be applied for PMS activation to remove organic pollutants in water. [ABSTRACT FROM AUTHOR]

Background: Postoperative pain control remains unsatisfactory. Patients who underwent laparotomy may have moderate to severe acute postoperative pain. Comparative cost-effectiveness of the following postoperative pain treatment options remains to be investigated: patient-controlled intravenous analgesia (PCIA) with flurbiprofen therapy, flurbiprofen monotherapy, parecoxib monotherapy, or dezocine monotherapy. Aim: To provide a cost-effectiveness analysis (CEA) of four analgesic regimens for patients with postoperative pain following laparotomy surgeries. Method: Patients with postoperative pain following laparotomy were retrospectively reviewed from a postoperative pain management database created by pharmacists, and divided into four groups according to analgesic regimens. The clinical outcomes were visual analogue scale (VAS) scores and the incidence of adverse drug events. The CEA was conducted by developing a decision tree model based on retrospective data. The maximum incremental cost-effectiveness ratio (ICER) of the four regimens was used as the willingness-to-pay (WTP) value. Meanwhile, the uncertainty of the base-case results was examined by one-way and probabilistic sensitivity analyses. Results: A total of 677 patients were included in the retrospective study. PCIA with flurbiprofen therapy had the lowest VAS scores at 6, 24, 48 h postoperatively. Based on the base-case results, PCIA plus flurbiprofen was the optimal regimen with the highest effectiveness, while flurbiprofen monotherapy had the lowest cost. PCIA plus flurbiprofen was the optimal regimen even with a WTP value of 0 dollars. Conclusion: PCIA plus flurbiprofen therapy was the optimal regimen. Parecoxib monotherapy was more cost-effective than flurbiprofen monotherapy. The findings may guide the selection of postoperative pain management. [ABSTRACT FROM AUTHOR]

A composite magnetic adsorbent was developed by embedding graphene quantum dots (GQDs), silica-modified magnetite (Fe3O4-SiO2), and mesoporous carbon (MPC) into a molecularly imprinted polymer (GQDs/Fe3O4-SiO2/MPC/MIP). The adsorbent was applied to extract nonsteroidal anti-inflammatory drugs (NSAIDs) in milk. The MIP was formed via a sol–gel copolymerization using flurbiprofen, diflunisal, and mefenamic acid as template molecules, 3-aminopropyltriethoxysilane as a monomer, and tetraethyl orthosilicate as a cross-linker. GQDs and MPC enhanced affinity binding between NSAIDs and the adsorbent through π-π stacking, hydrogen bonding, and hydrophobic interaction. The Fe3O4-SiO2 nanoparticles embedded in the composite adsorbent enabled its rapid isolation from the sample solution. The extracted NSAIDs were quantified by high-performance liquid chromatography and exhibited good linearity from 1.0 to 100.0 μg L−1 for flurbiprofen and 0.5 to 100.0 μg L−1 for diflunisal and mefenamic acid, respectively. The limits of detection ranged from 0.5 to 1.0 μg L−1. Recoveries of NSAIDs from spiked milk samples ranged from 81.4 to 93.7%, with RSDs below 7%. The reproducibility of the fabricated adsorbent was good and in the optimal conditions, the developed adsorbent could be used for up to six extraction-desorption cycles. [ABSTRACT FROM AUTHOR]

In this study, flurbiprofen (FB) was selected as the model drug, and hyaluronic acid–coated flurbiprofen-layered double hydroxide ophthalmic drug delivery system (HA-FB-LDH) was designed and prepared. In this system, the model drug flurbiprofen was intercalated in layered double hydroxide and coated with hyaluronic acid (HA), so as to prolong the corneal residence time and increase the corneal permeability of the drug. Layered double hydroxide (LDH) was prepared by alcohol-water coprecipitation method. Through single factor investigation, the optimum preparation conditions were obtained as follows: The Mg/Al ratio was 2:1, the reaction pH was 11.0, the hydrothermal reaction time was 24 h, and the hydrothermal reaction temperature was 100°C. Under these conditions, the particle size of LDH was 116.4 ± 0.8 nm, the potential was 42.2 ± 1.2 mV, and a relatively regular crystal structure could be had. Then FB was intercalated into the LDH layer to prepare flurbiprofen-layered double hydroxide (FB-LDH). In the end, HA-FB-LDH was prepared by the stirring-ultrasonic method, in which through prescription screening, the molecular weight of HA was 200–400 kDa and the concentration of HA solution was 1.25 mg·mL −1, the final particle size of HA-FB-LDH was 185.8 ± 3.3 nm, and potential of − 31.4 ± 0.7 mV. The successful loading of FB and the coating of HA were verified by XRD, FTIR, TGA, TEM, and other characterization methods. The results of in vitro stability experiment indicated that the coating of HA could significantly enhance the stability of LDH in the presence of electrolytes. The in vitro release results suggested that the cumulative release amounts of FB-LDH and HA-FB-LDH within 12 h were 92.99 ± 0.37% and 74.82 ± 0.29% respectively, showing a certain sustained release effect. At the same time, the release mechanism of FB-LDH was preliminarily explored by in vitro release experiment, which proved that the release mechanism of FB-LDH was mainly ion exchange. The results of in vivo ocular irritation experiments demonstrated that the ophthalmic preparation studied in this paper was safe and non-irritating. The results of tear pharmacokinetics in rabbits showed that the area under the curve(AUC), the average residence time (MRT), and the highest concentration (Cmax) in tears in the HA-FB-LDH group were 4.43, 4.48, and 2.27 times higher than those in eye drops group separately. Furthermore, the AUC of the HA-FB-LDH group was 1.48 times higher than that of the FB-LDH group. The above results suggested that HA-FB-LDH could improve the precorneal residence time. The results of aqueous humor pharmacokinetics in rabbits indicated that the AUC, MRT, and maximum concentration (Cmax) in aqueous humor in the HA-FB-LDH group were 6.88, 2.15, and 4.08 times of those in the eye drop group respectively. Additionally, the AUC and MRT of the HA-FB-LDH group were 1.55 and 1.63 times those of the FB-LDH group separately. These mentioned findings verified that HA-FB-LDH could enhance the corneal permeability of the drug. The fluorescent substance-fluoresce isothiocyanate (FITC) was substituted for FB intercalation in LDH for in vitro tissue imaging study of rabbits, whose results stated clearly that FITC-LDH and HA-FITC-LDH could both prolong the precorneal residence time of drugs, and HA-FITC-LDH could increase the corneal permeability of the drug to a certain extent. To sum up, HA-FB-LDH, which can overcome the shortcomings of low bioavailability of traditional eye drops to a certain degree, is a safe and effective ophthalmic drug delivery system. [ABSTRACT FROM AUTHOR]

A new simple, rapid, and sensitive spectrophotometric method for the determination of flurbiprofen in pharmaceutical preparations was developed and tested. The proposed method is based on the reaction of flurbiprofen with astraphloxine at pH 8.0 – 10.8 followed by extraction of the resulting ion associate by toluene and determination of the optical density at an absorption maximum of 563 nm [ε = 7.6 × 104 L/(mol·cm)]. The calibration curve was linear from 0.7 to 16.2 μg/mL of flurbiprofen. The detection limit was 0.037 μg/mL. [ABSTRACT FROM AUTHOR]

The aim of this study was to establish the physiologically based pharmacokinetic (PBPK) model of flurbiprofen related to CYP2C9 genetic polymorphism and describe the pharmacokinetics of flurbiprofen in different CYP2C9 genotypes. PK-Sim® software was used for the model development and validation. A total of 16 clinical pharmacokinetic data for flurbiprofen in different CYP2C9 genotypes, dose regimens, and age groups were used for the PBPK modeling. Turnover number (kcat) of CYP2C9 values were optimized to capture the observed profiles in different CYP2C9 genotypes. In the simulation, predicted fraction metabolized by CYP2C9, fraction excreted to urine, bioavailability, and volume of distribution were similar to previously reported values. Predicted plasma concentration-time profiles in different CYP2C9 genotypes were visually similar to the observed profiles. Predicted AUCinf in CYP2C9*1/*2, CYP2C9*1/*3, and CYP2C9*3/*3 genotypes were 1.44-, 2.05-, and 3.67-fold higher than the CYP2C9*1/*1 genotype. The ranges of fold errors for AUCinf, Cmax, and t1/2 were 0.84–1.00, 0.61–1.22, and 0.74–0.94 in development and 0.59–0.98, 0.52–0.97, and 0.61–1.52 in validation, respectively, which were within the acceptance criterion. Thus, the PBPK model was successfully established and described the pharmacokinetics of flurbiprofen in different CYP2C9 genotypes, dose regimens, and age groups. The present model could guide the decision-making of tailored drug administration strategy by predicting the pharmacokinetics of flurbiprofen in various clinical scenarios. [ABSTRACT FROM AUTHOR]

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) possess analgesic and anti-inflammatory properties by inhibiting cyclooxygenase (COX) enzymes. Conflicting evidence exists on whether NSAIDs influence signaling related to muscle adaptations and exercise with some research finding a reduction in muscle protein synthesis signaling via the AKT-mTOR pathway, changes in satellite cell signaling, reductions in muscle protein degradation, and reductions in cell proliferation. In this study, we determined if a single maximal dose of flurbiprofen (FLU), celecoxib (CEL), ibuprofen (IBU), or a placebo (PLA) affects the short-term muscle signaling responses to plyometric exercise.This was a block randomized, double-masked, crossover design, where 12 participants performed four plyometric exercise bouts consisting of 10 sets of 10 plyometric jumps at 40% 1RM. Two hours before exercise, participants consumed a single dose of celecoxib (CEL 200 mg), IBU (800 mg), FLU (100 mg) or PLA with food. Muscle biopsy samples were collected before and 3-h after exercise from the vastus lateralis. Data were analyzed using a repeated measures (RM) ANOVA, ANOVA, or a Friedman test. Significance was considered at p < 0.05.We found no treatment effects on the mRNA expression of PTSG1, PTSG2, MYC, TBP, RPLOP, MYOD1, Pax7, MYOG, Atrogin-1, or MURF1 (all, p > 0.05). We also found no treatment effects on AKT-mTOR signaling or MAPK signaling measured through the phosphorylation status of mTORS2441, mTORS2448, RPS6 235/236, RPS 240/244, 4EBP1, ERK1/2, p38 T180/182 normalized to their respective total abundance (all, p > 0.05). However, we did find a significant difference between MNK1 T197/202 in PLA compared to FLU (p < .05).A single, maximal dose of IBU, CEL, or FLU taken prior to exercise did not affect the signaling of muscle protein synthesis, protein degradation, or ribosome biogenesis three hours after a plyometric training bout.Methods: Non-steroidal anti-inflammatory drugs (NSAIDs) possess analgesic and anti-inflammatory properties by inhibiting cyclooxygenase (COX) enzymes. Conflicting evidence exists on whether NSAIDs influence signaling related to muscle adaptations and exercise with some research finding a reduction in muscle protein synthesis signaling via the AKT-mTOR pathway, changes in satellite cell signaling, reductions in muscle protein degradation, and reductions in cell proliferation. In this study, we determined if a single maximal dose of flurbiprofen (FLU), celecoxib (CEL), ibuprofen (IBU), or a placebo (PLA) affects the short-term muscle signaling responses to plyometric exercise.This was a block randomized, double-masked, crossover design, where 12 participants performed four plyometric exercise bouts consisting of 10 sets of 10 plyometric jumps at 40% 1RM. Two hours before exercise, participants consumed a single dose of celecoxib (CEL 200 mg), IBU (800 mg), FLU (100 mg) or PLA with food. Muscle biopsy samples were collected before and 3-h after exercise from the vastus lateralis. Data were analyzed using a repeated measures (RM) ANOVA, ANOVA, or a Friedman test. Significance was considered at p < 0.05.We found no treatment effects on the mRNA expression of PTSG1, PTSG2, MYC, TBP, RPLOP, MYOD1, Pax7, MYOG, Atrogin-1, or MURF1 (all, p > 0.05). We also found no treatment effects on AKT-mTOR signaling or MAPK signaling measured through the phosphorylation status of mTORS2441, mTORS2448, RPS6 235/236, RPS 240/244, 4EBP1, ERK1/2, p38 T180/182 normalized to their respective total abundance (all, p > 0.05). However, we did find a significant difference between MNK1 T197/202 in PLA compared to FLU (p < .05).A single, maximal dose of IBU, CEL, or FLU taken prior to exercise did not affect the signaling of muscle protein synthesis, protein degradation, or ribosome biogenesis three hours after a plyometric training bout.Results: Non-steroidal anti-inflammatory drugs (NSAIDs) possess analgesic and anti-inflammatory properties by inhibiting cyclooxygenase (COX) enzymes. Conflicting evidence exists on whether NSAIDs influence signaling related to muscle adaptations and exercise with some research finding a reduction in muscle protein synthesis signaling via the AKT-mTOR pathway, changes in satellite cell signaling, reductions in muscle protein degradation, and reductions in cell proliferation. In this study, we determined if a single maximal dose of flurbiprofen (FLU), celecoxib (CEL), ibuprofen (IBU), or a placebo (PLA) affects the short-term muscle signaling responses to plyometric exercise.This was a block randomized, double-masked, crossover design, where 12 participants performed four plyometric exercise bouts consisting of 10 sets of 10 plyometric jumps at 40% 1RM. Two hours before exercise, participants consumed a single dose of celecoxib (CEL 200 mg), IBU (800 mg), FLU (100 mg) or PLA with food. Muscle biopsy samples were collected before and 3-h after exercise from the vastus lateralis. Data were analyzed using a repeated measures (RM) ANOVA, ANOVA, or a Friedman test. Significance was considered at p < 0.05.We found no treatment effects on the mRNA expression of PTSG1, PTSG2, MYC, TBP, RPLOP, MYOD1, Pax7, MYOG, Atrogin-1, or MURF1 (all, p > 0.05). We also found no treatment effects on AKT-mTOR signaling or MAPK signaling measured through the phosphorylation status of mTORS2441, mTORS2448, RPS6 235/236, RPS 240/244, 4EBP1, ERK1/2, p38 T180/182 normalized to their respective total abundance (all, p > 0.05). However, we did find a significant difference between MNK1 T197/202 in PLA compared to FLU (p < .05).A single, maximal dose of IBU, CEL, or FLU taken prior to exercise did not affect the signaling of muscle protein synthesis, protein degradation, or ribosome biogenesis three hours after a plyometric training bout.Conclusion: Non-steroidal anti-inflammatory drugs (NSAIDs) possess analgesic and anti-inflammatory properties by inhibiting cyclooxygenase (COX) enzymes. Conflicting evidence exists on whether NSAIDs influence signaling related to muscle adaptations and exercise with some research finding a reduction in muscle protein synthesis signaling via the AKT-mTOR pathway, changes in satellite cell signaling, reductions in muscle protein degradation, and reductions in cell proliferation. In this study, we determined if a single maximal dose of flurbiprofen (FLU), celecoxib (CEL), ibuprofen (IBU), or a placebo (PLA) affects the short-term muscle signaling responses to plyometric exercise.This was a block randomized, double-masked, crossover design, where 12 participants performed four plyometric exercise bouts consisting of 10 sets of 10 plyometric jumps at 40% 1RM. Two hours before exercise, participants consumed a single dose of celecoxib (CEL 200 mg), IBU (800 mg), FLU (100 mg) or PLA with food. Muscle biopsy samples were collected before and 3-h after exercise from the vastus lateralis. Data were analyzed using a repeated measures (RM) ANOVA, ANOVA, or a Friedman test. Significance was considered at p < 0.05.We found no treatment effects on the mRNA expression of PTSG1, PTSG2, MYC, TBP, RPLOP, MYOD1, Pax7, MYOG, Atrogin-1, or MURF1 (all, p > 0.05). We also found no treatment effects on AKT-mTOR signaling or MAPK signaling measured through the phosphorylation status of mTORS2441, mTORS2448, RPS6 235/236, RPS 240/244, 4EBP1, ERK1/2, p38 T180/182 normalized to their respective total abundance (all, p > 0.05). However, we did find a significant difference between MNK1 T197/202 in PLA compared to FLU (p < .05).A single, maximal dose of IBU, CEL, or FLU taken prior to exercise did not affect the signaling of muscle protein synthesis, protein degradation, or ribosome biogenesis three hours after a plyometric training bout. [ABSTRACT FROM AUTHOR]

Flurbiprofen axetil has been proved as an alternative analgesia for postoperative pain. The aim of this study was to investigate the effects of different strategies of flurbiprofen axetil administration on postoperative pain. A total of 160 patients undergoing abdominal surgery were randomly assigned to four groups (n = 40 each): (A) 30 min before the start of surgery, the group was given 1 mg/kg flurbiprofen, then the intravenous patient-controlled analgesia (PCIA) pump contained 0.7μg/kg sufentanil, 1 mg/kg flurbiprofen axetil, 10 mg tropisetron, and 0.4 mg/kg dezocine. (B) The group received 1 mg/kg flurbiprofen axetil before surgical suture, and the PCIA pump was same as group A. (C) The group received no flurbiprofen axetil during operation, but the PCIA pump contained 1 μg/kg sufentanil, 2 mg/kg flurbiprofen axetil, 10 mg tropisetron, and 0.4 mg/kg dezocine. (D) The group was given 1 mg/kg flurbiprofen axetil at 30 min prior to the beginning of surgery and before surgical suture simultaneously, and PCIA pump was the same as group C, but flurbiprofen axetil was not used. Visual Analog Scale at rest/movement (VAS-R/M), sedation score, comfort score, and side effects were observed 48 h postoperatively. Preoperative or intraoperative intravenous flurbiprofen axetil injection decreased the VAS at 8 h, 12 h, and 24 h after surgery compared with postoperative PCIA contained flurbiprofen axetil. VAS scores at rest with intravenous flurbiprofen axetil at 30 min prior to the start of surgery were significantly decreased compared to that before surgical suture at 2 h, 8 h, and 48 h postoperatively. Flurbiprofen axetil ameliorates postoperative pain of patients with abdominal surgery, enhances analgesic effects of sufentanil, and decreases the consumption of sufentanil. [ABSTRACT FROM AUTHOR]

Understanding the drug solubility behavior is likely the first essential requirement for designing the supercritical technology for pharmaceutical processing. Therefore, this study utilizes different machine learning scenarios to simulate the solubility of twelve non-steroidal anti-inflammatory drugs (NSAIDs) in the supercritical carbon dioxide (SCCO2). The considered NSAIDs are Fenoprofen, Flurbiprofen, Ibuprofen, Ketoprofen, Loxoprofen, Nabumetone, Naproxen, Nimesulide, Phenylbutazone, Piroxicam, Salicylamide, and Tolmetin. Physical characteristics of the drugs (molecular weight and melting temperature), operating conditions (pressure and temperature), and solvent property (SCCO2 density) are effectively used to estimate the drug solubility. Monitoring and comparing the prediction accuracy of twelve intelligent paradigms from three categories (artificial neural networks, support vector regression, and hybrid neuro-fuzzy) approves that adaptive neuro-fuzzy inference is the best tool for the considered task. The hybrid optimization strategy adjusts the cluster radius of the subtractive clustering membership function to 0.6111. This model estimates 254 laboratory-measured solubility data with the AAPRE = 3.13%, MSE = 2.58 × 10–9, and R2 = 0.99919. The leverage technique confirms that outliers may poison less than four percent of the experimental data. In addition, the proposed hybrid paradigm is more reliable than the equations of state and available correlations in the literature. Experimental measurements, model predictions, and relevancy analyses justified that the drug solubility in SCCO2 increases by increasing temperature and pressure. The results show that Ibuprofen and Naproxen are the most soluble and insoluble drugs in SCCO2, respectively. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to optimize the Flurbiprofen (FB) nanosuspension (NS) based gel and to investigate the in vitro release, ex vivo permeation, the plasma concentration-time profile and pharmacokinetic parameters. Methods: FB-NSs were developed using the wet milling process with the Design of Experiment (DoE) approach. The optimum FB-NS was characterized on the basis of SEM, DSC, XRPD, solubility and permeation studies. The dermal gel was prepared by incorporating FB-NS into HPMC gel. Then the in-vitro release, ex vivo permeation studies were performed, and pharmacokinetic studies were evaluated on rats. Results: The particle size, polydispersity index and zeta potential values of optimum NS were determined as 237.7 ± 6.8 nm, 0.133 ± 0.030 and − 30.4 ± 0.7 mV, respectively. By means of the surfactant content and nanosized particles of the nanosuspension, the solubility of FB was increased about 7-fold. The percentage permeated amount of FB from FB-NS gel (8.40%) was also found to be higher than the physical mixture (5.25%) and coarse suspension (reference) (2.08%) gels. The pharmacokinetic studies showed that the Cmax of FB-NS gel was 2.5 times higher than the reference gel, while AUC0–24 was 2.96 times higher. Conclusion: FB-NSs were successfully prepared with a wet milling method and optimized with the DoE approach. The optimized FB nanosuspension gel provided better permeation and pharmacokinetic performance compared to FB coarse suspension gel. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs and antibiotics are classes of active pharmaceutical ingredients (APIs), which are continuously contaminating the ecosystem through various anthropogenic activities. Because of their pseudo-persistence in the aquatic environment and their potentially chronic effects on aquatic life, it is important to closely monitor their concentrations in the aquatic environment using a sensitive analytical method. Sustainable aqueous biphasic systems (ABSs) composed of ionic liquids and biodegradable organic salt (sodium malate) were proposed. The phase diagrams of the systems were firstly determined, and [N4444]Cl-based ABS was selected for the simultaneous extraction and preconcentration of seven APIs. With the developed ABS, extraction efficiencies of APIs close to 100% were obtained. For the developed method, limits of detection (LODs) of 45, 65, 76, 14, 60, 48, and 51 ng L–1 were obtained for indomethacin, ibuprofen, diclofenac, naproxen, ketoprofen, flurbiprofen, and chloramphenicol, respectively, providing from 1216- to 1238-fold improvement as compared with the analysis without preconcentration. From an economic and environmental point of view, we can predict the prospects and competitive position of the method developed. [ABSTRACT FROM AUTHOR]

A crosslinked polymer hybrid film, ipn-poly(vinyl cinnamate-graft-2-hydroxy ethyl methacrylate)-v-poly(ethylene glycol dimethacrylate) was synthesized by UV initiation using poly(vinyl cinnamate) (polyVCi), 2-hydroxy ethyl methacrylate (HEMA) monomer and ethylene glycol dimethacrylate (EGDMA) crosslinker. Benzophenone (Ph2CO), was used as the photoinitiator. The synthesis was optimized by changing the concentration of HEMA, Ph2CO, EGDMA, and UV irradiation time. PolyVCi undergoes photocrosslinking by 2 + 2 photocylo addition while the monomer/crosslinker couple, HEMA/EGDMA, undergoes free radical polymerization and crosslinking to form EGDMA crosslinked polyHEMA. Hence, simultaneous interpenetrating polymer network (IPN) formation occurs. The IPN consists of dual network of photocrosslinked polyVCi and EGDMA crosslinked polyHEMA chains. Grafting of HEMA/EGDMA chains on the polyVCi backbone also occur during network formation. The chemical functionalities present in the polyVCi/polyHEMA/polyEGDMA IPN films obtained were characterized by FTIR and SEM analysis. The contact angle measurements show enhanced wettability of the IPN film compared to polyVCi surface. TGA analysis confirms thermal stability of the films. Swelling behavior of the films examined in water and in ethanol reveals the effects of the chemical natures of polyVCi and polyHEMA as well as that of crosslinking on the hydrophilicity of the film. The films were tested as drug release matrices using flurbiprofen. The drug was loaded into the film matrix during IPN formation under UV irradiation. PolyVCi/polyHEMA/polyEGDMA IPN proved to be a suitable release matrix for flurbiprofen demonstrating controlled release behavior and zero-order release kinetics. The release mechanism was confirmed by its Ritger-Peppas "n" value (1.00 to 1.42), which indicates super case II release. [ABSTRACT FROM AUTHOR]

Background: Postanesthetic shivering is an unpleasant adverse event in surgical patients. A nonsteroidal anti-inflammatory drug has been reported to be useful in preventing postanesthetic shivering in several previous studies. The aim of this study was to evaluate the efficacy of flurbiprofen axetil being a prodrug of a nonsteroidal anti-inflammatory drug for preventing postanesthetic shivering in patients undergoing gynecologic laparotomy surgeries. Method: This study is a retrospective observational study. I collected data from patients undergoing gynecologic laparotomy surgeries performed between October 1, 2019, and September 30, 2020, at Kumamoto City Hospital. All the patients were managed with general anesthesia with or without epidural analgesia. The administration of intravenous 50 mg flurbiprofen axetil for postoperative pain control at the end of the surgery was left to the individual anesthesiologist. The patients were divided into two groups: those who had received intravenous flurbiprofen axetil (flurbiprofen group) and those who had not received intravenous flurbiprofen axetil (non-flurbiprofen group), and I compared the frequency of postanesthetic shivering between the two groups. Additionally, the factors presumably associated with postanesthetic shivering were collected from the medical charts. Intergroup differences were assessed with the χ2 test with Yates' correlation for continuity category variables. The Student's t test was used to test for differences in continuous variables. Furthermore, a multivariate logistic regression analysis was performed to elucidate the relationship between the administration of flurbiprofen axetil and the incidence of PAS. Results: I retrospectively examined the cases of 141 patients aged 49 ± 13 (range 21-84) years old. The overall postanesthetic shivering rate was 21.3% (30 of the 141 patients). The frequency of postanesthetic shivering in the flurbiprofen group (n = 31) was 6.5%, which was significantly lower than that in the non-flurbiprofen group (n = 110), 25.5% (p value = 0.022). A multivariate logistic regression analysis showed that administration of flurbiprofen axetil was independently associated with a reduced incidence of postanesthetic shivering (odds ratio 0.12; 95% confidence interval, 0.02-0.66, p value = 0.015). Conclusions: My result suggests that intraoperative 50 mg flurbiprofen axetil administration for postoperative pain control is useful to prevent postanesthetic shivering in patients undergoing gynecologic laparotomy surgeries. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy and safety of flurbiprofen axetil in postoperative analgesia in upper abdominal surgery. Methods: This was a multicenter, randomized, positive drug parallel controlled double-blind clinical study. Patients undergoing upper abdominal surgery were randomly divided to receive flurbiprofen axetil or tramadol. The VAS pain scores at rest and on coughing (pulmonary function training) were assessed immediately before drug usage (T1) to evaluate the efficacy of postoperative analgesia. Repeat assessment of the VAS was performed after T1. The timing of the recovery of the gastrointestinal function and the preoperative and postoperative IL-6, cortisol, and blood glucose levels were recorded as secondary endpoints. Vital signs and the occurrence of adverse reactions were evaluated for the assessment of safety. Results: A total of 240 patients were enrolled in the current study; 119 used flurbiprofen axetil for postoperative analgesia. The VAS scores at rest and on coughing did not differ between the two groups to a statistically significant extent (P > 0.05). However, the reduction of the VAS score at rest in the flurbiprofen axetil group was greater than that in the tramadol group at 4–24 h after T1. The reduction of the VAS score on coughing at 8 h after T1 was greater in the flurbiprofen axetil group. The incidence of adverse reactions was significantly lower in the flurbiprofen axetil group, with only one adverse reaction recorded. In contrast, 18 adverse reactions were reported in the tramadol group. Conclusion: Flurbiprofen axetil showed superior efficacy to tramadol in early postoperative analgesia after upper abdominal surgery. Flurbiprofen axetil was associated with a significantly lower incidence of adverse reactions in comparison to tramadol. [ABSTRACT FROM AUTHOR]

Quite a high percentage of newly discovered drugs are discarded due to their low aqueous solubility and variable bioavailability. Therefore, it is necessary to explore new methodologies for increasing the aqueous solubility of such drugs. Several procedures have been proposed for this purpose, including salt formation, particle size reduction or using surfactants. In this report, we have improved the aqueous solubility of flurbiprofen by employing aqueous solution of anionic (SDS, SDBS), cationic (DTAB, CTAB, TTAB), non-ionic (Triton X-100 and Triton X-114 and DDAO) and zwitterionic DDAPS surfactants. It is concluded that all of the surfactants increased the solubility of flurbiprofen which increased with the increasing surfactant concentration. The reason behind such a trend was that the drug is partitioned between micelles and the aqueous phase. An increase in aqueous solubility of the drug was correlated with the (molar) solubilization ratio (χ), partition coefficient of drug (KM) between micelle and water, binding constant (K1) and standard state Gibbs energy of solubilization ( Δ G s o ) of the drug in the micelles. The order of drug solubilization in nonionic and zwitterionic surfactants was found as Triton X-114 > Triton X-100 > DDAO > DDAPS. In the case of anionic surfactants, it was noted as SDBS > SDS, whereas cationic surfactants solubilized the drug in the order of CTAB > TTAB > DTAB. The differences in χ and log10KM are attributed to the structural features of the surfactants. The aggregation number, HLB, core volume of micelles and electrostatic interaction between drug and micelles play important roles in solubilization of drugs in micellar solutions. The nonionic surfactants proved to be better, due to their low critical micelle concentrations higher solubilization capability and nontoxic nature; they were also found to have better drug release profiles. [ABSTRACT FROM AUTHOR]

Abstract: Flurbiprofen (FBP) is a strong nonsteroidal anti-inflammatory drug which has analgesic, antipyretic and anti-inflammatory effects. Chlorhexidine gluconate (CHG) is a potent antibacterial agent. Nowadays, FBP and CHG as a combination are used in some pharmaceutical products. In this study, an analysis method was developed for the simultaneous determination of FBP and CHG using high performance liquid chromatography (HPLC) technique. During analysis, Agilent Poroshell 120 EC-C18 column was used as stationary phase with a guard column having the same properties. Sodium phosphate buffer solution (100 mM, pH 2.5) and acetonitrile were used as mobile phase. The chromatography was performed by gradient elution at a flow rate of 0.5 mL min−1. Analytes were detected at 248 nm using a diode array detector (DAD). The developed method was validated according to United States Pharmacopoeia. It was found to be linear in the concentration range between 1 and 25 ppm. Determination coefficient was 0.9999 for FBP and CHG. The developed method was applied successfully for HPLC analysis of commercial pharmaceutical products including FBP and CHG.Graphical abstract: [ABSTRACT FROM AUTHOR]

Purpose: Intravitreal delivery of non-steroidal anti-inflammatory drugs could be an effective way to treat macular edema caused by posterior segment inflammation. In this study, we evaluated the intravitreal bioavailability and anti-inflammatory efficacy of flurbiprofen in rabbit eyes. Methods: For pharmacokinetics, 0.1 ml of 7.66 mg/ml flurbiprofen solution was injected intravitreally and vitreous drug levels were analyzed at specific time points using LC-MS technique. For efficacy, 100 ng lipopolysaccharide of E.coli was injected intravitreally in rabbits to induce inflammation. The animals were separated in three groups and received intraocular flurbiprofen, dexamethasone and PBS to serve as control. Complete ocular examination and total cell count in aqueous fluid were determined to evaluate the extent of inflammation. Eyes were then enucleated for histopathology analysis. The efficacy in the uveitis model was determined by clinical signs of inflammation, total leukocyte count and histology findings. Results: No adverse events were observed during pharmacokinetic assessment. No signs of inflammation, hemorrhage or retina detachment were detected. The recovery of flurbiprofen from vitreous samples was 92.6%. The half-life of flurbiprofen was estimated to be 1.92 h with an elimination constant rate (K) of 0.36. Treatment with intraocular injections of flurbiprofen and dexamethasone significantly reduced total leukocyte count in a manner comparable to dexamethasone [reduction of 96.84% ( p < 0.05) and 97.44% (p < 0.05), respectively]. Histologic studies demonstrated significantly less signs of ocular inflammation after flurbiprofen injection compared to control eyes. Conclusions: Flurbiprofen is effective in suppressing inflammation in this experimental uveitis model. In our experimental setting, intravitreal flurbiprofen seem to have a therapeutic result comparable to dexamethasone. However, the half-life of the drug remains short, necessitating further research to prolong its presence in the vitreous cavity. [ABSTRACT FROM AUTHOR]

Background: The number of kidney injury due to nonsteroidal anti-inflammatory drugs (NSAIDs) is the largest among drug-induced kidney diseases. Newly developed NSAID plaster containing S-flurbiprofen (SFP) shows innovative percutaneous absorption. However, systemic exposure to SFP following the repeated application of 80 mg/day was estimated as comparable to that of oral 120 mg/day flurbiprofen and prolonged use of topical NSAIDs is common in clinical practice. Thus, we report the safety focusing on the kidney function after long-term application of SFP plaster (SFPP). Methods: A total of 201 osteoarthritis patients (mean age; 66.3, 151 females, mean estimated glomerular filtration rate; 74.6 mL/min/1.73 mm) were applied 40 or 80 mg SFPP for 52 weeks, and kidney function was examined by blood urea nitrogen (BUN), serum creatinine (SCr), eGFR, and urinalysis. Results: 161 (80.1%) patients completed 52-week application. In both groups of 40 and 80 mg, small but statistically significant increases were observed in BUN (mean 1.91 and 1.89 mg/dL, p < 0.05) and SCr (mean 0.019 and 0.022 mg/dL, p < 0.05). Although abnormal changes in laboratory test for renal function were observed in seven patients, all the changes were small and subclinical. Acute kidney injury was observed in two patients. Meanwhile, the investigators denied the relevance of SFPP according to the clinical course. Conclusion: Toward the end of 52-week application, a statistically significant increase in SCr was observed in both 40 and 80 mg, but increment was small and subclinical. Attention should be paid to kidney function when applying SFPP to patients with multiple risk factors. [ABSTRACT FROM AUTHOR]

Objective: Non-steroidal anti-inflammatory drugs have been shown to effectively decrease postoperative pain and reduce opioid requirements. Flurbiprofen axetil is an injectable non-selective cyclooxygenase inhibitor that has a high affinity for inflammatory tissues to achieve targeted drug therapy and prolonged duration of action. This meta-analysis examined the use of preoperative flurbiprofen axetil and its impact on postoperative analgesia. Methods: An electronic literature search of the Library of PubMed, Cochrane CENTRAL, and EMBASE databases was conducted in Feb 2016. Searches were limited to randomized controlled trials. The primary outcome was pain scores. The secondary outcomes included cumulative postoperative opioid consumption and opioid-related adverse effects. Results: A total of nine RCT studies involving 457 patients were included in this study. Compared to patients without perioperative flurbiprofen axetil, patients treated with preoperative flurbiprofen axetil had lower pain scores at 2 h (SMD −1.00; 95% CI −1.57 to −0.43, P = 0.0006), 6 h (SMD −1.22; 95% CI −2.01 to −0.43; P = 0.002), 12 h (SMD −1.19; 95% CI −2.10 to −0.28; P = 0.01), and 24 h (SMD −0.79; 95% CI −1.31 to −0.27; P = 0.003) following surgery. Preoperative flurbiprofen axetil had no significant effect on postoperative opioid consumption (SMD −13.11; 95% CI −34.56 to 8.33; P = 0.23). There was no significant difference between the groups with regard to adverse effects. Compared to patients with postoperative flurbiprofen axetil, however, preoperative flurbiprofen axetil resulted in decreased pain score only at 2 h after operation. Conclusions: Preoperative use of flurbiprofen axetil will result in significantly lower postoperative pain scores, but no difference in nausea, vomiting, and opioid consumption compared to those who did not receive flurbiprofen axetil. However, more homogeneous and well-designed clinical studies are necessary to determine whether preoperative flurbiprofen axetil administration has more efficacy than that given at the end of surgery. [ABSTRACT FROM AUTHOR]

A novel Ni complexed aminoclay (AC) catalyst was prepared by complexation method followed by reduction reaction. Various analytical techniques such as FTIR spectroscopy, UV-visible spectroscopy, DSC, TGA, SEM, HRTEM, EDX, XPS and WCA measurement are used to characterize the synthesized material. The AC-Ni catalyst system exhibited improved thermal stability and fiber-like morphology. The XPS results declared the formation of Ni nanoparticles. Thus, synthesized catalyst was tested towards the Schiff base formation reaction between various bio-medical polymers and aniline under air atmosphere at 85 °C for 24 h. The catalytic activity of the catalyst was studied by varying the % weight loading of the AC-Ni system towards the Schiff base formation. The Schiff base formation was quantitatively calculated by the H-NMR spectroscopy. While increasing the % weight loading of the AC-Ni catalyst, the % yield of Schiff base was also increased. The k and Ti values were determined for the reduction of indole and α-terpineol in the presence of AC-Ni catalyst system. The experimental results were compared with the literature report. [ABSTRACT FROM AUTHOR]

The present study aimed to improve solubility and prolong the release duration of a poorly soluble drug using a combination of two different types of formulations (solid dispersion and microspheres). The solid dispersions were prepared by fusion method using urea and mannitol as hydrophilic carriers. Microspheres were prepared by solvent evaporation method using Eudragit L-100 (EL100) and Eudragit RS PO (ERS) as rate-controlling polymers. Flurbiprofen (FBP)-urea (1:2) solid dispersion and microspheres of FBP-EL-100-ERS (1:0.25:0.75) were used for the development of controlled release formulation by mixing them in different proportions. The FBP-containing formulations were evaluated for percentage yield, drug content, morphology, in vitro release, and in vivo anti-inflammatory activity. The best selected formulation was further evaluated for the controlled and improved effects. SEM photomicrograph confirmed the spherical shape of microspheres and with particle size in the range of 73.5-85.4 μm. In vitro release of FBP from controlled release formulations indicated that the formulation containing solid dispersion:microspheres (1:0.5) yielded prolonged effect up to 10 h. The release kinetics followed zero-order, and the mechanism of drug release was found to be diffusion rate controlled. This formulation had shown better inhibition of edema of rat paw up to 16 h and identified as a suitable product for controlled delivery of FBP. In conclusion, the concept of using a binary mixture of solid dispersion and microspheres can be used for other drugs that exhibit a poor solubility in stomach pH and a faster release in intestinal pH. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to enhance the dissolution and oral absorption of poorly water-soluble active pharmaceutical ingredients (APIs) using nanoparticle suspensions prepared with a PureNano™ continuous crystallizer (PCC). Method: Nanoparticle suspensions were prepared with a PCC, which is based on microfluidics reaction technology and solvent-antisolvent crystallization. Phenytoin, bezafibrate, flurbiprofen, and miconazole were used as model APIs. These APIs were dissolved in ethanol and precipitated by the addition of water and polyvinyl alcohol. Batch crystallization (BC) using a beaker was also performed to prepare the suspensions. Both PCC and BC formulations were freeze-dried before being characterized in vitro and in vivo. Results: The particle sizes of the nanoparticle suspensions prepared with the PCC were smaller than those prepared by BC. The dissolution rate of each API in vitro significantly increased after crystallization. Reducing the particle size of either the BC or PCC formulation led to increased API flux across Caco-2 cell monolayers. PCC preparations showed higher plasma concentrations after oral administration, demonstrating the advantages of a fast dissolution rate and increased interaction with the gastrointestinal tract owing to the smaller particle size. Conclusions: PCC can continuously produce nanoparticle APIs and is an efficient approach for improving their oral bioavailability. [ABSTRACT FROM AUTHOR]

Background and objectives: The newly developed S-flurbiprofen plaster (SFPP) is a tape-type patch that shows innovative percutaneous absorption. This study was designed to evaluate the safety of a long-term 52-week SFPP application to osteoarthritis (OA) patients. Methods: This was a multi-center, open-label, uncontrolled prospective study that included 201 OA patients. SFPP at 40 mg/day was applied to the site of pain in 101 patients and at 80 mg/day (2 patches) in 100 patients at a total of 301 sites for 52 weeks. The affected sites assessed included the knee (192), lumbar spine (66), cervical spine (26), and others (17). Drug safety was evaluated by medical examination, laboratory tests, and examination of vital signs. Efficacy was evaluated by the patient's and clinician's global assessments and clinical symptoms. Results: Most patients (80.1 %) completed the 52-week SFPP application. The majority of drug-related adverse events (AEs) included mild dermatitis at the application sites and occurred in 46.8 % of the sites. No photosensitive dermatitis was observed. Systemic AEs occurred in 9.0 % of the patients; a serious AE (gastric ulcer hemorrhage) occurred in one patient. No clinically significant changes in the laboratory tests and vital signs were observed. The efficacy evaluation showed an improvement from 2 weeks after the SFPP application, which continued during the 52 weeks' treatment. Conclusions: No apparent safety concerns were observed, even during the long-term SFPP application. Therefore, SFPP could be an additional pharmacotherapy in OA treatment. [ABSTRACT FROM AUTHOR]

Objective: Acetaminophen is known to be a relatively weak analgesic with fewer side effects than nonsteroidal anti-inflammatory drugs (NSAIDs). This study aimed to determine whether intravenous (iv) acetaminophen produces comparable analgesic effects to those of flurbiprofen (positive control drug), an intravenously injectable NSAID, after partial mastectomies. The primary outcome assessed was pain intensity during the first 24 h after the operation, and the secondary outcome was the satisfaction rating at discharge. Methods: After obtaining Institutional Ethics Committee approval, a series of 40 consecutive female patients who were scheduled for partial mastectomies were enrolled. Participants were randomly divided into two groups: an acetaminophen (1000 mg × 3) group (group A) and a flurbiprofen (50 mg × 3) group (group F). Each drug was administered 15 min before the end of surgery, and at 6 and 12 h after the operation. Postoperative pain was evaluated using a 100-mm visual analog scale (VAS) at 3, 6, and 24 h postoperatively. Satisfaction rating was evaluated on a 5-point scale (very good, good, well, bad, and very bad). Results: VAS scores (mm) with movement in groups A and F at 3, 6, and 24 h after the surgery were 22 vs. 28, 14 vs. 24, and 12 vs. 20.5 (median), respectively, with no significant differences between the two groups. Eighteen of 20 patients in group A and 20 of 20 patients in group F expressed a satisfaction rating of greater than good. Conclusions: Acetaminophen produces an equivalent analgesic effect to flurbiprofen in post-partial mastectomy patients. [ABSTRACT FROM AUTHOR]

Flurbiprofen axetil (FPA) is an injection product and a prodrug of a non-steroidal anti-inflammatory drug (NSAID). After injection, it is rapidly hydrolyzed to the active form, flurbiprofen (FP). Since frequent injections of FPA can lead to abnormal physiology, an administration strategy is necessary to ensure there is enhancement of the analgesic efficiency of FP after a single dose and to reduce the total number of doses. FP strongly binds to site II of albumin, and thus the free (unbound) FP concentration is low. This study focused on 6-methoxy-2-naphthylacetic acid (6-MNA), the active metabolite of nabumetone (a prodrug of NSAID). We performed ultrafiltration experiments and pharmacokinetics analysis in rats to investigate whether the inhibitory effect of 6-MNA on FP binding to albumin increased the free FP concentration in vitro and in vivo. Results indicated that 6-MNA inhibited the binding of FP to albumin competitively. When 6-MNA was injected in rats, there was a significant increase in the free FP concentration and the area under concentration-time curve (AUC) calculated from the free FP concentration, while there was a significant decrease in the total (bound + free) FP concentration and the AUC calculated from the total FP concentration. These findings indicate that 6-MNA inhibits the protein binding of FP in vivo. This suggests that the frequency of FPA injections can be reduced when administered with nabumetone, as there is increase in the free FP concentration associated with pharmacological effect. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to investigate the pharmacokinetics and deep tissue penetration capability of the newly developed S-flurbiprofen plaster (SFPP) in humans. Methods: Study 1: SFPP tape-type patch (2-60 mg) was applied to the lower back for 24 h in healthy adult volunteers. S-flurbiprofen (SFP) plasma concentration was measured over time to examine SFP pharmacokinetics. Study 2: SFPP (20 mg) was applied for 12 h to the affected knee of osteoarthritis (OA) patients who were scheduled for total knee arthroplasty. Deep tissues (synovial tissue and synovial fluid) were collected during surgery to compare SFP concentrations after application of SFPP or a commercially available flurbiprofen (FP) gel-type patch. Results: Study 1: The plasma concentration of SFP was sustained during 24-h topical application of the SFPP, showing a high percutaneous absorption ratio of 51.4-72.2 %. C and AUC were dose-proportional. Study 2: After application of the SFPP for 12 h, SFP concentrations in the synovial tissue and synovial fluid were 14.8-fold ( p = 0.002) and 32.7-fold ( p < 0.001) higher, respectively, than those achieved by the FP patch. Conclusions: Sustained plasma concentration of SFP and high percutaneous absorption ratio was observed after 24-h topical application of the SFPP. Compared to the FP patch, the SFPP showed superior percutaneous absorption and greater tissue penetration of SFP into the synovial tissue. Greater tissue penetration of the SFPP seemed to be primarily due to its formulation. Thus, SFPP is expected to show higher efficacy for the treatment of knee OA. [ABSTRACT FROM AUTHOR]

Purposes: In the present study, we investigated whether flurbiprofen axetil (FA) alleviates hypoxemia during one-lung ventilation (OLV) by reducing the pulmonary shunt/total perfusion ( Q/ Q) ratio, and examined the relationship between the Q/ Q ratio and the thromboxane B (TXB)/6-keto-prostaglandin F1α (6-K-PGF1α) ratio. Methods: Sixty patients undergoing esophageal resection for carcinoma were randomly assigned to groups F and C ( n = 30 for each group). FA and placebo were administered i.v. 15 min before skin incision in groups F and C, respectively. The partial pressure of arterial oxygen (PaO) was measured and the Q/ Q ratio was calculated. Serum TXB, 6-K-PGF1α, and endothelin (ET) were measured by radioimmunoassay. The relationship between TXB/6-K-PGF1α and Q/ Q was investigated. Results: Compared with group C, PaO was higher and the Q/ Q ratio was lower during OLV in group F ( P < 0.05). After treatment with FA, both serum TXB and 6-K-PGF1α decreased significantly ( P < 0.05) but the TXB/6-K-PGF1α ratio increased significantly ( P < 0.01). Increases in the TXB/6-K-PGF1α ratio were correlated with reductions in the Q/ Q ratio during OLV in group F ( r = −0.766, P < 0.01). There was no significant difference in serum ET between groups F and C. Conclusions: Treatment with FA reduced the Q/ Q ratio and further increased the PaO level during OLV, possibly due to upregulation of the vasoactive agent TXB/6-K-PGF1α ratio. [ABSTRACT FROM AUTHOR]

The present work explores inner structuration of in situ gelling system consisting of glyceryl monooleate (GMO) and oleic acid (OA). The system under study involves investigation of microstructural changes which are believed to govern the pharmaceutical performance of final formulation. The changes which are often termed mesophasic transformation were analysed by small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), rheology and plane polarised light (PPL) microscopy. The current work revealed transformation of blank system from W/O emulsion to reverse hexagonal structure upon addition of structural analogues of ibuprofen. Such transformations are believed to occur due to increased hydrophobic volume within system as probed by SAXS analysis. The findings of SAXS studies were well supported by DSC, rheology and PPL microscopy. The study established inverse relationship between log P value of structural analogues of ibuprofen and the degree of binding of water molecules to surfactant chains. Such relationship had pronounced effect on sol-gel transformation process. The prepared in situ gelling system showed sustained drug release which followed Higuchi model. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the impact of CYP2C9*1/*3 genotype on the pharmacokinetics of flurbiprofen and its metabolite. The CYP2C9 genotypes were determined with the use of polymerase chain reaction and restriction fragment and DNA sequencing analysis in 358 healthy Koreans. Among them, twenty individuals with CYP2C9*1/*1 (n = 12) or CYP2C9*1/*3 (n = 8) genotypes received a single 40 mg oral dose of flurbiprofen. The plasma concentrations of flurbiprofen and its metabolite, 4′-hydroxyflurbiprofen were measured by HPLC. AUC of flurbiprofen was significantly higher and its clearance was significantly lower in the CYP2C9*1/*3 individuals than in those with CYP2C9*1/*1. The AUC ratio of 4'-hydroxyflurbiprofen to flurbiprofen was significantly lower in the CYP2C9*1/*3 individuals than in those with CYP2C9*1/*1. These results indicate that the individuals carrying of CYP2C9*3 have significant reduction in flurbiprofen metabolism. The clinical use of this information may allow for more efficient personalized pharmacotherapy. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to investigate the effects of anti-inflammatory drugs (ADs) on intravenous immunoglobulin (IVIG) therapy in the acute phase of Kawasaki disease. In total, 182 pediatric patients who received IVIG therapy for Kawasaki disease between 1999 and 2013 at the Department of Pediatrics, Aomori Prefectural Central Hospital were enrolled. Patients were divided into 2 groups: an S group, including 111 patients who received single IVIG therapy with delayed administration of ADs, and a T group, including 71 patients who received concomitant AIDs with IVIG. During the study, the only ADs administered were aspirin (A: 30 mg/kg/day) or flurbiprofen (F: 3-5 mg/kg/day). Steroids were not administered to any patient. The regimen of the S group was partially used after 2004 and was used to all patients after 2009. The following clinical findings were significantly different between the S and T groups: disease onset before 2003 (0 vs. 59 %, P < 0.001) and after 2009 (70 vs. 0 %, P < 0.001), use of 2-g/kg/day IVIG therapy (100 vs. 93 %, P = 0.034), ADs type (A/F: 62/49 vs. 17/54, P < 0.001), and the prevalence of coronary artery lesions (CAL) up to (1/111 vs. 11/71, P < 0.001) and after 30 days of illness (0/111 vs. 4/71, P = 0.022). Logistic regression analysis revealed that IVIG therapy only (S group; P = 0.009) and 2-g/kg/day IVIG therapy ( P = 0.015) were significant factors for CAL suppression. The findings revealed a possible negative impact of ADs on initial IVIG therapy in the acute phase of Kawasaki disease. Initial single IVIG therapy with delayed administration of ADs may be useful to suppress CAL caused by Kawasaki disease. [ABSTRACT FROM AUTHOR]

The complexation process between racemic flurbiprofen and β-cyclodextrin in solution was investigated by 1D and 2D proton NMR spectroscopy. In the presence of β-cyclodextrin, the aromatic protons of flurbiprofen were the most affected, suggesting a strong involvement of the phenyl groups in the inclusion mechanism. The stoichiometry of the complex was determined by the method of continuous variation, using the chemical induced shifts of both host and guest protons. The association constant, K of the obtained complex was calculated and found to be 2483.8 M. On the other hand, signals belonging to the protons associated with the carboxyl group are split in the presence of β-cyclodextrin indicating enantiomeric differentiation. Rotating frame NOE spectroscopy, (ROESY), was used to ascertain the solution geometry of the host-guest complex. The result suggested that the flurbiprofen molecule fully penetrates the β-cyclodextrin cavity with the carboxyl group protruding from the primary hydroxyl side and the phenyl group close to the secondary rim. [ABSTRACT FROM AUTHOR]

A simple, sensitive, precise, rapid, and reliable high-performance thin-layer chromatographic (HPTLC) method for the simultaneous estimation of sparfloxacin (SPF) and flurbiprofen (FLB) in bulk drug as well as in dual drug loaded poly-(lactic-co-glycolic acid) (PLGA) nanoparticles was developed. In this method, aluminumbacked silica gel 60 F254 plates (20 × 10 cm: 200 μm thickness) were used as stationary phase and chloroform-methanol-formic acid (7.5:1:1, v/v) as an optimized mobile phase. Developed chromatogram was scanned at 258 nm, the wavelength of maximum absorption SPF and FLB. Regression analysis of the calibration data showed an excellent linear relationship between peak area versus drug concentration. Linearity was found to be in the range of 100-600 ng spot-1 and 40-800 ng spot-1 for SPF and FLB, respectively. The suitability of the developed HPTLC method for simultaneous estimation of SPF and FLB was established by validating it as per the ICH guidelines. The limits of detection (LOD) and quantification (LOQ) for SPF were found to be ≈13 and ≈40 ng spot-1, respectively, and those for FLB ≈27 ng spot-1 and ≈82 ng spot-1, respectively. The developed method was found to be linear (r² = 0.999), precise (% RSD < 1.5% repeatability and <2.55% for intermediate precision), accurate (mean recovery of within the range of 98-102%), specific, and robust. Stress-induced degradation studies revealed the suitability of method for the quantitative determination of drugs in the presence of degradants. The developed method has been successfully applied for the determination of entrapment efficiency, drug loading, in vitro drug release profile and stability assessment of dual drug loaded PLGA nanoparticles (NPs). [ABSTRACT FROM AUTHOR]

Flurbiprofen was formulated into nanoparticle suspension to improve its oral bioavailability. Hydroxypropyl-β-cyclodextrin inclusion-flurbiprofen complex (HP-β-CD-FP) was prepared, then incorporating this complex into poly(alkyl-cyanoacrylate) (PACA) nanoparticles. HP-β-CD-FP-PACA nanoparticle was prepared by the emulsion solvent polymerization method. The zeta potential was −26.8 mV, the mean volume particle diameter was 134 nm, drug encapsulation efficiency was 53.3 ± 3.6 % and concentration was 1.5 mg/mL. The bioavailability of flurbiprofen from optimized nanoparticles was assessed in male Wistar rats at a dose of 15 mg/kg. As compared to the flurbiprofen suspension, 211.6 % relative bioavailability was observed for flurbiprofen nanoparticles. The reduced particle size and increased surface area may contribute to improve oral bioavailability of flurbiprofen. [ABSTRACT FROM AUTHOR]

A novel series of new flurbiprofen hydrazide derivatives 2-(2-fluorobiphenyl-4-yl)- N′-[(substituted phenyl/5-nitro-2-furyl)methylene]propanehydrazide ( 3a- k), 2-(2-fluorobiphenyl-4-yl)- N-(2-substituted-4-oxo-1,3-thiazolidine-3-yl)propanamide ( 4a- b, 4d- k), 2-[2-(2-fluorobiphenyl-4-yl) propanoyl]- N-substituted hydrazinecarbothioamide ( 5a- h) and 2-(2-fluorobiphenyl-4-yl)- N′-[(3-methyl-4-oxo-1,3-thiazolidin-2-ylidene]propanehydrazide ( 6a- b, 6e and 6g) has been synthesized in this study. All synthesized compounds were screened for antimicrobial activity against various bacterial and fungal strains. Additionally, compounds were evaluated for the ability to inhibit Hepatitis C virus NS5B polymerase. The most active 4-thiazolidinone compound was 4k (SGK119) with 67.0 % and thiosemicarbazide compound was 5d (SGK123) with 69.50 % inhibition at 200 μM against hepatitis C virus NS5B RNA polymerase. Anticancer activity of the selected compounds ( 3i, 3j, 3h, 4d, 4i and 6b) was determined at a single dose towards the full panel of 60 human cancer cell lines by the National Cancer Institute (NCI). 2-(2-Fluoro-4-biphenylyl)- N-[2-[4-(trifluoromethyl)phenyl]-4-oxo-1,3-thiazolidine-3-yl]propanamide 4d, containing thiazolidinone ring, demonstrated the most marked effect with 20.80 % growth percent on leukaemia cancer cell line SR at 10 M. The results demonstrated that none of the compounds tested have anticandidal and antifungal activities, but two of them ( 4a and 4i) showed antibacterial inhibition against Micrococcus luteus, and Staphylococcus cohnii and Staphylococcus aureus, respectively. [ABSTRACT FROM AUTHOR]