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The design of this study is to compare the effectiveness of two analgesic drugs in the intervention of pain events for patients on mechanical ventilation. 414 patients from three hospitals with respiratory failure requiring mechanical ventilation were randomly assigned to oxycodone hydrochloride or flurbiprofen axetil. The primary endpoints is the difference in the proportion of patients with a Behavioral Pain Scale (BPS) score > 5 within 48 h. The secondary endpoints is to compare the dosage of sedative drugs (midazolam, propofol, dexmedetomidine) and to assess the clinical outcomes such as duration of mechanical ventilation. There was no significant difference in BPS scores between the two groups at enrollment, and BPS scores in oxycodone group were significantly lower than those in flurbiprofen axetil group at 24 and 48 h of enrollment. The proportion of patients with BPS less than 5 points in the Oxycodone hydrochloride group was also significantly lower than that in the flurbiprofen axetil group. For patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 10, subgroup analysis showed that the mechanical ventilation time of oxycodone hydrochloride group was significantly lower than that of flurbiprofen axetil group with statistical significance, and the dosage of midazolam was significantly lower than that of flurbiprofen axetil group. The length of ICU stay was significantly lower than that of flurbiprofen axetil group. Oxycodone hydrochloride was more potent than flurbiprofen axetil for analgesia for patients with respiratory failure requiring mechanical ventilation. [ABSTRACT FROM AUTHOR]

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain disorders and exert pharmacological effects by inhibiting cyclooxygenase (COX). Although previous studies have evaluated the COX inhibitory activity and selectivity of NSAIDs, none has compared COX inhibitory concentrations with the plasma concentrations of clinical doses or investigated the efficacy and adverse effects of different dosage forms. Therefore, in this study we evaluated the COX inhibitory activities and inhibition rates of clinical doses of the various NSAID formulations, especially diclofenac sodium. Methods: Human blood and the drug (diclofenac sodium, celecoxib, ibuprofen, flurbiprofen, or etodolac) were mixed and incubated, and the supernatant was collected and quantified the COX inhibitory activity of each drug by ELISA. Logistic regression analyses were used to calculate the inhibition rates at maximum plasma drug concentration (Cmax) of clinical doses of marketed formulations. For diclofenac sodium, we also calculated the concentrations at which COX inhibition rates were 50% and 80% (IC50 and IC80). Results: COX-2 inhibition rate at Cmax of clinical doses exceeded 50% except celecoxib 100 mg. For diclofenac sodium, the Cmax at the clinical doses of the oral and suppository formulations showed almost complete inhibition of COX-2 and an inhibition rate exceeding IC80 for COX-1. The Cmax at repeated doses of the transdermal formulation showed an inhibition rate above IC80 for COX-2 but below IC80 for COX-1. Discussion: This result explains why gastrointestinal disorders frequently occur with oral and suppository formulations of diclofenac sodium despite its relatively high COX-2 selectivity. Although the plasma drug concentration of the transdermal formulation is lower than oral and suppository formulations, it has an inhibition rate above IC50 for COX-2, which is required for analgesic efficacy, and has a lower COX-1 inhibition rate than these formulations. Conclusion: The findings explain why the transdermal formulation exerts an analgesic effect despite having a lower Cmax than other diclofenac sodium formulations. [ABSTRACT FROM AUTHOR]

Flurbiprofen (FBP) is poorly water-soluble BCS class II drug with anti-inflammatory and analgesic effects, used to treat arthritis and degenerative joint diseases. This study was aimed to develop SNEDDS loaded with FBP. Six SNEDDS using two oils olive oil (F1OLV, F2OLV, F3OLV) and castor oil (F4CAS, F5CAS, F6CAS) with three different Smix ratios consisting of Tween 20 and PEG 400 (1:1, 1:2, 2:1) were prepared and characterized. Compatibility between FBP and polymers was investigated using FTIR. SNEDDS were characterized for physicochemical attributes. Two optimized formulations were investigated at 10 mg/kg dose given orally in Wistar rats for analgesic activity by hot plate and tail flick methods, and anti-inflammatory activity by carrageenan induced paw edema method. Anti-inflammatory activity was further explored by motor coordination and motility by Rota rod and cage activity tests. Following anesthesia blood samples were collected before dissection to measure inflammatory mediators and oxidative stress markers. Sciatica nerves and hind paws of rats were also removed for histopathological evaluation. FTIR studies revealed compatibility of FBP with other components. Droplet size of F1OLV, F2OLV, F3OLV was 128.5 ± 0.7 nm, 202.5 ± 1.3 nm, and 541.5 ± 1.7 nm, whereas it was 142.5 ± 1.1 nm, 215.4 ± 1.2 nm and 349.9 ± 1.8 nm for F4CAS, F5CAS, F6CAS. %EE of F1OLV, F2OLV, F3OLV was found 85 ± 4.89%–91 ± 4.67%, whereas the %EE F4CAS, F5CAS, F6CAS was 84 ± 4.15%–90 ± 4.21%. DSC curves of F1OLV and F4CAS revealed amorphous nature of the FBP. SEM showed spherical shape of globules. % of drug released in the pH medium 1.2 for plain FBP, F1OLV and F4CAS was 25%, 59% and 57%. % drug released in the pH 6.8 for plain FBP, F1OLV and F4CAS was 59%, 85% and 83%. Oral administration of FBP-loaded SNEDDS (F1OLV and F4CAS) significantly decreased paw diameter and enhanced motor coordination in rats when compared to the disease control group. This was linked to the ability of FBP to reduce inflammation and oxidative stress, with histological studies indicating decreased tissue damage in SNEDDS treated groups, implying the possibility of tissue recovery. Administration of both formulations started to demonstrate analgesic and anti-inflammatory effects after one hour of administration. In addition to anti-inflammatory effect, both formulations improved motor coordination, motility, and reduced infiltration of inflammatory cells in the inflamed paws. The anti-inflammatory and analgesic activities were attributed to decreased serum levels of IL-6 and TNF-α, increased activity of SOD and reduced nitrite content in sciatic nerves. Histopathological evaluation revealed reduced vascularity, inflammation and synovial hyperplasia. The overall findings suggest that the FBP loaded SNEDDS can be used as carriers for improved delivery of FBP which can effectively be used to cure pain and inflammation. [ABSTRACT FROM AUTHOR]

Juice and decoction of leaves of Suaeda fruticosa, a halophytic medicinal plant of Cholistan desert, is traditionally used to treat rheumatism. The current study was carried out to probe into in vivo anti-nociceptive, anti-inflammatory, and anti-arthritic potential of ethanolic extract of the whole plant of S. fruticosa (Et-SF) and its bioactive molecules. GC–MS screening of Et-SF revealed presence of various bioactive compounds including phytol, thymol, n-hexadecanoic acid, farnesol, and 1-heptacosanol. DPPH in vitro radical scavenging assay demonstrated moderate antioxidant potential of Et-SF. Safety evaluation of Et-SF confirmed no lethal effects in female albino rats up to the single oral dose of 5000 mg/kg. In all in vivo models, Et-SF was administered in three doses (125, 250, and 500 mg/kg) and a single dose of flurbiprofen (FP) (10 mg/kg). Et-SF significantly (p < 0.05) attenuated acute inflammation in carrageenan, histamine, and serotonin-induced rat paw oedema models in a time-dependent manner. Et-SF alleviated oedema, restored haematological parameters, and reduced severe pannus formation, inflammatory cell infiltration, and fibrous tissue proliferation in the paws of CFA-induced arthritic rats. Moreover, treatment with thymol, farnesol and n-hexadecanoic acid alone and in combination also attenuated the arthritic progression in the arthritic rats indicating involvement of these compounds towards anti-arthritic potential of Et-SF. Et-SF and FP significantly (p < 0.05) down-regulated IL-1β, TNF-α, IL-6, NF-κB, and COX-2 mRNA expression, and up-regulated IL-4 and IL-10 mRNA expression in arthritic rats. Hot plate and acetic acid-induced writhing models results indicated the analgesic attributes of Et-SF in mice models. This study suggests that S. fruticosa ethanol extract may regulate the expression of inflammatory markers involved in nociceptive, inflammatory, and arthritic disorders. Its phytochemicals could target multiple phases of these conditions at cellular and subcellular levels. Further research is needed to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

This study aims to develop and evaluate flurbiprofen-loaded polymeric nanoparticles to achieve sustained drug release, enhancing therapeutic efficacy and minimising dosing frequency for improved patient outcomes. Flurbiprofen-loaded polymeric nanoparticles were prepared using a tubular microreactor and spray drying, optimised via Box-Behnken Design. Characterisation included particle size, encapsulation efficiency, in vitro and in vivo drug release, and techniques like FTIR, DSC, XRD, and SEM. Statistical analysis ensured robust formulation optimisation and evaluation of performance. The optimised batch of flurbiprofen-loaded polymeric nanoparticles was characterised for mean diameter, PDI, zeta potential, drug release, and EE% were found to be 306.1 ± 6.00 nm, 0.184 ± 0.02 Mw, −23.6 ± 1.51 mV, 85.46 ± 0.53% and 92.31 ± 0.84 (% w/w) respectively. Pharmacokinetic analysis further confirmed the sustained release, extending up to 12 hours and enhancing permeation compared to the pure flurbiprofen. Sustained release of flurbiprofen-loaded polymeric nanoparticles significantly enhances therapeutic effectiveness for inflammatory conditions. [ABSTRACT FROM AUTHOR]

Purpose: Nonsteroidal anti-inflammatory drugs (NSAID) are associated with increased stress fracture risk, potentially due to inhibiting the adaptive bone formation responses to exercise. This study investigated if a single, maximal dose of three different NSAID alters bone formation biomarker response to strenuous exercise. Methods: In a randomized, counterbalanced order, 12 participants (10 male, 2 female), performed four bouts of plyometric jumps, each separated by at least 1 wk. Two hours before exercise, participants consumed either placebo or NSAID: ibuprofen (800 mg), celecoxib (200 mg), flurbiprofen (100 mg). Blood was collected before (PRE), and at 0, 15, 60, 120, and 240 min postexercise. Parathyroid hormone, ionized calcium, procollagen type 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin, C-terminal telopeptide of type 1 collagen, tartrate-resistant acid phosphatase, and sclerostin were measured. Prostaglandin E2 metabolite and creatinine were measured in urine. Data were analyzed using repeated-measures ANOVA and area under the curve analysis. Data are mean ± SD. Results: There was an exercise effect for procollagen type 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin, C-terminal telopeptide of type 1 collagen, tartrate-resistant acid phosphatase, sclerostin, osteoprotegerin, parathyroid hormone, and ionized calcium (all P < 0.05), but no NSAID treatment effect for any biomarker (all P > 0.05). Area under the curve analyses were not different for any biomarker (P > 0.05). Prostaglandin E2 metabolite was higher during the placebo trial (322 ± 153 pg·mg−1 creatinine, P < 0.05) compared with ibuprofen (135 ± 83 pg·mg−1), celecoxib (202 ± 107 pg·mg−1), and flurbiprofen (159 ± 74 pg·mg−1). Conclusions: Plyometric exercise induced changes in bone metabolism, but the responses were unaltered by consuming NSAID 2 h before exercise. [ABSTRACT FROM AUTHOR]

PURPOSE: Oxycodone is a potent μ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia on postoperative pain following major laparoscopic gastrointestinal surgery. METHODS: In this randomised double-blind controlled trial, 40 adult patients were randomised (1:1, stratified by type of surgery) to receive oxycodone- or sufentanil-based multimodal analgesia, comprising bilateral transverse abdominis plane blocks, intraoperative dexmedetomidine infusion, flurbiprofen axetil, and oxycodone- or sufentanil-based patient-controlled analgesia. The co-primary outcomes were time-weighted average (TWA) of visceral pain (defined as intra-abdominal deep and dull pain) at rest and on coughing during 0-24 h postoperatively, assessed using the numerical rating scale (0-10) with a minimal clinically important difference of 1. RESULTS: All patients completed the study (median age, 64 years; 65% male) and had adequate postoperative pain control. The mean (SD) 24-h TWA of visceral pain at rest was 1.40 (0.77) in the oxycodone group vs 2.00 (0.98) in the sufentanil group (mean difference=-0.60, 95% CI, -1.16 to -0.03; P=0.039). Patients in the oxycodone group had a significantly lower 24-h TWA of visceral pain on coughing (2.00 [0.83] vs 2.98 [1.26]; mean difference=-0.98, 95% CI, -1.66 to -0.30; P=0.006). In the subgroup analyses, the treatment effect of oxycodone vs sufentanil on the co-primary outcomes did not differ in terms of age (18-65 years or >65 years), sex (female or male), or type of surgery (colorectal or gastric). Secondary outcomes (24-h TWA of incisional and shoulder pain, postoperative analgesic usage, rescue analgesia, adverse events, and patient satisfaction) were comparable between groups. CONCLUSION: For patients undergoing major laparoscopic gastrointestinal surgery, oxycodone-based multimodal analgesia reduced postoperative visceral pain in a statistically significant but not clinically important manner. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100052085).

In this study, SeDeM–ODT parametric tests were performed to determine the use of ludipress as a directly compressible tableting excipient for the development of a flurbiprofen orally disintegrating tablet. The preformulation features of different formulations (F1 –F9) were analyzed by the SeDeM–ODT tool which showed that all the powder blends were appropriate for direct compression since all the blends had index of good compressibility and bucodispersibility (IGCB) values above 5, signifying direct compression is the most appropriate method. The powder blend of the optimized formulation was assessed by the DSC–TGA technique. The optimization of nine different formulations blends of orally disintegrating tablets (ODTs) was prepared in various ratios by the implementation of design of experiments (DoE), using the central composite design by selecting ludipress (X1) (49–55%) and croscarmellose sodium (X2) (1–5%) while hardness, friability, and disintegration tests were selected as responses. The optimized formulations were evaluated by various tests and the results indicated that all the formulations were found to be in adequate range. Formulations were subjected to stability studies at accelerated states following ICH guidelines. Shelf life was found to be 51.144–56.186 months. Results of multiple-point dissolution studies revealed that formulations followed the Higuchi kinetic model. This study revealed that the SeDeM—ODT tool has been successfully used to determine the compression behavior of active compounds and their powder blends for the direct compression (DC) method in formulating flurbiprofen–ODT tablets. [ABSTRACT FROM AUTHOR]

A metal-free strategy has been developed for the α-arylation of carboxylic acids, secondary amides, and esters employing arenes as key reagents. This process entails the Lewis-acid catalyzed reductive Friedel–Crafts alkylation of arenes utilizing α-ketoacids, facilitated by silane in HFIP solvent. The transformation exhibits exceptional functional group tolerance, enabling late-stage functionalization of natural products. This one-step protocol has been successfully used to synthesize commercially available drugs, such as adiphenine, piperidolate, derivatives of ketoprofen, ibuprofen, flurbiprofen, and the pesticide bromopropylate. [ABSTRACT FROM AUTHOR]

Topic: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) for management of pain in patients after photorefractive keratectomy (PRK). Clinical Relevance: Pain after PRK is a major concern for both patients and surgeons. Although evidence supports the use of NSAIDs postoperatively, no consensus exists regarding the preferred regimen. The study aimed to compare the efficacy and safety of different topical NSAIDs. Methods: This study was prospectively registered with PROSPERO (ID: CRD42023417651). A systematic search of electronic databases was performed, for randomized controlled trials reporting topical NSAIDs' outcomes of corneal re-epithelization, rescue analgesics intake, and pain in days 0 to 3 after PRK (postoperative days [PODs] 0 to 3). Studies were graded for risk of bias. Data were extracted, and standardized mean differences (SMDs) were evaluated in a network meta-analysis in accordance with the Cochrane's guidelines, to which a frequentist approach model was fitted. Transitivity was assessed using the net split method. Treatment effectiveness was ranked using forest plots based on comparison with placebo. P-scores (P) and league tables were used to examine combined direct and indirect comparisons. Results: Of 1540 studies identified, 27 were included. These encompassed 2286 patients across 11 countries, evaluating 7 distinct topical NSAIDs. At POD0, ketorolac (P 0.764), flurbiprofen (P 0.763), and bromfenac (P 0.717) were the most efficient drugs overall and displayed significantly lower pain scores than placebo. Other than that, flurbiprofen held the highest rank for reported pain throughout, significantly outperforming placebo on POD1 (P 0.874, SMD -1.19, 95% CI -1.86 to -0.52), POD2 (P 0.882, SMD -1.05, 95% CI -1.82 to -0.27), and POD3 (P 0.939, SMD -1.14, 95% CI -2.1 to -0.18). Other NSAIDs were significantly better than placebo only on POD1 and POD0. Rescue analgesic intake analysis favored indomethacin (P 0.834, SMD-0.8, 95%CI-1.33 to-0.27), ketorolac, and diclofenac. Compared with placebo, re-epithelization was slowed to different significances with all NSAIDs but flurbiprofen (P 0.991, SMD -0.7, 95% CI -1.38 to -0.03). Conclusions: Flurbiprofen was favorable in pain scores on typically painful postoperative days and re-epithelization times. However, analgesics intake, a more objective outcome, suggested superiority of other NSAIDs. Inconsistencies may be explained by the small sample size. For clinical interpretation, NSAID effect sizes should be taken into consideration. [ABSTRACT FROM AUTHOR]

Background/Objectives: For locally applied, locally acting generic drug products, comparison to an originator product based on systemic exposure is usually not feasible due to low plasma concentrations and inadequate reflection of local exposure at the site of action. Where a validated PD model exists, a comparative clinical study can be performed in healthy subjects; where no surrogate endpoint is available, patients with the relevant indication need to be enrolled, with all the associated factors which could result in lack of sensitivity. Even though the need for alternative in vitro approaches has been acknowledged by both industry and regulatory bodies, the complexity of in vivo drug delivery processes makes the development of guidance documents particularly difficult. Our objective was to present in vitro approaches less classically used and to address in vivo relevance of the selected tests. Methods: This article analyses current regulatory approaches in Europe and the U.S., and highlights the key advantages of in vitro tests in terms of their sensitivity, reliability, reproducibility and in vivo relevance using locally applied flurbiprofen in various formulations. Results: The in vitro esophageal retention (IVOR) model demonstrates that the first 6–10 min after application of different flurbiprofen formulations is important for their comparison and also offers the best correlation with in vivo data using the partial area under the concentration-time curves (pAUCs). Rheological evaluations further demonstrated that the mucoadhesive properties of the gel spray formulation are based on interaction with mucin. Conclusions: Designing a relevant in vitro test requires adequate evaluation of the complexity of the drug substance, drug product, dosing conditions and delivery processes. [ABSTRACT FROM AUTHOR]

In order to effectively treat arthritis, this study formulated and evaluated a nanogel containing flurbiprofen and betamethasone. Using ionic gelation technology, nanogels were created by fine-tuning a number of process parameters, such as the concentration of the polymer and cross-linker, as well as the stirring speed, stirring duration, and sonication time. The results demonstrated that the particle size and drug loading efficiency were enhanced as the concentrations of the polymer and cross-linker were increased; the ideal concentrations were 0.4% w/v polymer and 0.4% w/v cross-linker. Particle size was also shown to be greatly affected by stirring duration and speed; particles were found to be smaller while stirring for longer periods of time and faster speeds. Particle size was further reduced to 174.16 nm by sonication for 5 minutes, and the drug loading efficiency was an acceptable 72.02%. The enhanced formulation had a PDI, zeta potential, and particle size distribution that were advantageous, which improved stability and medicine encapsulation. Because it ensures a controlled release of the drug and improves patient outcomes, this nanogel system offers potential as a novel approach to providing anti-inflammatory drugs for the treatment of arthritis. [ABSTRACT FROM AUTHOR]

The frequent use of anti‐inflammatory drugs and the side effects of existing drugs keep the need for new compounds constant. For this purpose, flurbiprofen and ibuprofen‐like compounds, which are frequently used anti‐inflammatory compounds in this study, were synthesized and their structures were elucidated. Like ibuprofen and flurbiprofen, the compounds contain a residue of phenylacetic acid. On the other hand, it contains a secondary amine residue. Thus, it is planned to reduce the acidity, which is the biggest side effect of NSAI drugs, even a little bit. The estimated ADME parameters of the compounds were evaluated. Apart from internal use, local use of anti‐inflammatory compounds is also very important. For this reason, the skin permeability values of the compounds were also calculated. And it has been found to be compatible with reference drugs. The COX enzyme inhibitory effects of the obtained compounds were tested by in vitro experiments. Compound 2a showed significant activity against COX‐1 enzyme with an IC50 = 0.123 + 0.005 μM. The interaction of the compound with the enzyme active site was clarified by molecular dynamics studies. [ABSTRACT FROM AUTHOR]

Abstract Background The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and postoperative acute kidney injury (AKI) remains controversial, with limited studies specifically examining flurbiprofen. Therefore, this research aimed to investigate the association between intraoperative flurbiprofen administration and postoperative AKI. Methods We retrospectively identified a cohort of patients at the Third Xiangya Hospital of Central South University. A total of 3882 adult patients undergoing spinal surgery between January 1, 2012, and July 31, 2018, were included and classified into two groups: those receiving flurbiprofen (50 or 100 mg once, 5 min after anesthesia start) and those not receiving flurbiprofen. The primary endpoint was the incidence of AKI. Result The flurbiprofen group (4.4%) had a lower incidence of AKI compared to the non-flurbiprofen group (6.5%, P

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]

As a selective and potent inhibitor targeting the isocitrate dehydrogenase‐2 (IDH2) mutant protein, enasidenib obtained approval from the US Food and Drug Administration (FDA) in 2017 for adult patients with acute myeloid leukemia (AML) with an IDH2 mutation. In vitro investigations demonstrated that enasidenib affects various drug metabolic enzymes and transporters. This current investigation aimed to assess enasidenib on the pharmacokinetics (PKs) of CYP substrates, including dextromethorphan (CYP2D6 probe drug), flurbiprofen (CYP2C9 probe drug), midazolam (CYP3A4 probe drug), omeprazole (CYP2C19 probe drug), and pioglitazone (CYP2C8 probe drug), in patients with AML or myelodysplastic syndrome. Results showed that following the co‐administration of enasidenib (100 mg, once daily) for 28 days, the PK parameters AUC(0‐∞) and Cmax of dextromethorphan increased by 1.37 (90% confidence interval (CI): 0.96, 1.96) and 1.24 (90% CI: 0.94, 1.65)‐fold, respectively, compared to dextromethorphan alone. For flurbiprofen, these parameters increased by 1.14 (90%CI: 1.01, 1.29) and 0.97 (90% CI 0.86, 1.08)‐fold, respectively, when compared to flurbiprofen alone. Conversely, midazolam exhibited decreases to 0.57 (90% CI 0.34, 0.97) and 0.77 (90% CI 0.39, 1.53)‐fold, respectively, in comparison to midazolam alone. The parameters for omeprazole increased by 1.86 (90% CI: 1.33, 2.60) and 1.47 (0.93, 2.31)‐fold, respectively, compared to omeprazole alone, while those for pioglitazone decreased to 0.80 (90% CI: 0.62, 1.03) and 0.87 (90% CI: 0.65, 1.16)‐fold, respectively, in comparison to pioglitazone alone. These findings provide valuable insights into dose recommendations concerning drugs acting as substrates of CYP2D6, CYP2C9, CYP3A4, CYP2C19, and CYP2C8 when administered concurrently with enasidenib. [ABSTRACT FROM AUTHOR]

Background and Aims: This investigation aimed to enhance flurbiprofen’s (FB) pre-corneal residence period and ocular availability in the postoperative management of ocular inflammation. Methods: The microsphere (MS) material was poly (lactic-co-glycolic acid) PLGA, and FB-laden microspheres were prepared using a single emulsification/solvent evaporation process, loaded onto thermosensitive in situ gels, and then characterised. Results: The size of the microparticles was measured as 19.3±2.1 μm. Entrapment efficiency, zeta potential, and in vitro release; it was observed that the microspheres were released for six days. The optimum gelling capacity was obtained using 15% Poloxamer 407, 8% Poloxamer 188, and 1% HEC (viscosity 80-125 cp). Poloxamer 407 concentration was reduced, resulting in increased gelation temperature and duration. It was determined that the gelling temperature of the selected formulation was 35±0.1 °C, the pH was 6.9±0.02, and the viscosity at the gelling temperature was 11042±247 cP. The addition of hydroxyethyl cellulose increased the mucoadhesive strength. - in vitro release of FB from FB-PLGA MS followed the Korsmeyer-Peppas model, –, and the in situ gel preparation was found to be compatible with the Peppas-Sahlin model. In addition, MTT analysis of the ARPE-19 cell line revealed that the in situ gel formulation was biocompatible. Conclusion: Flurbiprofen release was sustained, ocular availability was improved, and residence time was increased when flurbiprofen-loaded microspheres were incorporated into in situ gel bases. [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]

Background: The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and postoperative acute kidney injury (AKI) remains controversial, with limited studies specifically examining flurbiprofen. Therefore, this research aimed to investigate the association between intraoperative flurbiprofen administration and postoperative AKI. Methods: We retrospectively identified a cohort of patients at the Third Xiangya Hospital of Central South University. A total of 3882 adult patients undergoing spinal surgery between January 1, 2012, and July 31, 2018, were included and classified into two groups: those receiving flurbiprofen (50 or 100 mg once, 5 min after anesthesia start) and those not receiving flurbiprofen. The primary endpoint was the incidence of AKI. Result: The flurbiprofen group (4.4%) had a lower incidence of AKI compared to the non-flurbiprofen group (6.5%, P < 0.001). After adjusting for potential confounding variables, the multivariable regression analysis showed that the flurbiprofen group had a 49% reduced risk of postoperative AKI (OR 0.51; 95% CI 0.31 to 0.82) compared to the non-flurbiprofen group. Subgroup analysis indicated that flurbiprofen injection was associated with a reduced incidence of postoperative AKI in patients without diabetes (OR 0.61; 95% CI 0.19 to 0.74), surgical times of 2–5 h (OR 0.54; 95% CI 0.23 to 0.75), and preoperative anemia (OR 0.57; 95% CI 0.21 to 0.74). Conclusion: The study concluded that perioperative flurbiprofen treatment was associated with a lower risk of postoperative AKI in adult patients undergoing spinal surgery. [ABSTRACT FROM AUTHOR]

Herpes stromal keratitis (HSK) is an immune-mediated corneal inflammation that occurs after a herpes simplex virus infection. This paper aims to systematically identify and compare interventions for treating HSK and their patient outcomes. This systematic review followed the PRISMA methodology. Online databases were searched to obtain all relevant papers. Two independent reviewers screened through 168 records. Seven papers were included and used for data extraction. A qualitative analysis was conducted. HSK patients receiving prednisolone phosphate and acyclovir showed a higher treatment success rate and significantly longer time to failure compared to patients receiving only acyclovir (P <.001). No difference in resolution time was found between oral and topical acyclovir. Between groups receiving dexamethasone and flurbiprofen, resolution occurred in 93% and 67% of patients, and BCVA (LogMAR) improved from 1.0 to 0.30 and 0.48, respectively. BCVA improved in both cyclosporine-A (P <.001) and its control (prednisolone) groups (P =.002). A tacrolimus treatment group showed greater improvement in BCVA compared to its control (prednisolone) group (P <.001). Corticosteroids and antivirals managed HSK most effectively only when used concurrently. Oral acyclovir showed similar effectiveness to its ointment counterpart, a preferable alternative for easier administration. Corticosteroid use could induce greater therapeutic benefits when tapered in concentration and frequency and administrated for at least 10 weeks. Anti-inflammatory drugs including flurbiprofen, cyclosporine-A, and tacrolimus could be safe and effective for treating HSK. Future long-term follow-up and RCTs could provide insights on the therapeutic benefits of these potential alternatives. [ABSTRACT FROM AUTHOR]

Drugs that are poorly soluble in water are difficult to absorb orally, resulting in low bioavailability. Flurbiprofen (FLU) is an arylpropionic acid nonsteroidal anti‐inflammatory drug belonging to BCS class II, with low water solubility. In this study, a novel flurbiprofen‐ethylenediamine salt (FLU‐EDA) was successfully prepared via solvent crystallization. Its crystal structure was determined via single‐crystal X‐ray diffraction (SXRD). Further, the physicochemical properties of FLU‐EDA salt were characterized by powder X‐ray diffraction (PXRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT‐IR). The solubility and intrinsic dissolution rate (IDR) of FLU‐EDA salt in water were investigated. The results showed that compared with FLU, the solubility and IDR of FLU‐EDA salt increased by 57‐fold and 32‐fold, respectively. This indicates that FLU‐EDA salt can significantly enhance the solubility and dissolution rate of flurbiprofen in water. This study provides basic data and theory for the development of new formulations of flurbiprofen. [ABSTRACT FROM AUTHOR]

Flurbiprofen (FB), a nonsteroidal anti-inflammatory drug, is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects. However, the racemic nature of its commercially available formulation (Ocufen®) limits the full potential of its therapeutic activity, as the (S)-enantiomer is responsible for the desired antiinflammatory effects. Additionally, the limited corneal permeability of FB significantly restricts its bioavailability. In this study, we successfully separated the chiral isomers of FB to obtain the highly active (S)-FB. Subsequently, utilizing ion-pairing technology, we coupled (S)-FB with various counter-ions, such as sodium, diethylamine, trimethamine (TMA), and l-arginine, to enhance its ocular bioavailability. A comprehensive evaluation encompassed balanced solubility, octanol-water partition coefficient, corneal permeability, ocular pharmacokinetics, tissue distribution, and in vivo ocular anti-inflammatory activity of each chiral isomer salt. Among the various formulations, S-FBTMA exhibited superior water solubility (about 1-12 mg/ml), lipid solubility (1 < lg Pow < 3) and corneal permeability. In comparison to Ocufen®, S-FBTMA demonstrated significantly higher in vivo antiinflammatory activity and lower ocular irritability (such as conjunctival congestion and tingling). The findings from this research highlight the potential of chiral separation and ion-pair enhanced permeation techniques in providing pharmaceutical enterprises focused on drug development with a valuable avenue for improving therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Nanocomposite gels consist of nanoparticles dispersed in a gel matrix. The main aim of this work was to develop nanocomposite gels for topical delivery of Flurbiprofen (FB) for humans and farm animals. Nanocomposite gels were prepared stemming from nanoparticles (NPs) freeze-dried with two different cryoprotectants, D-(+)-trehalose (NPs-TRE) and polyethylene glycol 3350 (NPs-PEG), sterilized by gamma (γ) irradiation, and gelled with Sepigel® 305. Nanocomposite gels with FB-NPs-TRE and FB-NPs-PEG were physiochemically characterized in terms of appearance, pH, morphological studies, porosity, swelling, degradation, extensibility, and rheological behavior. The drug release profile and kinetics were assessed, as well as, the ex vivo permeation of FB was assessed in human, porcine and bovine skin. In vivo studies in healthy human volunteers were tested without FB to assess the tolerance of the gels with nanoparticles. Physicochemical studies demonstrated the suitability of the gel formulations. The ex vivo skin permeation capacity of FB-NPs nanocomposite gels with different cryoprotectants allowed us to conclude that these formulations are suitable topical delivery systems for human and veterinary medicine. However, there were statistically significant differences in the permeation of each formulation depending on the skin. Results suggested that FB-NPs-PEG nanocomposite gel was most suitable for human and porcine skin, and the FB-NPs-TRE nanocomposite gel was most suitable for bovine skin. [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]

Abstract The aim of this randomized clinical study was to assess the comparative efficacy of flurbiprofen in tablet and spray formulations for postoperative pain management in oral soft tissue wounds undergoing primary closure while investigating the feasibility of achieving optimal analgesia with reduced dosage and risk. Forty patients who underwent epulis fissuratum and frenulum excision for pre-prosthetic surgery were randomly assigned to receive either tablet or spray forms of flurbiprofen. The lesion dimensions were measured preoperatively, followed by excision and primary closure. The tablet group received oral tablets containing 100 mg of flurbiprofen twice daily, whereas the spray group received an oral spray containing 0.25% flurbiprofen, administered as two sprays thrice daily. Postoperative pain was assessed using the Numerical Rating Scale (NRS) until the 7th day. Lesion size, drug consumption, and rescue analgesic use were compared between the groups. There were no statistically significant differences in the lesion size between the groups. However, the mean NRS score in the spray group was significantly lower in the spray group compared to than that in the tablet group at 6th hour postoperatively (p = 0.037). Significant differences favoring the tablet group were observed in the first three doses of the drug (p = 0.001). No patients required rescue analgesics. The spray formulation of flurbiprofen demonstrated effective and safe pain relief in oral soft tissue wounds undergoing primary closure, with no reported adverse effects.

This research is based on the synthesis, characterization and in vitro α‐glucosidase inhibitory activity of fourteen amides (2 a–2 n) of flurbiprofen drug. Seven compounds in the series displayed potent inhibitory activity having IC50 values (IC50=5.67±0.89 μM) to (IC50=17.87±2.39 μM) in comparison with acarbose standard (IC50=875.75±1.24 μM). The FMO of 2 a–2 n molecules was quantified by the DFT assay. The promising value for energygap explained the higher poteny agannist α‐glucosidase. MEP provides the insights into the distribution of electrostatic potential on the molecular surface of 2 a–2 n, showing that C=O group has the highest negative potential. The AIM investigation revealed minimal hydrogen bond energy and non‐covalent interactions. This suggests that these molecules may have limited hydrogen bonding and non‐covalent interactions, which could be relevant to their chemical behavior. Molecular docking and (MEP) showed the C=O group, with its high negative potential, is a key in recognizing the catalytic non‐polar regions of enzymes, such as TYR72, GLU277, and ARG442. Similarly, the hydrophobic regions of investigated compounds play a significant role in identifying essential amino acids like ASP352 and ARG442, which are vital for the ligand's proper orientation and subsequent biological activity. [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]

In this study, we aimed to develop thermosensitive and bioadhesive in situ gelling systems containing solid dispersions of flurbiprofen (FB-SDs) using poloxamer 407 (P407) and 188 (P188) for ophthalmic delivery. FB-SDs were prepared with the melt method using P407, characterized by solubility, stability, SEM, DSC, TGA, and XRD analyses. Various formulations of poloxamer mixtures and FB-SDs were prepared using the cold method and P407/P188 (15/26.5%), which gels between 32 and 35 °C, was selected to develop an ophthalmic in situ gelling system. Bioadhesive polymers Carbopol 934P (CP) or carboxymethyl cellulose (CMC) were added in three concentrations (0.2, 0.4, and 0.6% (w/w)). Gelation temperature and time, mechanical properties, flow properties, and viscosity values were determined. The in vitro release rate, release kinetics, and the release mechanism of flurbiprofen (FB) from the ophthalmic formulations were analyzed. The results showed that FB-SDs' solubility in water increased 332-fold compared with FB. The oscillation study results indicated that increasing bioadhesive polymer concentrations decreased gelation temperature and time, and formulations containing CP gel at lower temperatures and in a shorter time. All formulations except F3 and F4 showed Newtonion flow under non-physiological conditions, while all formulations exhibited non-Newtonion pseudoplastic flow under physiological conditions. Viscosity values increased with an increase in bioadhesive polymer concertation at physiological conditions. Texture profile analysis (TPA) showed that CP-containing formulations had higher hardness, compressibility, and adhesiveness, and the gel structure of formulation F4, containing 0.6% CP, exhibited the greatest hardness, compressibility, and adhesiveness. In vitro drug release studies indicated that CP and CMC had no effect below 0.6% concentration. Kinetic evaluation favored first-order and Hixson–Crowell kinetic models. Release mechanism analysis showed that the n values of the formulations were greater than 1 except for formulation F5, suggesting that FB might be released from the ophthalmic formulations by super case II type diffusion. When all the results of this study are evaluated, the in situ gelling formulations prepared with FB-SDs that contained P407/P188 (15/26.5%) and 0.2% CP or 0.2% CMC or 0.4 CMC% (F2, F5, and F6, respectively) could be promising formulations to prolong precorneal residence time and improve ocular bioavailability of FB. [ABSTRACT FROM AUTHOR]

Background: Flurbiprofen 8.75 mg lozenges and oromucosal sprays are used for symptomatic relief of sore throat in patients aged 12 years and over. The documented adverse events of flurbiprofen use include those related to its pharmacological actions, namely, increased risk of haemorrhagic events, however other adverse events (such as nephrotoxicity and cardiac failure) have been known to occur. The likelihood of occurrence of adverse events increases when flurbiprofen is used concomitantly with some other medications. Therefore, the objective of this systematic review was to collate the current evidence on adverse events which occur with flurbiprofen 8.75 mg dose (any formulation), in particular as a result of interaction with other medicinal products, with a focus on non-haemorrhagic events. Methods: Systematic searches of the literature were conducted to identify literature on any formulation of flurbiprofen 8.75 mg up to the date of the electronic database search (data lock: 28 April 2020). Publications were screened to identify studies reporting non-haemorrhagic adverse events with flurbiprofen 8.75 mg and/or non-haemorrhagic adverse events in the comparator arm. Data extraction was performed for eligible studies according to pre-defined criteria and summarised in narratives, tables and figures. Risk of bias and certainty of evidence assessments were planned for each included study where results relating to the primary objective of the systematic review were available. Results: Of 1,528 publications identified by systematic literature searches, 26 met the inclusion criteria and were included in this review. None of these 26 studies contained information on non-haemorrhagic adverse events occurring as a result of a drug-drug interaction (interaction with concomitant medication used with flurbiprofen 8.75 mg), as per the primary objective and secondary objectives of the systematic review. Conclusion: Results from this systematic review on the risk of non-haemorrhagic events did not provide evidence for these events occurring as a result of interaction with other medicinal products. Additional appropriately designed studies would be required to confirm whether these findings suggest a true absence of risk or limitations in reporting. [ABSTRACT FROM AUTHOR]