This pilot study aimed to explore the effectiveness and safety of dexibuprofen suppository in the treatment of PDA in preterm infants. Preterm infants with gestational age <34 weeks and color Doppler echocardiographic evidence of hemodynamically significant PDA (hs PDA) with systemic hypoperfusion was intended to be included into this study since January 2020. As of January 1, 2021, this trial had recruited 87 preterm infants who met the inclusion criteria. Neonates were admitted into hospital within 1 hour after birth and were randomly assigned into two groups. Group one included 44 preterm newborns administered with oral ibuprofen. Group two included 43 preterm newborns administered with dexibuprofen suppository. This preliminary study showed that rectal dexibuprofen and oral ibuprofen were both effective for the closure of PDA, and the closure rate of dexibuprofen suppository was comparable to that of oral ibuprofen after the 1st and 2nd courses of treatment. In addition, rectal dexibuprofen did not increase the incidence of adverse outcomes, including bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and necrotising enterocolitis. This pilot study showed dexibuprofen suppository is as effective and safe as oral ibuprofen; yet, better designed, muticenter controlled studies are still needed.

Combinations of drugs may be fixed (two or more entities in a single product) or loose (two or more agents taken together but as individual agents) to help address multimechanistic pain. The use of opioids plus nonopioids can result in lower opioid consumption without sacrificing analgesic benefits. Drug combinations may offer additive or synergistic benefits. A variety of fixed-dose combination products are available on the market such as diclofenac plus thiocolchicoside, acetaminophen and caffeine, acetaminophen and opioid, ibuprofen and acetaminophen, tramadol and acetaminophen, and others. Fixed-dose combination products offer predictable pharmacokinetics and pharmacodynamics, known adverse events, and can reduce the pill burden. However, they are limited to certain drug combinations and doses; loose dosing allows prescribers the versatility to meet individual patient requirements as well as the ability to titrate as needed. Not all drug combinations offer synergistic benefits, which depend on the drugs and their doses. Certain drugs offer dual mechanisms of action in a single molecule, such as tapentadol, and these may further be used in combination with other analgesics. New technology allows for co-crystal productions of analgesic agents which may further improve drug characteristics, such as bioavailability. Combination analgesics are important additions to the analgesic armamentarium and may offer important benefits at lower doses than monotherapy.

Ibuprofen is potentially toxic and carcinogenic for freshwater ecosystems and poses a serious threat to human health by affecting kidney function. The present study focused on the sunlight-controlled degradation of ibuprofen from water using a novel magnetically separable cerium oxide-embedded bismuth ferrite heterostructure. Catalysts were synthesized by solvothermal and co-precipitation methods and characterized by X-ray diffractometry, transmission electron microscopy, X-ray photoelectron spectroscopy, UV-vis optical absorption spectroscopy, and nitrogen adsorption. This study investigated the effect of photocatalysis, sonolysis, sonophotolysis, and sonophotocatalysis on the degradation of ibuprofen in water. Pseudo-first-order and second-order kinetics were applied to evaluate the rate of reaction for ibuprofen degradation. The addition of 5% CeO2 to the BiFeO3 significantly increased the surface area and pore volume of bismuth ferrite, which enhanced their photocatalytic degradation efficiency by 2.28 times in terms of ibuprofen mineralization. Sonolysis treatment alone and in combination with photolysis led to the degradation of ibuprofen, but with the formation of intermediate products. Positive synergy was observed when sonolysis was combined with photocatalysis in terms of the mineralization of ibuprofen and the degradation of intermediates along with their parent compound. It was proposed that, compared to photocatalytic mineralization, the ultrasound-assisted advanced oxidation process resulted in the conversion of ibuprofen to its mineralization products.

An in-depth understanding of the properties of gastric fluid(s) prior to an in vivo pharmacokinetic investigation can vastly improve predictions of in vivo performance. Previously, properties of animal and human gastric fluids have been characterized with varying methods. Unfortunately, characterization has often not been thorough, and some properties, such as density and viscosity, have not been reported. Here, human, porcine and canine gastric fluids were harvested and characterized for pH, viscosity, surface tension, density, and osmolarity. We found that the variability of pH and surface tension between dogs was significantly higher than the variability between pigs, and, furthermore, gastric fluids collected from the same canine species (beagles) housed in two different countries (Denmark and China) had surprisingly different pH values. Next, an in vitro dissolution study in diluted gastric fluids from each species was performed using minitablets containing ibuprofen. Human gastric fluids and porcine gastric fluids showed similar dissolution profiles and corroborated well with biorelevant human Fasted State Simulated Gastric Fluid (FaSSGF). In contrast, differences in canine gastric fluids caused highly variable dissolution results. We systematically compared our findings to those in the literature and based on this evaluation, propose obtaining aspirates from the animals used for in vivo studies to ensure knowledge on the fluid properties affecting the performance of the formulated drug in question.

In this study, titanium oxide nanoparticle was fabricated using the extract of grape leaves (referred asGL-TiO2 NPs), using the green synthesis process, and then explores its ability for photodegradation of ibuprofen (IBU) under UV light in the batch system. UV-Vis, BET, FTIR, XRD, and SEM-EDX tests were made to identify the catalyst's structure and shape. Moreover, the effects of different operating parameters, specifically pH of (3, 5, 7, and 9), IBU concentration (10, 20, 40, and 80) mg/L, GL-TiO2 concentrations (15, 30, and 60) mg/L, H2O2 (100, 300, and 500) mg/L, and contact time were studied. According to the results, the synthetic TiO2 NPs have a spherical shape and 39.608 m2/g of BET surface area. In addition, the findings showed that the removal efficiency reached 92.32% under optimum conditions of 5, 10 mg/L, 30 mg/L, 300 mg/L, and 150 min, respectively. In addition, the reaction followed a first-order kinetics model with R2 ˃97. According to the finding of this study, GL-TiO2 NPs has an acceptable efficiency in the elimination of IBU, as their relatively simple synthesis, could be a suitable catalyst for the degradation and elimination of pharmaceutical residues.

This study aimed to evaluate the bitterness of famotidine (FAM) combined with each of three non-steroidal anti-inflammatory drugs (NSAIDs): ibuprofen (IBU), flurbiprofen (FLU), and naproxen (NAP), which have potential as fixed-dose combination (FDC) drugs. We evaluated the bitterness of FAM and each NSAID by taste sensor AN0 and C00, respectively. FAM showed high sensor output representing sensitivity to bitterness, whereas three NSAIDs did not show large sensor output, suggesting that the bitterness intensities of three NSAIDs were lower than that of FAM. The bitterness of FAM on sensor AN0 was suppressed in a concentration-dependent manner when mixed with IBU, FLU, or NAP. Among three NSAIDs, IBU most effectively inhibited bitterness on sensor output, and the gustatory sensation test confirmed that adding IBU to FAM reduced the bitterness of FAM in a concentration-dependent manner. MarvinSketch confirmed that the drugs were mostly present in an ionic solution when FAM was mixed with NSAIDs. The 1H-NMR spectroscopy analysis also revealed the presence of electrostatic interactions between FAM and NSAIDs, suggesting that the electrostatic interaction between FAM and NSAIDs might inhibit the adsorption of FAM on the bitter taste sensor membrane, thereby masking the bitter taste.

The rich variety of patterns induced by evaporating drops containing particles has significant guidance for coating processes, inkjet printing, and nanosemiconductors. However, most existing works construct a uniform pattern by suppressing the coffee ring effect, and establishing the connection between them is still an academic challenge.

This article discusses a new method for the preparation of extemporaneous ibuprofen-based suspensions for use in paediatric patients. This method allows the preparation of extemporaneous suspensions up to concentrations of 200 mg/5 mL by using a liquid base named "Wagner." A comprehensive physicochemical stability study was conducted on the formulation at a drug concentration of 200 mg/5 mL by performing high-pressure liquid chromatography and Turbiscan analyses. Chromatographic analyses of the samples demonstrated the chemical stability of the active pharmaceutical ingredient in the base for more than 90 days when the formulations were stored at 4°C and 25°C. Visual and optical analyses evidenced a reversible, slightly creaming phenomenon when the formulations were stored at 4°C or 25°C restoring the initial suspension by simply shaking.

The objective of this study was to prepare and evaluate ibuprofen nanocrystals using isopropyl alcohol and stabilizer sodium lauryl sulphate by way of the precipitation method. The nanocrystals were prepared by the bottom-up approach of the precipitation technique. This technique involves the use of an organic phase, which is completely miscible in the external aqueous phase. The ratio used for organic solvent-to-aqueous solvent was 1:50. The Fourier Transform Infrared Spectroscopy analyses confirmed that the drug and excipients were compatible, and the differential scanning calorimetry results indicated that the precipitation method led to no change in the crystalline structure of the drug. Scanning electron microscopy analysis of ibuprofen nanocrystals showed the promising size reduction of pure drug ibuprofen. Differential light scattering technique showed significant decrease in particle size and good stability of ibuprofen nanocrystals. Ibuprofen nanocrystals increased 20% to 25% of the saturation solubility of ibuprofen nanocrystals. Ibuprofen nanocrystals showed 90% drug release in the dissolution medium within 1 hour, while the pure drug and market product were dissolved only up to 58% and 63%, respectively. Ibuprofen nanocrystals increased the saturation solubility and in vitro dissolution of the drug as compared to conventional market product.

Drug repurposing is a strategy used to develop new treatments based on approved or investigational drugs outside the scope of their original clinical indication. Since this approach benefits from the original toxicity data of the repurposed drugs, the drug-repurposing strategy is time-saving, and inexpensive. It has a higher success rate compared to traditional drug discovery. Several repurposing candidates have been identified in silico screening and in vitro methodologies. One of the best examples is non-steroidal anti-inflammatory drugs [NSAIDs]. Tumor-promoting inflammation is one of the hallmarks of cancer, revealing a connection between inflammatory processes and tumor progression and development. This explains why using NSAIDs in the context of neoplasia has become a topic of interest. Indeed, identifying NSAIDs with antitumor activity has become a promising strategy for finding novel cancer treatment opportunities. Indeed, several commercial anti-inflammatory drugs, including aspirin, ibuprofen, diclofenac, celecoxib, tepoxalin and cyclovalone, naproxen, and indomethacin have presented antitumor activity, and some of them are already in clinical trials for cancer treatment. However, the benefits and complications of using NSAIDs for cancer treatment must be carefully evaluated, particularly for cancer patients with no further therapeutic options available. This review article provides insight into the drug repurposing strategy and describes some of the well-known NSAIDs that have been investigated as repurposed drugs with potential anticancer activity.

Globally, the prevalence and pollution of pharmaceutical drugs in aquatic environments have been steadily increasing. This study sought to evaluate the effects of 14 days of exposure to environmental-relevant doses (ibuprofen 0.5, 5, and 50 µg/L, and carbamazepine 0.005, 1, and 10 µg/L) of the nonsteroidal anti-inflammatory drugs ibuprofen and carbamazepine in the freshwater fish Oreochromis mossambicus. The results showed a significant (P < 0.05) decrease in O. mossambicus superoxide dismutase, catalase, biotransformation enzymes, glutathione-s-transferase, glutathione peroxidase, oxidative stress lipid peroxidation, protein carbonyl activity, cellular damage metallothionine, reduced glutathione, immunological activities, and respiratory burst activity. Consequently, the acquired data revealed that O. mossambicus treated with ibuprofen and carbamazepine shows more significant alterations in metabolic depression, biochemical parameters, and oxidative stress. In addition, increased neurotoxic effects were observed in ibuprofen and carbamazepine treated O. mossambicus.

The interaction between the plasma protein bovine serum albumin (BSA) and the drug ibuprofen (IBU) has been investigated at three different pH values (7.4, 6.5, and 8.0) in the presence of oligosaccharides and surfactants. The interaction analysis of BSA with oligosaccharides and surfactants has also been studied in the absence of the drug ibuprofen. The results obtained give convenient and efficient access to understand the mechanism of binding of ibuprofen to BSA, and the major forces involved are found to be hydrophobic forces, hydrogen bonding and ionic interactions. In addition to that, the formation of inclusion complexes of ibuprofen with oligosaccharides (β-CD and 2-HP-β-CD) has been observed, which has depicted that due to the hydrophobic nature of ibuprofen, it becomes more soluble in the presence of oligosaccharides, but due to the larger size of the inclusion complexes, these could not be able to access the hydrophobic pocket of BSA where tryptophan-212 (Trp-212) resides. The binding interaction between BSA and ibuprofen is observed in the presence of surfactants (SDS and CTAB), which partially unfold the protein. Non-radiative fluorescence resonance energy transfer (FRET) from Trp and Tyr residues of BSA in the presence of an anionic surfactant SDS to ibuprofen has depicted that there is a possibility of drug binding even in the partially unfolded state of BSA protein. Furthermore, the distance between the protein and the drug has been calculated from the FRET efficiency, which gives a comprehensive overview of ibuprofen binding to BSA even in its partially denatured state. The hydrophobic drug binding to the partially unfolded serum albumin protein (BSA) supports the "necklace and bead structures" model and opens up a new direction of drug loading and delivery system, which will have critical therapeutic applications in the efficient delivery of pharmacologically prominent drugs.

Opioid minimization in the acute postoperative phase is timely in the era of the opioid epidemic. The authors hypothesize that patients with facial trauma receiving multimodal, narcotic-minimizing pain management in the perioperative period will consume fewer morphine milligram equivalents (MMEs) while maintaining adequate pain control compared with a traditional analgesia protocol. An IRB-approved pilot study evaluating isolated facial trauma patients compared 10 consecutive prospective patients of a narcotic-minimizing pain protocol beginning in August 2020 with a retrospective, chart-reviewed cohort of 10 consecutive patients before protocol implementation. The protocol was comprised of multimodal nonopioid pharmacotherapy given preoperatively (acetaminophen, celecoxib, and pregabalin). Postoperatively, patients received intravenous (IV) ketorolac, scheduled acetaminophen, ibuprofen, and gabapentin. Oxycodone was reserved for severe uncontrolled pain. The control group had no standardized protocol, though opioids were ad libitum. Consumed MMEs and verbal Numeric Rating Scale (vNRS) pain scores (0-10) were prospectively tracked and compared with retrospective data. Descriptive and inferential statistics were run. At all recorded postoperative intervals, narcotic-minimizing subjects consumed significantly fewer MMEs than controls [0-8 h, 21.5 versus 63.5 (P = 0.002); 8-16 h, 4.9 versus 20.6 (P = 0.02); 16-24 h, 3.3 versus 13.9 (P = 0.03); total 29.5 versus 98.0 (P = 0.003)]. At all recorded postoperative intervals, narcotic-minimizing subjects reported less pain (vNRS) than controls (0-8 h, 7.7 versus 8.1; 8-16 h, 4.4 versus 8.0; 16-24 h 4.3 versus 6.9); significance was achieved at the 8 to 16-hour time point (P = 0.006). A multimodal, opioid-sparing analgesia protocol significantly reduces opioid use in perioperative facial trauma management without sacrificing satisfactory pain control for patients.

Pain is one of the most common reasons for seeking medical intervention, and self-medication with over-the-counter medications and/or traditional herbal remedies has become increasingly popular. In this review, original articles on understanding possible herb-drug interaction between traditional herbs and four major pain medication: acetaminophen, aspirin, ibuprofen, and naproxen were compiled and analyzed. In terms of analytical methods, high-performance liquid chromatography using an isocratic eluent system coupled to biological sample clean-up is the most common, while a wide variety of detectors have been observed, including a photo diode array, variable wavelength detector, electrochemical detector, and tandem mass spectrometer. Both synergistic and anti-synergistic effects were observed for acetaminophen and aspirin, while only synergistic effects have been found for naproxen. Currently, no interactions have been reported for ibuprofen.

Septic systems are widely used in rural areas that lack centralized sewage treatment systems. Incomplete removal of domestic wastewater contaminants in septic systems can lead to leaching of nutrients (P and N), bacteria/viruses, and trace contaminants to surrounding groundwater and surface water. This study focuses on delineating the fate of wastewater contaminants in localities in which septic systems are installed in moderate to fine-grained overburden materials to assess potential impacts on groundwater and surface water quality in these settings. Nutrients and a suite of anthropogenic tracers, including host-specific fecal indicator bacteria (bovine- and human-specific Bacteroides), pharmaceutical compounds (caffeine, carbamazepine, gemfibrozil, ibuprofen, naproxen, and sulfamethoxazole), and an artificial sweetener (acesulfame-K), were selected to evaluate differences in transport properties. Surface water samples (n = 103) were collected from streams upstream (US) and downstream (DS) of three rural hamlets up to two times monthly over one year. Results indicate the presence of wastewater indicators in the streams, with DS locations showing significantly elevated concentrations of both chemical and biological anthropogenic tracers. Human-specific Bacteroides, caffeine, and acesulfame-K were consistently observed at elevated concentrations at all DS sites. Nutrients exhibited varied concentrations between US and DS locations at three study sites. The occurrence of human-specific Bacteroides in the surface water samples suggests the presence of preferential flow pathways within the silt/clay overburden. These results demonstrate the advantages of using a combined tracer approach, involving a conservative tracer such as acesulfame-K coupled with the human-specific biological indicator Bacteroides (BacHum), to understand not only impacting sources but also potential transport pathways of septic system contamination to nearby streams. Septic systems may be an underappreciated contaminant source in rural hamlets located in fine-grained overburden materials; although, a distinction of specific nutrient sources (septic systems vs. agriculture) remains challenging.

Coronaviruses (CoVs) infect a broad range of hosts, including humans and various animals, with a tendency to cross the species barrier, causing severe harm to human society and fostering the need for effective anti-coronaviral drugs. GS-441524 is a broad-spectrum antiviral nucleoside with potent anti-CoVs activities. However, its application is limited by poor oral bioavailability. Herein, we designed and synthesized several conjugates via covalently binding NSAIDs to 5'-OH of GS-441524 through ester bonds. The ibuprofen conjugate, ATV041, exhibited potent in vitro anti-coronaviral efficacy against four zoonotic coronaviruses in the alpha- and beta-genera. Oral-dosed ATV041 resulted in favorable bioavailability and rapid tissue distribution of GS-441524 and ibuprofen. In MHV-A59 infected mice, ATV041 dose-dependently decreased viral RNA replication and significantly reduced the proinflammatory cytokines in the liver and the lung at 3 dpi. As a result, the MHV-A59-induced lung and liver inflammatory injury was significantly alleviated. Taken together, this work provides a novel drug conjugate strategy to improve oral PK and offers a potent anti-coronaviral lead compound for further studies.

The current research is focused on investigating the suitability of the twin screw melt granulation (TSMG) approach for improving the solubility of a non-steroidal anti-inflammatory (NSAIDs) drug (ibuprofen), by developing granules using lipid surfactants. The solubility of the drug within the solid lipid excipients (Gelucire® 48/16 and Gelucire® 50/13) was determined by differential scanning calorimetry (DSC). The formulations were developed for drug and lipid ratios of 1:1.5, 1:3, and 1:4.5 using Neusilin® US2 as a solid adsorbent carrier. The solid-state properties of the drug investigated using differential scanning calorimetry (DSC) have revealed the conversion of the drug to an amorphous form for 1:3 and 1:4.5 ratios of formulations confirmed by powder x-ray diffraction analysis (PXRD). Drug-excipient compatibility and formation of no interactions were characterized using Fourier transform infrared spectroscopy (FTIR). The granules with a 1:3 and 1:4.5 ratios of drug and lipid have improved drug dissolution and permeation, attributing to the formation of micellar emulsions. The stability of formulation with a 1:3 ratio of drug and lipid surfactant was preserved when stored in accelerated conditions. However, the formulation with a 1:4.5 ratio of drug and lipid failed to retain the amorphous state evidenced by the recrystallization of the drug. This shows the suitability of TSMG as a single-step continuous manufacturing process for developing melt granules to improve the solubility of poorly water-soluble drug substances.

Destruction of cochlear hair cells by aminoglycoside antibiotics leads to gradual death of the spiral ganglion neurons (SGNs) that relay auditory information to the brain, potentially limiting the efficacy of cochlear implants. Because the reasons for this cochlear neurodegeneration are unknown, there are no neuroprotective strategies for patients. To investigate this problem, we assessed transcriptomic changes in the rat spiral ganglion following aminoglycoside antibiotic (kanamycin)-induced hair cell destruction. We observed selectively increased expression of immune and inflammatory response genes and increased abundance of activated macrophages in spiral ganglia by postnatal day 32 in kanamycin-deafened rats, preceding significant SGN degeneration. Treatment with the anti-inflammatory medications dexamethasone and ibuprofen diminished long-term SGN degeneration. Ibuprofen and dexamethasone also diminished macrophage activation. Efficacy of ibuprofen treatment was augmented by co-administration of the nicotinamide adenine dinucleotide-stabilizing agent P7C3-A20. Our results support a critical role of neuroinflammation in SGN degeneration after aminoglycoside antibiotic-mediated cochlear hair cell loss, as well as a neuroprotective strategy that could improve cochlear implant efficacy.

Anxiety and epilepsy affect millions of people worldwide, and the treatment of these pathologies involves the use of Benzodiazepines, drugs that have serious adverse effects such as dependence and sedation, so the discovery of new anxiolytic and antiepileptic drugs are necessary. Many routes for synthesizing ibuprofen derivatives have been developed, and these derivatives have shown promising pharmacological effects. Therefore, this study aims to evaluate its anxiolytic and anticonvulsant effect against the adult Zebrafish animal model of Ibuprofen (IBUACT) and its interaction with the GABAergic receptor through in silico studies. The light/dark preference test (Scototaxis test) was used to evaluate the anxiolytic behavior of adult Zebrafish acutely treated with IBUACT and Diazepam, and their anticonvulsant effects were investigated through the pentylenetetrazol (PTZ)-induced seizure model. Animals treated with IBUACT showed anxiolytic behavior similar to Diazepam, and pretreatment with flumazenil reversed this behavior. PTZ-induced seizures were delayed by IBUACT in all three stages and were shown to bind strongly in the Diazepam region of GABAA. In addition, this work presents evidence of new pharmacological applications of ibuprofen derivative in pathologies of the central nervous system (CNS), opening the horizon for new studies. Communicated by Ramaswamy H. Sarma.

Ultrafast optical-domain spectroscopies allow to monitor in real time the motion of nuclei in molecules. Achieving element-selectivity had to await the advent of time resolved X-ray spectroscopy, which is now commonly carried at X-ray free electron lasers. However, detecting light element that are commonly encountered in organic molecules, remained elusive due to the need to work under vacuum. Here, we present an impulsive stimulated Raman scattering (ISRS) pump/carbon K-edge absorption probe investigation, which allowed observation of the low-frequency vibrational modes involving specific selected carbon atoms in the Ibuprofen RS dimer. Remarkably, by controlling the probe light polarization we can preferentially access the enantiomer of the dimer to which the carbon atoms belong.

N-acetyl-β-D-Glucosaminidase (NAGase) is important for crustaceans as the enzyme activity is necessary for the moulting process. The present study aimed to assess the sensitivity of the Palaemon serratus NAGase activity to a set of compounds of diverse chemical families, in a context of in vitro exposures. Compounds representing different chemical families were selected according to their abundance, impact in the environment, and their relevance as disruptors of the moulting process. In a first step, four solvents (DMSO, methanol, acetone, and ethanol) were tested to determine their suitability to dissolve hydrophobic compounds without affecting NAGase activity. Exclusively ethanol had no effect on enzyme activity and on the integrity of proteins present in the enzyme extract. Then, 18 other compounds were tested and six compounds, namely, pentoxifylline, fenoxycarb, dithiocarbamate, and RH5849 showed a specific alteration on the activity of NAGase, without affecting the protein content. However, cadmium, zinc, and glyphosate showed a nonspecific alteration, affecting both the enzyme activity and the proteins, whereas ibuprofen exclusively altered the protein content. Finally, ten of the 22 tested compounds (i.e. including DMSO, acetone and methanol) showed a direct alteration of NAGase activity. This article is protected by copyright. All rights reserved. Environ Toxicol Chem 2023;00:0-0. © 2023 SETAC.