Search Results (174)

Backgroun/Objectives: Recent pharmaceutical research has increasingly focused on eutectic systems to improve the formulation and delivery of active pharmaceutical ingredients (APIs). This study presents the preparation and characterization of three therapeutic eutectic systems (THEESs) based on ibuprofen and menthol at various molar ratios. Methods: The THEESs were prepared and analyzed by assessing their physicochemical properties and rheological properties were evaluated to determine flow behavior. Cytotoxicity assays were conducted on HaCaT and HepG2 cell lines to assess biocompatibility. Results: All systems formed monophasic, homogeneous, clear and viscous liquids. Key physicochemical properties, including density, refractive index, surface tension, speed of sound and isobaric heat capacity, showed a temperature-dependent, inverse proportional trend. Viscosity followed the Vogel–Fulcher–Tammann equation, and rheological analysis revealed non-Newtonian behavior, which is important for pharmaceutical processing. Notably, cytotoxicity assays revealed that Ibu-M3 and Ibu-M4 showed lower toxicity than pure compounds in HaCaT cells, while Ibu-M5 was more toxic; in HepG2 cells, only Ibu-M3 was less toxic, whereas Ibu-M4 and Ibu-M5 were more cytotoxic than the pure compounds. Conclusions: These findings highlight the potential of ibuprofen–menthol eutectic systems for safer and more effective pharmaceutical formulations. Full article

Background: Ibuprofen is one of the most accessible non-steroidal anti-inflammatory drugs (NSADs), exhibiting non-selective reversible inhibition on COX-1 and COX-2. A series of common adverse reactions have been mentioned through the years: gastrointestinal (gastritis, ulceration, hemorrhage, or perforation), renal, hematologic, and cardiovascular. Objective: The aim of this study was to assess the real-world impact of ibuprofen regarding cardiovascular safety, utilizing an established pharmacovigilance database. Methods: Descriptive and disproportionality-based methods were used. Forty specific descriptors of cardiovascular effects were selected. Eight other NSADs and the combination of ibuprofen and pseudoephedrine were used as comparators. Results: A total of 58,760 cases were identified as being associated with ibuprofen in EudraVigilance. Stroke was reported for ibuprofen with a lower probability compared with etoricoxib (ROR: 0.34; 95% CI: 0.21–0.55), celecoxib (ROR: 0.07; 95% CI: 0.06–0.10), meloxicam (ROR: 0.25; 95% CI: 0.14–0.43), acetylsalicylic acid (ROR: 0.07; 95% CI: 0.05–0.09), and ibuprofen/pseudoephedrine (ROR: 0.11; 95% CI: 0.05–0.25). Thrombosis was reported for ibuprofen with a higher probability only relative to ketoprofen (ROR: 2.95; 95% CI: 1.71–5.09). Hypertension was reported for ibuprofen as being more probable than for acetylsalicylic acid (ROR: 1.58; 95% CI: 1.43–1.76). Myocardial infarction was reported as being more probable for ibuprofen than ketoprofen (ROR: 2.31; 95% CI: 1.57–3.40) or nimesulide (ROR: 2.43; 95% CI: 1.25–4.73). Conclusions: Overall, according to our study, the probability of reported cardiovascular adverse reactions is lower than those determined for the rest of the NSAIDs; however, taking into consideration the inherent limitations of the study, further clinical investigations would contribute to a better understanding of the cardiovascular safety of ibuprofen. Full article

The work aimed to investigate the presence of pharmaceutical compounds from the anti-inflammatory class in seawater from the Romanian Black Sea coast and to assess the ecological risk of these substances on the most sensitive organisms. Using the solid-phase extraction technique (SPE) followed by liquid chromatography separation and mass spectrometry detection (LC-MS/MS) of the compounds, the concentrations of these contaminants in selected seawater samples were determined. Ibuprofen was the most commonly detected compound with a frequency of 42.9%, followed by ketoprofen at 31.0.%, diclofenac at 23.8%, and naproxen at 21.4%. The maximum concentrations of pharmaceutical products varied between 13.4 ng/L ketoprofen and 13,575 ng/L caffeine. The order of decreasing maximum concentrations of pharmaceutical compounds in the water of the Black Sea was CAF > IBU > NAP > DIC > KET. The dominant and ubiquitous compound that was determined with the maximum concentration values was caffeine. Strong correlations were observed between three compounds (naproxen: diclofenac, diclofenac: ketoprofen) suggesting the same pollution source. Through the ecological risk assessment, it was observed that both caffeine and ibuprofen can generate high ecological risks for some echinoderms, crustaceans, and fish. Full article

Antenatal inflammation/infection is a major cause of neonatal apnoea and hypoventilation. Prostaglandin E2 (PGE₂) is a key inflammatory mediator associated with depression of fetal and neonatal breathing. We aimed to determine whether antenatal ibuprofen, a cyclooxygenase inhibitor that reduces synthesis of PGE₂, restores fetal breathing movements (FBM) in late-gestation fetal sheep exposed to systemic lipopolysaccharide (LPS). Fetal sheep (125 days gestation, d; term ~148 d) were instrumentally monitored for continuous measurement of FBM and physiological parameters. At 130 d fetuses were randomly allocated between groups receiving i.v. saline (CTL_SAL, n = 9), escalating doses of LPS (i.v.) over 3 days (LPS_SAL, n = 8), or ibuprofen one hour after each LPS dose (LPS_IBU, n = 8). Regular plasma samples were collected for PGE₂ assessment. At 135 d, cerebrospinal fluid and brainstem tissue were collected at autopsy for assessments of PGE₂ expression, and immunohistochemical quantification of astrocytes and microglia within key brainstem respiratory centres was performed to assess inflammation. LPS exposure increased PGE₂ levels in plasma, cerebrospinal fluid and the RTN/pFRG (p < 0.05) and decreased the incidence, amplitude and amount of the accentuated (>5 mmHg) FBMs. Ibuprofen reduced plasma and RTN/pFRG PGE₂ expression (p < 0.01 and p = 0.031, respectively) but did not restore FBMs. Astrocyte and microglial density increased in the RTN/pFRG, NTS and raphe nucleus in LPS_IBU fetuses, compared to LPS_SAL (p < 0.05). Antenatal ibuprofen treatment did not restore depressed FBM, despite reducing the circulating and brainstem PGE₂ levels in LPS-exposed fetal sheep. Other inflammatory pathways or more specific targeting of PGE₂ may be more effective in preventing apnoea caused by exposure to intrauterine infection/inflammation. Full article

A simple, fast, and low-cost pre-concentration methodology based on the application of multi-template molecularly imprinted polymers (mt-MIP) in a solid-phase extraction system coupled with capillary electrophoresis was developed for the determination of naproxen, diclofenac, and ibuprofen in environmental water samples. A systematic study of the mt-MIP composition was conducted using a second-order simplex lattice experiment design (fraction of the functional monomer methacrylic acid (MAA), the total moles of functional monomers, and the total moles of the cross-linker agent). The optimal mt-MIP, consisting of 0.025 mmol of each analyte, with 2.40 mmol of methacrylic acid (MAA) and 3.60 mmol of 4-vinylpyridine (4VP) and 23.00 mmol of the cross-linker agent (EGDMA), was coupled to an SPE system under the optimal conditions: pH = 3.5; 20 mg of mt-MIP; and an eluent (MeOH/NaOH [0.001]). This methodology provides limits of detection from 3.00 to 12.00 µg L⁻¹ for the studied NSAIDs. The methodology’s precision was evaluated in terms of inter- and intra-day repeatability, with %RSD < 10% in all cases. Finally, the proposed method can be successfully applied in the analysis of environmental water samples (bottle, tap, cistern, well, and river water samples), which demonstrates the developed method’s robustness. Full article

Cyclodextrins (CDs) enhance the solubility of poorly water-soluble drugs like ibuprofen (IBU), making them promising carriers for pulmonary drug delivery. This route lowers the required dose, minimizing side effects, which could be beneficial in treating cystic fibrosis. In this study, a nano-spray-drying technique was applied to prepare CD/IBU complexes using sulfobutylether-β-cyclodextrin (SBECD) or (2-Hydroxy-3-N,N,N-trimethylamino)propyl-beta-cyclodextrin chloride (QABCD) as carriers as well as mannitol (MAN) and leucine (LEU) as aerosolization excipients. Various investigation techniques were utilized to examine and characterize the samples, including a Master Sizer particle size analyzer, scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FT-IR). We applied in vitro Andersen Cascade Impactor measurements and in silico simulation analysis to determine the sample’s aerodynamic properties. We also performed in vitro dissolution and diffusion tests. Applying formulations with optimal aerodynamic properties, we achieved an improved ~50% fine particle fraction values based on the Andersen Cascade Impactor measurements. The in vitro dissolution and diffusion studies revealed rapid IBU release from the formulations; however, the QABCD-based sample exhibited reduced membrane diffusion compared to SBECD due to the formation of electrostatic interactions. Full article

In recent years, the incidence of acute and chronic inflammatory diseases has increased significantly worldwide, intensifying the search for new therapeutic agents, especially anti-inflammatory drugs. Therefore, the aim of this work was to synthesize, biologically assess, and explore the structure–activity relationships of new compounds containing the cyclohex-1-ene-1-carboxylic acid moiety. Six new derivatives, 2a–2f, were synthesized through the reaction of amidrazones 1a–1f with 3,4,5,6-tetrahydrophthalic anhydride. Their toxicity was evaluated in cultures of human peripheral blood mononuclear cells (PBMCs). Additionally, their antiproliferative properties and effects on the synthesis of TNF-α, IL-6, IL-10, and IL-1β were assessed in mitogen-stimulated PBMCs. The antimicrobial activity of derivatives 2a–2f was determined by measuring the minimal inhibitory concentration (MIC) values against five bacterial strains—Staphylococcus aureus, Mycobacterium smegmatis, Escherichia coli, Yersinia enterocolitica, and Klebsiella pneumoniae—and the fungal strain Candida albicans. All compounds demonstrated antiproliferative activity, with derivatives 2a, 2d, and 2f at a concentration of 100 µg/mL being more effective than ibuprofen. Compound 2f strongly inhibited the secretion of TNF-α by approximately 66–81% at all studied doses (10, 50, and 100 µg/mL). Derivative 2b significantly reduced the release of cytokines, including TNF-α, IL-6, and IL-10, at a high dose (by approximately 92–99%). Compound 2c exhibited bacteriostatic activity against S. aureus and M. smegmatis, while derivative 2b selectively inhibited the growth of Y. enterocolitica (MIC = 64 µg/mL). Some structure–activity relationships were established for the studied compounds. Full article

Gallic acid (GA) is known for its antioxidant and anti-inflammatory properties, yet its clinical potential is hindered due to poor oral bioavailability. This study investigates novel GA sulfonamide derivatives, 3,4,5-trimethoxybenzenesulfonamide (3,4,5-TMBS) and 3,4,5-trihydroxybenzenesulfonamide (3,4,5-THBS), and determines their antioxidant and anti-inflammatory activities and bioavailability. Antioxidant activity was evaluated using DPPH, FRAP, and ROS assays in human intestinal epithelial cells (HIEC-6). Protein denaturation and COX-2 inhibition were assayed to measure anti-inflammatory effects. 3,4,5-TMBS metabolism was assessed via CYP2D6, and pharmacokinetics were profiled in Sprague Dawley rats. GA and 3,4,5-THBS showed a three-fold increase in ROS scavenging activity at 1000 µM (96% for GA, 93% for 3,4,5-THBS). 3,4,5-TMBS and 3,4,5-THBS demonstrated significant anti-inflammatory activity when compared to ibuprofen at concentrations ≥100 nM (p < 0.05). 3,4,5-TMBS (50 µM) exhibited high COX-2 inhibition (p < 0.001) unlike GA (50 µM) which had a low COX-2 inhibition effect (p > 0.05), compared to ibuprofen. The percentage of 3,4,5-TMBS metabolism increased from 65% to 81% at 1500 µM (p < 0.05) when metabolized by CYP2D6. Pharmacokinetic studies revealed that 3,4,5-TMBS and 3,4,5-THBS had significantly higher C_max and longer half-lives than GA, with 3,4,5-TMBS showing a half-life of 7.17 ± 1.62 h, compared to 3.60 ± 0.94 h for GA (p < 0.05). 3,4,5-TMBS and 3,4,5-THBS demonstrated superior antioxidant and anti-inflammatory effects in HIEC-6 compared to GA, with enhanced bioavailability. These findings support the potential of 3,4,5-TMBS and 3,4,5-THBS as effective alternatives to GA for clinical applications. Full article

Background/Objectives: A common reason for a pediatrician’s visit is acute tonsillopharyngitis (ATR), which is usually caused by viruses. A dietary supplement comprising Pelargonium sidoides extract, honey, propolis, and zinc was proposed as an effective adjuvant for the management of respiratory tract infections. The study aimed to determine the efficacy of this dietary supplement in conjunction with standard of care (SoC) compared to SoC alone, in a pediatric population affected by ATR. Methods: This open randomized study (registered on ClinicalTrials.gov: NCT 04899401) involved three Romanian sites specialized in pediatric care. The primary endpoints were changes in Tonsillitis Severity Score and the number of patients failing to respond (evaluating the use of ibuprofen or high-dose paracetamol as a rescue medication). One hundred and thirty children, distributed into two groups, were enrolled and treated for six days. Results: The results showed an overall better performance in terms of efficacy of dietary supplement + SoC, compared to SoC alone, with lower total Tonsillitis Severity Score ratings on day 6 (p = 0.002) and lower sub-scores related to erythema and throat pain on day 6. No adverse events were reported. Investigators found compliance to be optimal. Conclusions: The administration of the dietary supplement + SoC in pediatric patients with ATR was found to be safe and superior to the administration of SoC alone in terms of efficacy. The results confirmed that the tested dietary supplement is an optimum effective adjuvant in the treatment of respiratory tract infections and is suitable for the daily clinical practice of pediatricians. Full article

Background/Objectives: Oral administration of active pharmaceutical ingredients (APIs) is the most commonly used route of administration. As dysphagia is a prevalent problem, the size of the swallowed dosage form could negatively influence patient adherence. Orally disintegrating tablets (ODTs) are beneficial dosage forms because they disintegrate within a few seconds in the oral cavity without water. Lactose is one of the most commonly used excipients in the pharmaceutical industry; it served as the central concept of a recent publication on the formulation of milk-based ODTs despite lactose malabsorption being widespread worldwide. Consequently, the plant-based alternative market has grown exponentially and has become a prevailing food trend, with various alternatives to choose from. For this reason, the development of a nonsteroidal anti-inflammatory drug (NSAID)-containing ODT with plant-based drinks (PBDs) was assessed for its innovative potential. Methods: Different PBDs were investigated and compared to traditional and lactose-free milk. The liquids’ viscosity, pH, and particle size were determined, and an electronic tongue was used for the sensory evaluation. The various ODTs were prepared with the freeze-drying method, and then the qualitative characteristics of the dosage form were investigated. Results: Our different measurements show that different plant beverages differ from each other and that these differences have an impact on the technological processing. According to the HPLC-DAD measurements, all values were in the required range. Conclusions: These measurements suggest that the soya drink is the most similar to traditional cow milk and would be the most appropriate choice among the investigated plant-based drinks to be used as a carrier system for an ibuprofen-containing ODT. Full article

This paper presents the preparation and study of the properties of alginate materials, which were obtained on the basis of sodium alginate, activated carbon, cellulose, and calcium chloride. Alginate–carbon (AlgCa + C) and alginate–cellulose (AlgCa + Cel) composites, as well as pure calcium alginate (AlgCa) for comparative purposes, were obtained. Their textural (nitrogen adsorption/desorption isotherms), morphological (scanning electron microscopy), thermal (thermal analysis), and acid–base (pH drift method) properties, as well as the swelling index, were investigated. Additionally, to determine the adsorption properties, comprehensive equilibrium and kinetic studies of the adsorption of sodium salts of ibuprofen (IBP), diclofenac (D), and naproxen (NPX) from aqueous solutions on biocomposities were carried out. Adsorption isotherms were fitted using the Marczewski–Jaroniec isotherm equation (R² = 0.941–0.988). Data on the adsorption rate were analyzed using simple kinetic equations, of which the best quality of fit was obtained using the multi-exponential equation (R² − 1 = (3.9 × 10⁻⁴)–(6.9 × 10⁻⁴)). The highest obtained adsorption values were reached in systems with alginate–carbon composite and were 1.23 mmol/g for NPX, 0.81 mmol/g for D, and 0.43 mmol/g for IBP. The AlgCa + C material was characterized by a large specific surface area (1151 m²/g), a high degree of swelling (300%) and high resistance to high temperatures. Full article

A simple method has been developed for the simultaneous analysis of ibuprofen (acid drug), and salbutamol and atenolol (basic drugs) in urine samples at concentrations of 0.40 µg·mL⁻¹. Simultaneous chromatographic separation has been possible using hydrophilic interaction liquid chromatography (Kinetex HILIC^® column (2.1 mm × 150 mm, 2.6 μm particle size diameter and 100 Å pore size) combined with gradient elution by employing a mixture of acetonitrile–acetate buffer 5 mM at pH 6 (from 95:5 to 75:25 (v/v)) as the mobile phase. Detection was performed at 227 and 275 nm. The simultaneous preconcentration and cleaning of the sample has been possible by solid-phase extraction using the HLB ExtraBond^® polymeric-type sorbent (which is a pyrrolidone-modified divinylbenzene polystyrene type). It has provided recoveries between (63 ± 9)% for salbutamol, (74 ± 8)% for ibuprofen, and (96 ± 9)% for atenolol in 10 mL of synthetic urine containing 4.0 μg of each of the drugs analyzed. The detection limits were 0.025 µg·mL⁻¹ for ibuprofen, µg·mL⁻¹ for salbutamol, and 0.007 µg·mL⁻¹ for atenolol. The detection limits obtained allow the evaluation of the free forms of ibuprofen, atenolol, and salbutamol at the excreted concentration levels at the therapeutic doses usually administered. The coefficients of variation between days were in the range 4.5–10.9%. Full article

This study is a preliminary assessment of the emerging and persistent contaminants (EPCs) in the ecologically sensitive Kamphuan Stream in Southern Thailand. The analysis of 15 compounds revealed that EPC concentrations below the main community were significantly elevated during the rainy season, with the highest levels found for sucralose (9070 ng/L), metformin (6250 ng/L), fexofenadine (5110 ng/L), and gabapentin (3060 ng/L). These spatiotemporal patterns highlight the episodic nature of contamination driven by urban stormwater runoff, where rainfall events create temporary pathways that transport EPCs to streams draining into coastal ecosystems. Maximum concentrations of three pharmaceuticals (diclofenac, gemfibrozil, and ibuprofen), as well as sucralose, caffeine, and fenobucarb, exceeded the general predicted no-effect concentrations (PNECs) for marine or fresh waters; however, these concentrations were not persistent. Limited sampling across three campaigns constrained the ability to fully characterize the dynamics of this issue through statistical inference. Furthermore, risk assessments were constrained by the absence of locally derived PNECs for tropical ecosystems and organisms, along with limited standardization in PNEC determination methodologies, making definitive conclusions challenging. A comparative analysis of five priority compounds (diclofenac, gemfibrozil, metformin, naproxen, and fluoxetine) against existing data from East and Southeast Asia underscores the need for further research in Southeast Asia to evaluate the ecological risks posed by EPCs across diverse rivers and streams. Future studies should focus on the contaminants of greatest ecological importance, investigate their transformation products, identify sources and transport pathways, and assess their environmental risks to aquatic ecosystems. Full article

Herein, we report the synthesis of a series of new compounds by combining 2-aminobenzothiazole with various profens. The compounds were characterized using techniques such as ¹H- and ¹³C-NMR, FT-IR spectrometry, and high-resolution mass spectrometry (HRMS), with detailed HRMS analysis conducted for each molecule. Their biological activities were tested in vitro, revealing significant anti-inflammatory and antioxidant effects, comparable to those of standard reference compounds. Lipophilicity was experimentally determined through partition coefficient (R_M) measurements. To understand their binding affinity, molecular docking studies were perfsormed to analyze interactions with human serum albumin (HSA). The stability of these predicted complexes was further evaluated through molecular dynamics simulations. The results highlight the compounds’ promising biological activity and strong affinity for HSA. The new hybrid molecule between 2-ABT and ketoprofen 3b demonstrates significant promise based on the experimental data and is further supported by in silico calculations. Compound 3b exhibits the best hydrogen peroxide scavenging activity among the tested compounds, with an IC₅₀ of 60.24 μg/mL. Furthermore, 3b also displays superior anti-inflammatory activity, with an IC₅₀ of 54.64 μg/mL, making it more effective than the standard ibuprofen (76.05 μg/mL). Full article

The presented study investigated the possibility of using the Acinetobacter johnsonii MC5 strain, isolated from raw sewage by the enrichment culture method, in the bioremediation of soil contaminated with selected NSAIDs, i.e., ibuprofen (IBF), diclofenac (DCF), and naproxen (NPX), using the bioaugmentation technique. The degradation potential of A. johnsonii MC5 was first evaluated using a mineral salt medium containing drugs as the only sources of carbon and energy. The results show that the strain MC5 was capable of utilizing the tested compounds in medium, indicating that the drugs might be metabolically degraded. IBF and NPX were degraded with a similar rate and DT50 values were determined to be approximately 5 days, while the degradation process for DCF was slower, and the DT50 value was about 5 times higher (22.7 days) compared to those calculated for IBF and NPX. Bioaugmentation of non-sterile soil with A. johnsonii MC5 increased the rate of disappearance of the tested drugs, and DT50 values decreased 5.4-, 3.6-, or 6.5-fold for IBF, DCF, or NPX, respectively, in comparison with the values obtained for the soil with indigenous microorganisms only. The obtained results suggest that A. johnsonii MC5 may have potential for use in bioremediation of NSAID-contaminated soils; however, detailed studies are needed before using this strain in such process on a larger scale. Full article