The extensive use of solvents in pharmaceutical manufacturing has major impacts on overall process performance and final product quality. Solvent selection often requires tedious and resource-intensive experimental investigations. Nevertheless, the growing interest in embedding sustainable practices in process development workflows has motivated pharmaceutical manufacturers and researchers to deploy digital tools for enhancing process understanding and guiding the design of greener materials and processes. In this work, a computer-aided mixture/blend design (CAM [b] D) methodology is developed to identify simultaneously the optimal solvent or solvent/antisolvent mixtures, mixture compositions, and process conditions in end-to-end processes, considering integrated synthesis, crystallization, and isolation. Within the proposed approach, thermodynamic models are used to couple property prediction with process modeling to describe pharmaceutical process systems, while mathematical optimization techniques are applied to search the large design space of potential solvents and process conditions and identify the most promising designs among thousands of possible options. Further consideration is also given to the integrated design of reaction, crystallization, and wash solvents, where design decisions across the entire process are interlinked. The methodology is applied to the synthesis, crystallization, and isolation of mefenamic acid as a case study, while considering a broad range of process-wide key performance indicators (KPIs) that quantify product quality and resource efficiency, such as product purity and process energy consumption. In order to explore the trade-offs between competing KPIs, the proposed approach is extended to solve multiobjective design problems and generate a list of Pareto-optimal designs. The results highlight that the optimal designs are strongly dependent on the criteria considered and motivate the need for an integrated approach to solvent selection and process design. The findings of this study are expected to contribute to the digitalization of solvent selection for the accelerated development of sustainable pharmaceutical processes.

Nonsteroidal anti-inflammatory drugs (NSAIDs) possess severe side effects, including various types of gastrointestinal symptoms. Mefenamic acid is one of the most widely used NSAIDs globally. Using an anaerobic in vitro fermentation model, we showed that mefenamic acid reduced the abundance of gut commensals and increased the abundance of pathobionts. Specifically, butyrate-producing commensals were reduced with mefenamic acid treatment. These results corroborate the metabolomics data showing depletion of butyrate, propionate, and their derivatives. Therefore, NSAID consumption could lead to gut dysbiosis, which in turn could lead to gastrointestinal complications generally associated with long-term NSAID use.

Pharmaceutical residues in aquatic environments require reusable sorbents capable of removing structurally diverse contaminants under competitive conditions. Here, a hydrophobic natural deep eutectic solvent-coated silica composite (DES-SOT) was prepared by functionalizing silica gel with n-octyltriethoxysilane followed by immobilization of a thymol:oleic acid deep eutectic solvent. Characterization confirmed formation of a DES-rich organic interfacial layer. DES-SOT showed higher adsorption capacities than unmodified silica and Si-OTES for diclofenac, ibuprofen, mefenamic acid, and tolfenamic acid, with equilibrium reached within 20 min at pH 6. Kinetic and isotherm analyses described heterogeneous adsorption behavior, while reusability, desorption, and molecular dynamics results were consistent with hydrophobic partitioning and weak noncovalent interactions. Molecular dynamics simulations supported analyte-dependent association with the DES-rich interface, consistent with experimental adsorption trends. DES-SOT maintained adsorption performance in groundwater and lake water and remained reusable over five adsorption-desorption cycles. This study demonstrates a simple DES-based adsorption interface for pharmaceutical removal from water.

The interaction between carbon dioxide and molecularly confined pharmaceutical compounds can result in CO2 retention that exceeds that achieved through conventional physical adsorption. This study investigates CO2 retention following sorption in hydrophilic and hydrophobic silica aerogels containing the fenamates mefenamic acid and flufenamic acid. The Thermal stability of the retained CO2 was characterized using temperature-programmed oxidation and temperature-programmed desorption measurements. Concurrently, single-point nitrogen adsorption measurements monitored relative changes in the apparent accessible surface area of the porous matrix. Untreated silica aerogels did not exhibit a significant CO2 desorption peak at elevated temperatures. In contrast, all composites containing fenamates exhibited an additional high-temperature desorption step beginning at approximately 225 °C, indicating enhanced CO2 retention after sorption once the external CO2 layer was removed. This characteristic persisted following preliminary thermal treatment, suggesting it is not solely attributable to residual volatile substances. Surface-area measurements indicated minimal changes in the original aerogels after the CO2 cycle, whereas composites with flufenamic acid demonstrated more pronounced alterations. Considering previous nuclear magnetic resonance, spectroscopic, and computational studies, these findings suggest a combined effect of nanoconfinement, surface-dependent interfacial phenomena, and specific interactions involving the fenamate-containing phase. Reversible chemical interactions may contribute to the observed retention, although the current measurements do not allow for quantitative separation of their effects from those of physical confinement.

Recent studies demonstrated that serotonergic system, specially 5-HT3 receptor (5-HT3R) plays major role in regulating mood and anxiety. The present study investigates antidepressant- and anxiolytic-like effects of a 5-HT3 receptor antagonist (5-HT3RA), (2-((2,3-dimethylphenyl)amino)phenyl)(4- ethylpiperazin-1-yl)methone) (MP-02), in mouse model of corticosterone-induced depression. Chronic administration of corticosterone (CORT) was done to induce depression- and anxiety-like behaviour in mice. It mimics stress-related pathophysiology due to involvement of HPA axis. Behavioural evaluations, such as spontaneous locomotor activity (SLA), forced swim test (FST), tail suspension test (TST), open field test (OFT), elevated plus maze (EPM), light and dark (L&D) test, sucrose preference test (SPT), were performed to assess antidepressant-and anxiolytic-like effects. Biochemical evaluations such as plasma CORT and serotonin, brain inflammatory marker and oxidative stress marker levels were measured in mouse brain. Administration of MP-02 led to significant reduction in immobility time during the FST and TST and increased % sucrose preference in SPT, which reflects antidepressant-like effect and it enhances the exploratory behaviour in OFT, EPM and L&D test which indicates anxiolytic-like effects. It also decreases the levels of plasma CORT and brain inflammatory markers TNF-α, IL-1β and oxidative stress marker, MDA and increases the levels of brain serotonin and anti-oxidant enzyme catalase and SOD. However, MP-02 was not affected the levels of BDNF in mouse brain. The present study demonstrated the potential antidepressant and anxiolytic-like effects of MP-02 in mice. The results were further supported by docking simulations, offering molecular insights into the understanding of the experimental results.

A mesoporous silica-encapsulated wheat straw-derived carbon dots functionalized with Schiff base silane pockets (m-SiO2_ws-CDs@SBs) has been developed. m-SiO2_ws-CDs@SBs provides a synergistic platform that integrates the benefits of each component, including the optical properties of CDs, the high surface area and robustness of m-SiO2, and the molecular recognition capabilities of Schiff bases. The fluorescence of m-SiO2_ws-CDs@SBs remained constant, whereas upon the addition of aspirin (ASP), the fluorescence of m-SiO2_ws-CDs@SBs was quenched. m-SiO2_ws-CDs@SBs exhibit high sensitivity (limit of detection = 3.69 nM), linearity over a concentration range between 18-140 nM with R [2] of 0.9809. The m-SiO2_ws-CDs@SBs showed pronounced fluorescence quenching towards ASP and excellent selectivity for ASP in the presence of other pharmaceutical drugs, i.e., diclofenac, ibuprofen, naproxen, and mefenamic acid. Moreover, it displayed negligible interference from common excipients and metal ions at 1 : 1 and 1 : 10 molar ratios of ASP and interferent, respectively. The fluorescent probe has been used to analyze ASP in an aspirin drug product available at a local pharmacy, as well as in tap water and river water with an excellent recovery of 95.00-99.44%.

Schistosomiasis is an acute and chronic illness caused by parasites of the genus Schistosoma. It is present in 79 countries worldwide and primarily affects socioeconomically vulnerable populations due to exposure to infested water during daily activities. Praziquantel is the primary drug used in international schistosomiasis treatment. However, adverse effects and parasite resistance mechanisms have been reported, ranging from experimentally induced resistance to naturally occurring resistance in real-world populations. New therapeutic targets have been identified to address these issues. Consequently, drug repurposing is often considered a faster alternative that may offer lower development risks and potentially fewer adverse outcomes than newly synthesized drugs. Building on this potential, this study aimed to identify drug repurposing candidates as alternatives for schistosomiasis treatment through a systematic review. Two databases (ScienceDirect and PubMed) were searched. The selection of studies and writing of this systematic review followed the PRISMA guidelines. Of the 313 articles identified, 28 were selected after applying the exclusion criteria. The best results observed were celecoxib (over 90% for egg burden and parasite load), mefenamic acid (92% for parasite load and 82% for egg burden), and chlorambucil (75% parasite load and 85% egg burden). This review highlights the data supporting this strategy as a viable alternative for developing new therapies for schistosomiasis. As these compounds have been used clinically for a long time, substantial preclinical, biosafety, and pharmacovigilance data are already available. Their adverse effects and toxicities are well characterized, which may contribute to a reduction in overall costs and development timelines, although robust clinical validation remains a prerequisite for their use.

Sepsis survivors frequently develop long-term cognitive impairment, but the mechanisms linking systemic infection to persistent brain dysfunction remain incompletely understood. Mitochondrial dysfunction and NLRP3 inflammasome activation have been implicated in sepsis-associated encephalopathy and may represent therapeutic targets. Here, we investigated whether chronic treatment with mefenamic acid (MFA), a fenamate with reported anti-inflammatory and neuroprotective properties, attenuates late neuroinflammatory, mitochondrial, and cognitive alterations in a rat model of cecal ligation and puncture. Sepsis induced persistent NLRP3 inflammasome activation, increased IL-1β and IL-18 levels, microglial reactivity, mitochondrial ROS production, mtDNA 8-oxoG accumulation, oxidative damage, impaired respiratory chain activity, and long-term spatial and aversive memory deficits. MFA treatment, particularly at 30 and 50 mg/kg, reduced inflammasome-associated inflammatory responses and mitochondrial oxidative injury, preserved respiratory chain complex activities, modulated markers of mitophagy and mitochondrial biogenesis, and improved cognitive performance. MFA also reduced amyloid-β accumulation and increased transthyretin levels, suggesting modulation of neurodegeneration-related pathways after sepsis. These findings are consistent with a protective effect of MFA against sepsis-associated long-term brain dysfunction and identify NLRP3-associated neuroinflammation and mitochondrial damage as interconnected pathways for further therapeutic investigation.

The bromodomain and extra-terminal (BET) family of proteins, which regulate chromatin function, is an established potential drug target for treating major diseases such as cancer and inflammatory conditions. There is significant research focused on developing new BET inhibitors with innovative molecular structures to target and modulate the epigenetic mechanisms underlying major diseases, including cancer. Herein, we present the crystal structures of the second bromodomain (BD2) of hBRD2 in complex with the FDA-approved drugs, mefenamic acid (ID8) and nimesulide (NIM), and that of the first bromodomain (BD1) of hBRD4 in complex with nimesulide (NIM). Quantitative binding assays by surface plasmon resonance (SPR) confirmed the substantial binding of these drug molecules to the hBRD2 and hBRD4 bromodomains. Using these crystal structures, a series of ID8 and NIM derivatives with improved affinity relative to the parent compounds was designed and evaluated using SeeSAR (BioSolveIT GmbH). Moreover, molecular dynamics simulations were performed on the selected derivatives of ID8 and NIM against these bromodomains and confirmed the stability of these derivatives' binding throughout the simulations. We propose that the derivatives of the aforementioned parent molecules may be potential inhibitors of the function of hBRD2 and hBRD4.

The role of two different non-steroidal anti-inflammatory drugs, namely, mefenamic acid (MA) (2-[(2,3-dimethylphenyl)amino]benzoic acid) and aceclofenac (ACF) (2-[(2,6-dichlorophenyl)amino]phenyl acetoxyacetic acid), and their electrostatic interactions with bovine serum albumin (BSA) and adenine model systems have been studied. The binding affinity for drug formation depends primarily on the heterocyclic ring and functional groups. The hydrophobic interactions were also evaluated. The spectral properties of the interactions were investigated by UV-visible, fluorescence, FT-IR, cyclic voltammetry and molecular modelling methods. In addition, the Stern-Volmer plots for BSA and adenine with the drug molecules are shown. Moreover, the static quenching interaction, the binding constant (Ka) and the number of sites (n) have been determined. The binding efficiency is evaluated and compared on the basis of its E value. The free energy, van der Waals and hydrogen-bonding interaction values of BSA with the drugs are determined. In order to assess the electrochemical process, the scan rate is another important parameter, which has been determined by using cyclic voltammograms.

Background: An increasing number of commercially available drug substances and bioactive ingredients are characterized by poor flowability. Inadequate flow properties may lead to material blockage during transport within production lines, as well as the formation of air voids within the bulk. Such phenomena can disrupt the technological process and may even result in batches that fail to meet quality requirements. Therefore, ensuring adequate powder flow is of utmost importance in the manufacture of health-related products. Methods: Binary mixtures were prepared using one of four model substances (ibuprofen, metamizole sodium, mefenamic acid, or sunflower lecithin) combined with a glidant (colloidal silica, precipitated silica, or tricalcium phosphate). The glidant content ranged from 0.5 to 10.0% w/w depending on the model substance, and mixing was carried out for 5-30 min. The resulting binary mixtures were evaluated for flow properties using the angle of repose method, and in selected cases, bulk density was also determined. Results/Conclusions: The study demonstrated that powder flow improvement depended not only on the glidant but primarily on the properties of the host material (particle size, shape, and bulk density). Coarser powders such as ibuprofen responded well to low glidant levels, although excessive silicon dioxide caused oversilication. Metamizole sodium showed progressively better flow with increasing particle size and density, and tribasic calcium phosphate further improved performance, particularly with longer mixing times. Very fine or cohesive powders, such as mefenamic acid and sunflower lecithin, showed limited response to silica-based glidants, whereas tribasic calcium phosphate proved more effective and additionally increased bulk density. Overall, no universal glidant strategy was identified; effective flow enhancement requires a tailored approach based on specific powder characteristics.

A low-cost electrochemical sensor based on a graphite screen-printed carbon electrode modified with nickel nanoparticles was developed for the sensitive determination of mefenamic acid (MFA), an emerging environmental contaminant due to its persistence and incomplete removal in wastewater treatment, which may lead to endocrine-disrupting effects in aquatic systems. The incorporation of nickel nanoparticles into the graphite-based ink significantly increased the electroactive surface area and enhanced electron transfer kinetics, resulting in improved analytical performance. Morphological and structural analyses confirmed the successful integration of nickel nanoparticles into the electrode matrix. Electrochemical characterization using cyclic voltammetry and electrochemical impedance spectroscopy demonstrated higher faradaic currents and lower charge transfer resistance compared to the unmodified electrode. Under optimized conditions, differential pulse voltammetry provided a well-defined oxidation signal for mefenamic acid, with a linear range from 0.5 to 12.20 µmol L[-1], a limit of detection of 69.12 nmol L[-1], and a sensitivity of 0.434 µA L µmol[- 1]. The sensor exhibited good repeatability (RSD = 3.85%), satisfactory long-term stability (88% signal retention after 30 days), and excellent recovery (96-99%) in tap and river water samples. The proposed platform combines sensitivity, reliability, low cost, and operational simplicity, demonstrating strong potential for on-site environmental monitoring of mefenamic acid.