Development of an eco-friendly fluorescent probe for mefenamic acid sensing in pharmaceuticals and biofluids.

Mefenamic acid, renowned for its analgesic properties, stands as a reliable choice for alleviating mild to moderate pain. However, its versatility extends beyond pain relief, with ongoing research unveiling its promising therapeutic potential across diverse domains. A straightforward, environmentally friendly, and sensitive spectrofluorometric technique has been developed for the precise quantification of the analgesic medication, mefenamic acid. This method relies on the immediate reduction of fluorescence emitted by a probe upon interaction with varying concentrations of the drug. The fluorescent probe utilized, N-phenyl-1-naphthylamine (NPNA), was synthesized in a single step, and the fluorescence intensities were measured at 480 nm using synchronous fluorescence spectroscopy with a wavelength difference of 200 nm. Temperature variations and lifetime studies indicated that the quenching process was static. The calibration curve exhibited linearity within the concentration range of 0.50-9.00 µg/mL, with a detection limit of 60.00 ng/mL. Various experimental parameters affecting the quenching process were meticulously examined and optimized. The proposed technique was successfully applied to determine mefenamic acid in pharmaceutical formulations, plasma, and urine, yielding excellent recoveries ranging from 98% to 100.5%. The greenness of the developed method was evaluated using three metrics: the Analytical Eco-scale, AGREE, and the Green Analytical Procedure Index.

New fluorescent probe for sensing of mefenamic acid in aqueous medium: An integrated experimental and theoretical analysis.

Abnormal levels of mefenamic acid (MFA) in living organisms can result in hepatic necrosis, liver, and gastrointestinal diseases. Therefore, development of accurate and effective method for detection of MFA is of great significance for the protection of public health. Herein, we designed a stilbene based sensor ECO for the sensitive and selective detection of mefenamic acid by employing fluorescence spectroscopy for the first time. The developed sensor ECO displayed fluorescence turn-off response towards MFA based on PET (photoinduced electron transfer) and hydrogen bonding. The sensing mechanism of MFA was investigated through 1H NMR titration experiment and density functional theory (DFT) calculations. The presence of non-covalent interaction was confirmed through spectroscopic analysis and was further supported by non-covalent interaction (NCI) analysis and Bader's quantum theory of atoms in molecules (QTAIM) analysis. Additionally, the sensor ECO coated test strips were fabricated for on-site detection of mefenamic acid. Furthermore, the practical applicability of sensor ECO to detect MFA was also explored in human blood and artificial urine samples.

Prediction of Mefenamic Acid Crystal Shape by Random Forest Classification.

OBJECTIVE: Particle shape can have a significant impact on the bulk properties of materials. This study describes the development and application of machine-learning models to predict the crystal shape of mefenamic acid recrystallized from organic solvents. METHODS: Crystals were grown in 30 different solvents to establish a dataset comprising solvent molecular descriptors, process conditions and crystal shape. Random forest classification models were trained on this data and assessed for prediction accuracy. RESULTS: The highest prediction accuracy of crystal shape was 93.5% assessed by fourfold cross-validation. When solvents were sequentially excluded from the training data, 32 out of 84 models predicted the shape of mefenamic acid crystals for the excluded solvent with 100% accuracy and a further 21 models had prediction accuracies from 50-100%. Reducing the feature set to only solvent physical property descriptors and supersaturations resulted in higher overall prediction accuracies than the models trained using all available or another selected subset of molecular descriptors. For the 8 solvents on which the models performed poorly (< 50% accuracy), further characterisation of crystals grown in these solvents resulted in the discovery of a new mefenamic acid solvate whereas all other crystals were the previously known form I. CONCLUSIONS: Random forest classification models using solvent physical property descriptors can reliably predict crystal morphologies for mefenamic acid crystals grown in 20 out of the 28 solvents included in this work. Poor prediction accuracies for the remaining 8 solvents indicate that further factors will be required in the feature set to provide a more generalized predictive morphology model.

Enhanced Mefenamic Acid Release from Poloxamer-Silicon Dioxide Gel Filled in Hard Gelatin Capsules - An Application of Liquid Semisolid Matrix Technology for Insoluble Drug.

INTRODUCTION: Liquid Semisolid Matrix (LSSM) technology involves the filling of drugmixed gel in hard gelatin capsules for different applications. METHODS: In continuation of our previous work on LSSM technology, 10% (w/w) of practically insoluble model drug, mefenamic acid was incorporated in gels of different poloxamers with 8% (w/w) SiO2. RESULTS: Gels exhibited plasticity or pseudoplasticity along thixotropy at 2 and 24 h enabling their easy filling into hard gelatin capsules without content seepage. Mefenamic acid gels prepared with L64 and L92 maintained their apparent viscosities for the study period of one month. Around 100% mefenamic acid was released within 90 min from L64- and in 150 min from L92-SiO2 gels, both with first-order kinetics. In 12 month long-term stability studies, only mefenamic acid-L64- SiO gel at 30°C/65% RH indicated dispersion stability with similar rheology and release pattern to that at 2, 24 and 30 days. No chemical drug-polymer interactions were found in FTIR. CONCLUSION: The release of practically insoluble mefenamic acid could be enhanced from gel formulated with L64 and SiO2.

Construction of a Drug Release Evaluation System: Application of Mitochondrial Respiration to Monitor Drug Release.

BACKGROUND/AIM: Efficient drug encapsulation and regulation of drug release are important factors for sustained drug release and application for release-controlled anti-cancer and anti-inflammatory drug delivery. In the present study, a direct evaluation system for drug-release from model carrier (e.g., alginate-gel beads) was examined using the mitochondrial oxygen consumption rate as an index. MATERIALS AND METHODS: Alginate-gel beads were coated with the uncoupler SF6847 (SF beads) and used as a model microparticle-type drug. The real-time monitoring of SF6847 release from prepared alginate-gel beads was performed using the mitochondrial oxygen consumption rate. Release profiles of nonsteroidal anti-inflammatory drugs [NSAIDs, mefenamic acid (MEF) and diclofenac (DIC)] from alginate-gel beads as well as SF beads were investigated using the real time monitoring system. RESULTS: SF6847 release from alginate-gel beads was clearly detected using the rat liver mitochondrial oxygen consumption rate. The release features of MEF and DIC from alginate-gel beads were defined by the present trial monitoring system, and these NSAIDs exhibited different release profiles. CONCLUSION: The present drug monitoring system detected released drugs, and the release profile reflected the molecular properties of the test drugs. This system may be applied to the design and development of precise sustained drug release systems (e.g., anti-cancer and anti-inflammatory drugs).

Molecular docking-guided synthesis of NSAID-glucosamine bioconjugates and their evaluation as COX-1/COX-2 inhibitors with potentially reduced gastric toxicity.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a powerful class of inhibitors targeting two isoforms of the family of cyclooxygenase enzymes (COX-1 and COX-2). While NSAIDs are widely used in the management of pain, in particular as a treatment for osteo- and rheumatoid arthritis, their long-term use has been associated with numerous on- and off-target effects. As the carboxylic acid moiety present in common NSAIDs is responsible for some of their adverse effects, but is not required for their anti-inflammatory activity, we sought to mask this group through direct coupling to glucosamine, which is thought to prevent cartilage degradation. We report herein the conjugation of commonly prescribed NSAIDs to glucosamine hydrochloride and the use of molecular docking to show that addition of the carbohydrate moiety to the parent NSAID can enhance binding in the active site of COX-2. In a preliminary, in vitro screening assay, the diclofenac-glucosamine bioconjugate exhibited 10-fold greater activity toward COX-2, making it an ideal candidate for future in vivo studies. Furthermore, in an intriguing result, we observed that the mefenamic acid-glucosamine bioconjugate displayed enhanced activity toward COX-1 rather than COX-2.

Solubility enhancement of mefenamic acid by inclusion complex with ß-cyclodextrin: in silico modelling, formulation, characterisation, and in vitro studies.

The aim of this study was to prepare and characterise inclusion complexes of a low water-soluble drug, mefenamic acid (MA), with ß-cyclodextrin (ß-CD). First, the phase solubility diagram of MA in ß-CD was drawn from 0 to 21 × 10-3 M of ß-CD concentration. A job's plot experiment was used to determine the stoichiometry of the MA:ß-CD complex (2:1). The stability of this complex was confirmed by molecular modelling simulation. Three methods, namely solvent co-evaporation (CE), kneading (KN), and physical mixture (PM), were used to prepare the (2:1) MA:ß-CD complexes. All complexes were fully characterised. The drug dissolution tests were established in simulated liquid gastric and the MA water solubility at pH 1.2 from complexes was significantly improved. The mechanism of MA released from the ß-CD complexes was illustrated through a mathematical treatment. Finally, two in vitro experiments confirmed the interest to use a (2:1) MA:ß-CD complex.

The general anesthetic etomidate and fenamate mefenamic acid oppositely affect GABAAR and GlyR: a structural explanation.

GABA and glycine act as inhibitory neurotransmitters in the CNS. Inhibitory neurotransmission is mediated via activation of ionotropic GABAA and glycine receptors. We used a modeling approach to explain the opposite effects of the general anesthetic etomidate (ETM) and fenamate mefenamic acid (MFA) on GABA- and glycine-activated currents recorded in isolated cerebellar Purkinje cells and hippocampal pyramidal neurons, respectively. These drugs potentiated GABAARs but blocked GlyRs. We built a homology model of α1ß GlyR based on the cryo-EM structure of open α1 GlyR, used the α1ß3γ2 GABAAR structure from the PDB, and applied Monte-Carlo energy minimization to optimize models of receptors and ligand-receptor complexes. In silico docking suggests that ETM/MFA bind at the transmembrane ß( +)/α( -) intersubunit interface in GABAAR. Our models predict that the bulky side chain of the highly conserved Arg19' residue at the plus interface side wedges the interface and maintains the conducting receptor state. We hypothesized that MFA/ETM binding at the ß( +)/α( -) interface leads to prolongation of receptor life-time in the open state. Having analyzed different GABAAR and GlyR structures available in the PDB, we found that mutual arrangement of the Arg19' and Gln-26' side chains at the plus and minus interface sides, respectively, plays an important role when the receptor switches from the open to closed state. We show that this process is accompanied by narrowing of the intersubunit interfaces, leading to extrusion of the Arg19' side chain from the interface. Our models allow us to explain the lack of GlyR potentiation in our electrophysiological experiments.

Anticancer Potential of Mefenamic Acid Derivatives with Platelet-Derived Growth Factor Inhibitory Property.

BACKGROUND: Numerous studies suggest that non-steroidal anti-inflammatory drugs reduce cancer cell proliferation, progression, angiogenesis, apoptosis, and invasiveness. OBJECTIVE: The current study focuses on the evaluation of novel mefenamic acid derivatives for the treatment of hepatocellular carcinoma. METHODS: Derivatives were subjected to molecular modeling for prediction of pharmacological activity using software, followed by synthesis and in vitro assay. In in vivo study, disease was induced with N-Nitrosodiethylamine followed by 2-acetylaminofluorene orally for 2 weeks. After 12 weeks of induction, treatment was given for a period of one week. At the end of the treatment, determination of liver weight, a number of nodules, biochemical parameters, immunohistochemistry, histopathology, and gene expression studies, were carried out. RESULTS: Based on molecular docking score for PDGF-α (Platelet-Derived Growth Factor) and IC50 values in HepG2 cell line study, JS-PFA was selected for the in vivo study where JS-PFA showed a statistically significant reduction in a number of nodules and liver weight. Protective role of JS-PFA has been observed in tumorspecific markers like α-fetoprotein, carcinoembryonic antigen, and lactate dehydrogenase levels. The JS-PFA has shown a significant reduction in PDGF-α levels as well as liver markers and total bilirubin levels. Histopathological analysis also showed a protective effect. The results of immunohistochemical analysis of P53 and down-regulation of vascular endothelial growth factor and matrix metalloproteinases-9 genes suggest that derivative inhibits PDGF mediated tumor growth and leads to apoptosis, inhibition of angiogenesis, and metastasis. CONCLUSION: The effectiveness of JS-PFA in our studies suggests targeting PDGF by COX 2 inhibitor can serve as a novel treatment strategy for the treatment of HCC.

Ultrasound assisted rapid synthesis of mefenamic acid based indole derivatives under ligand free Cu-catalysis: Their pharmacological evaluation.

An improved and rapid synthesis of mefenamic acid based indole derivatives has been achieved via the ligand free Cu-catalyzed coupling-cyclization method under ultrasound irradiation. This simple, straightforward and inexpensive one-pot method involved the reaction of a terminal alkyne derived from mefenamic acid with 2-iodosulfanilides in the presence of CuI and K2CO3 in PEG-400. The reaction proceeded via an initial CC bond formation (the coupling step) followed by CN bond formation (the intramolecular cyclization) to afford the mefenamic acid based indole derivatives in good to acceptable yields. Several of these compounds showed inhibition of PDE4 in vitro and the SAR (Structure Activity Relationship) within the series is discussed. The compound 3d has been identified as a promising and selective inhibitor of PDE4B (IC50 = 1.34 ± 0.46 µM) that showed TNF-α inhibition in vitro (IC50 = 5.81 ± 0.24 µM) and acceptable stability in the rat liver microsomes.

Covalent polybenzimidazole-based triazine frameworks: A robust carrier for non-steroidal anti-inflammatory drugs.

Covalent triazine-based polymers (CTPs) are a new class of porous materials that can be used for the intercalation of therapeutic agents. The main purposes of designing new drug carriers include protecting them from degradation, enhancing their poor aqueous solubility, and investigating their controlled release properties. In this context, a novel polybenzimidazole-based CTP (BZ-CTP) was prepared by a solvothermal reaction between 4,4',4″-((1,3,5-triazine-2,4,6-triyl) tris(azanediyl)) tribenzoic acid (TCA) and 3,3'-diaminobenzidine. Piroxicam (PRX) and mefenamic acid (MFA) were loaded thoroughly into the CTP by using ultrasonication to form MFA-loaded CTP (MFA@BZ-CTP) and PRX-loaded CTP (PRX@BZ-CTP) with drug loading efficiencies of 49% and 53%, respectively. We attribute the increased loading efficiencies to the formation of π-π stacking forces between the aromatic rings present in the CTP structure and drugs. The in vitro release experiments were assessed in simulated physiological conditions using the dialysis method. Moreover, the release mechanisms were evaluated by Korsmeyer-Peppas kinetic studies and the obtained results showed excellent sustained releases of 81% after 96 h and 87% after 24 h for the PRX@BZ-CTP and MFA@BZ-CTP hybrids, respectively.

Molecular Docking and In Silico Cogitation Validate Mefenamic Acid Prodrugs as Human Cyclooxygenase-2 Inhibitor.

In silico molecular docking is an efficient technique for drug design that predicts the optimized orientation of the ligand against a specific drug target. This is a cost-effective and time-saving technique that requires limited manpower. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed drugs in various prescriptions. The drawbacks with NSAIDs in its long-term usage are gastric irritation, bleeding, and perforation. Prodrug approach is a commonly used method to overcome these side effects. In this study, the reported prodrugs of mefenamic acid were utilized to validate the molecular docking simulation process by comparing obtained in silico results with the reported in vivo results. The molecules were evaluated for their binding affinity against human cyclooxygenase-2 enzyme as well as their pharmacokinetics profile is predicted on the basis of Lipinski's and Veber rule. The in silico result showed high degree similarity with experimental results. This confirms the efficiency and reliability of the molecular docking technique for identification of potential lead compounds.

Rat palatability, pharmacodynamics effect and bioavailability of mefenamic acid formulations utilizing hot-melt extrusion technology.

Mefenamic acid (MA) has been reported as a weakly soluble drug which presents weak in vivo absorption upon oral administration using conventional formulations. Solid dispersions (SDs) have been investigated extensively in literature for enhancing the solubility and bioavailability of weakly-soluble molecules. Hence, the aim of proposed study was to prepare MA novel formulations in the form of SDs using hot-melt extrusion technology in order to enhance its palatability, bioavailability, and pharmacodynamics effects/anti-inflammatory efficacy. Various SDs of MA were prepared using hot-melt extrusion technology, characterized physically and investigated for dissolution tests. Optimized SD formulations of MA were being subjected to palatability, pharmacodynamics, and pharmacokinetic studies in rats. Optimized SD of MA showed significant rat palatability tastes as compared with pure and marketed MA (p < .05). Anti-inflammatory efficacy of 20% SD and 25% SD of MA was found to be 86.44 and 89.83%, respectively, in comparison with 74.57 and 78.24% by pure MA and marketed MA, respectively. The anti-inflammatory efficacy of optimized SD was found to be significant as compared with pure and marketed MA (p < .05). The oral absorption of MA from optimized 20% SD was also noted as statistically significant as compared with pure MA (p < .05). The relative bioavailability of MA from 20 and 25% SDs was 2.97 and 2.24-folds higher than pure MA. The results of this study suggested that SDs prepared using hot-melt extrusion technology are capable to enhance palatability, anti-inflammatory efficacy, and oral bioavailability of MA in comparison with pure drug.

A novel high-performance liquid chromatographic method combined with fluorescence detection for determination of ertugliflozin in rat plasma: Assessment of pharmacokinetic drug interaction potential of ertugliflozin with mefenamic acid and ketoconazole.

Ertugliflozin (ERTU) is a novel, potent, and highly selective sodium glucose cotransporter 2 inhibitor that has been recently approved for the treatment of type 2 diabetes mellitus. We describe a novel bioanalytical method using high-performance liquid chromatography (HPLC) coupled with fluorescence detection for quantitative determination of ERTU in rat plasma. Acetonitrile-based protein precipitation method was used for sample preparation, and chromatographic separation was performed on a Kinetex® C18 column with an isocratic mobile phase comprising acetonitrile and 10 mM potassium phosphate buffer (pH 6.0). The eluent was monitored by a fluorescence detector at an optimized excitation/emission wavelength pair of 277/320 nm. The method was validated to demonstrate the selectivity, linearity (ranging from 4 to 2000 ng/mL), precision, accuracy, recovery, matrix effect, and stability in line with the current FDA guidelines. The newly developed method was successfully applied to investigate the pharmacokinetic interactions of ERTU with mefenamic acid (MEF) and ketoconazole (KET). The findings of the present study revealed that the pharmacokinetics of ERTU may be altered by concurrent administration of MEF and KET in rats. To our knowledge, the present study is the first to develop a validated bioanalytical method for quantification of ERTU using HPLC coupled with fluorescence detection and to assess the drug interaction potential of ERTU with non-steroidal anti-inflammatory (MEF) and azole antifungal (KET) drugs.

Intercalation of manganese-mefenamic acid complex into double stranded of calf thymus DNA.

The interaction of the [Mn(mef)2(phen)H2O] complex in which mef is mefenamic acid drug and phen is 1,10 phenanthrolin ligand with calf thymus DNA (ct-DNA) was studied by using different spectroscopic methods, molecular docking and viscometery. The competitive fluorescence and UV-Vis absorption spectroscopy indicated that the complex interacted with ctDNA via intercalating binding mode with the binding constant of 1.16 × 104 Lmol-1. The thermodynamic studies showed that the reaction between the complex and ctDNA is exothermic. Furthermore, the complex induced changes in DNA viscosity. Circular dichroism spectroscopy (CD) was employed to measure the conformational changes of ctDNA in the presence of the complex and verified intercalation binding mode. The molecular modeling results illustrated that the complex interacted via intercalation by relative binding energy of -28.45 kJ mol-1.

Methacrylate-Copolymer Eudragit EPO as a Solubility-Enabling Excipient for Anionic Drugs: Investigation of Drug Solubility, Intestinal Permeability, and Their Interplay.

The purpose of this work was to investigate the use of the dimethylaminoethyl methacrylate-copolymer Eudragit EPO (EPO) in oral solubility-enabling formulations for anionic lipophilic drugs, aiming to guide optional formulation design and maximize oral bioavailability. We have studied the solubility, the permeability, and their interplay, using the low-solubility nonsteroidal anti-inflammatory drug mefenamic acid as a model drug. Then, we studied the biorelevant solubility enhancement of mefenamic acid from EPO-based formulations throughout the gastrointestinal tract (GIT), using the pH-dilution dissolution method. EPO allowed a profound and linear solubility increase of mefenamic acid, from 10 µg/mL without EPO to 9.41 mg/mL in the presence of 7.5% EPO (∼940-fold; 37 °C); however, a concomitant decrease of the drug permeability was obtained, both in vitro and in vivo in rats, indicating a solubility-permeability trade-off. In the absence of an excipient, the unstirred water layer (UWL) adjacent to the GI membrane was found to hinder the permeability of the drug, accounting for this UWL effect and revealing that the true membrane permeability allowed good prediction of the solubility-permeability trade-off as a function of EPO level using a direct relationship between the increased solubility afforded by a given EPO level and the consequent decreased permeability. Biorelevant dissolution studies revealed that EPO levels of 0.05 and 0.1% were insufficient to dissolve mefenamic acid dose during the entire dissolution time course, whereas 0.5 and 1% EPO allowed complete solubility with no drug precipitation. In conclusion, EPO may serve as a potent solubility-enabling excipient for BCS class II/IV acidic drugs; however, it should be used carefully. It is prudent to use the minimal EPO amounts just sufficient to dissolve the drug dose throughout the GIT and not more than that. Excess amounts of EPO provide no solubility gain and cause further permeability loss, jeopardizing the overall success of the formulation. This work may help the formulator to hit the optimal solubility-permeability balance, maximizing the oral bioavailability afforded by the formulation.

Cobalt(II) complexes with the non-steroidal anti-inflammatory drug diclofenac and nitrogen-donor ligands.

The interaction of the non-steroidal anti-inflammatory drug sodium diclofenac with CoCl2 in the absence or presence of the nitrogen-donor ligands 2,2'-bipyridine, 1,10-phenanthroline, 2,2'-bipyridylamine, pyridine or imidazole resulted in the formation of six mononuclear Co(II) complexes. The complexes were characterized by diverse physicochemical and spectroscopic techniques and single-crystal X-ray crystallography revealing a monodentate or a bidentate chelating binding mode of the diclofenac ligands. The scavenging activity of the complexes was evaluated in vitro against the free radicals of 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydroxyl; the complexes present significant scavenging activity of ABTS and hydroxyl radicals. The interaction of the complexes with calf-thymus (CT) DNA and bovine serum albumin (BSA) was also investigated; the complexes can bind tightly to CT DNA via intercalation and can bind to BSA tightly and reversibly.

Chemometric study of the excipients' influence on polymorphic-behavior. Mefenamic acid as case of study.

The assessment of polymorphism is a problematical issue for regulatory agencies, because variations among crystalline forms of active pharmaceutical ingredient (API) can lead to changes in the efficacy and safety of formulated product. Such conversions are very hard to be detected, thus, the development of techniques for the identification, characterization and quantification of polymorphs results essential in all stages of the manufacturing process. The presence of excipients in formulated products may change the crystal stability of an API, by catalyzing a polymorphic transformation or stabilizing the less stable form. As paradox, all suitable analytical techniques (spectroscopies, thermal analysis, NMR and DRX, and others) for polymorphic analysis are affected by excipients. A deep understanding of the polymorphism-excipient relationship is in full accordance with Quality by Design (QbD) paradigm, the systematic approach focused in quality building into a product based in the full understanding of the products and process. In this work, a novel approach based on thermal stress, MIR monitoring, multivariate curve resolution with alternating least squares (MCR-ALS) and kinetic analysis was developed and applied to monitor polymorphism behavior of model API in formulated products. Commercial tablets, physical mixtures and commercial API, were processed and analyzed under the proposed approach. Commercial tablets of MFA revealed a fast conversion to Form II, contrasting to the behavior of the pure API. Physical mixtures showed similar behavior to commercial tablets, thus reduction in transformation times was related to MFA-excipients physical interaction, even at surface level. Calorimetric studies support the conclusion obtained. The developed approach could be extended to others APIs and other stress sources (humidity, solvents, mechanical forces and its combinations), being a valuable tool for QbD environment.

Electro-transformation of mefenamic acid drug: a case study of kinetics, transformation products, and toxicity.

Poor removal of many pharmaceuticals and personal care products in sewage treatment plants leads to their discharge into the receiving waters, where they may cause negative effects for aquatic environment and organisms. In this study, electrochemical removal process has been used as alternative method for removal of mefenamic acid (MEF). For our knowledge, removal of MEF using electrochemical process has not been reported yet. Effects of initial concentration of mefenamic acid, sodium chloride (NaCl), and applied voltage were evaluated for improvement of the efficiency of electrochemical treatment process and to understand how much electric energy was consumed in this process. Removal percentage (R%) was ranged between 44 and 97%, depending on the operating parameters except for 0.1 g NaCl which was 9.1%. Consumption energy was 0.224 Wh/mg after 50 min at 2 mg/L of mefenamic acid, 0.5 g NaCl, and 5 V. High consumption energy (0.433 Wh/mg) was observed using high applied voltage of 7 V. Investigation and elucidation of the transformation products were provided by Bruker software dataAnalysis using liquid chromatography-time of flight mass spectrometry. Seven chlorinated and two non-chlorinated transformation products were investigated after 20 min of electrochemical treatment. However, all transformation products (TPs) were eliminated after 140 min. For the assessment of the toxicity, it was impacted by the formation of transformation products especially between 20 and 60 min then the inhibition percentage of E. coli bacteria was decreased after 80 min to be the lowest value.

Multicomponent Crystal of Mefenamic Acid and N-Methyl-d-Glucamine: Crystal Structures and Dissolution Study.

A novel multicomponent crystal (MC) of mefenamic acid (MA) and N-methyl-d-glucamine (MG) had been prepared to improve the physicochemical properties of poorly soluble drugs, and was characterized for its physicochemical properties by powder X-ray diffraction analysis, differential scanning calorimetry thermal analysis, FT-IR spectroscopy, in vitro dissolution rate, and physical stability. In addition, the crystal structure was determined by single-crystal X-ray diffraction analysis. The differential scanning calorimetry thermogram of the MA-MG binary system exhibits a single and sharp endothermic peak at 151.20°C, which was attributed to the melting point of a MC of MA-MG. FT-IR spectroscopy analysis showed the occurrence of solid-state interaction by involving proton transfer between MA and MG. The crystal structure analysis confirmed that MA-MG formed 1:1 ratio salt type MC. The formation of a MC of MA with MG significantly improved the dissolution rate of MA in compared to intact MA, and also the crystal demonstrated a good stability under a high relative humidity. These good properties would be attributed to the layer structure of MA and MG in the crystal.