Concentration Of Mefenamic Acid Research Articles

Green Synthesis of Electroactive Magnesium Ferrite Nanoparticles for the Selective Determination of Mefenamic Acid in Blood, Pharmaceutical Products, and Wastewater

Mefenamic acid (MNA) treats sports injuries, rheumatoid arthritis, and osteoarthritis. However, improper use/disposal of MNA results in the accumulation of toxic metabolites that may serious disease. The purpose of this study is to fabricate a nano ferrite-based electrochemical sensor for robust, and sensitive determination of MNA. Magnesium ferrite nanoparticles (MgFe4O7-NPs) were synthesized using a green approach using a Mentha leaf extract. The analytical characterization of MgFe4O7-NPs displayed a hexagonal structure and a particle size of less than 21 nm with rough and porous morphology. The synthesized MgFe4O7-NPs were used to fabricate an electrochemical sensor by modifying a glassy carbon electrode (MgFe4O7-NPs/GCE). The cyclic voltammetry (CV) characterization of the electrode confirms excellent redox and diffusion control for electroactive species. Thus, the MgFe4O7-NPs/GCE was used to determine MNA by differential pulse voltammetry (DPV). The results showed a linear relationship between oxidation peak current and concentration of MNA from 10 × 10−9 to 2.30 × 10−4 M (R 2 = 0.9918) with a detection limit of 1.12 × 10−9 M. The analytical performance of the fabricated sensor has been evaluated for MNA in blood samples, pharmaceutical tablets, and water samples with satisfactory results.

High Throughput LC-MS/MS Method for the Quantitation of Mefenamic Acid in Rat Plasma by Protein Precipitation Technique Using 96 Well Plate Format

An advanced and validated high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach has been established to accurately determine the concentration of mefenamic acid in rat plasma. This method utilizes mefenamic acid D4 as the internal standard (ISTD). The analyte and ISTD underwent protein precipitation in a 96-well plate format and were then separated on a BDS Hypersil C8 column (3 μm, 100 x 4.6 mm) using a precise isocratic mobile phase of 2 mM ammonium formate by 0.1% formic acid and acetonitrile (30:70 v/v). The detection was performed on a triple quadrupole mass spectrometer utilizing positive ionization consideration. The approach demonstrated a concentration range of 20.659 to 20067.772 ng/mL, thru relative regaining reaching from 69.1 to 74.3%. The inter-batch precision was excellent, with a coefficient of variation (%CV) of ≤ 7.8%. Additionally, the inter-batch accuracy at four different quality control-points ranged from 97.0 to 100.4%, demonstrating high levels of accuracy. This method has been thoroughly validated and is extremely specific, accurate, and precise. It is perfectly suited for high-throughput investigation of mefenamic acid in rat plasma, making it ideal for routine analysis.

Inhibitory Effects of Mefenamic Acid on Rat Urinary Bladder Contractions In Vitro ( Effects of Mefenamic Acid on Urinary Bladder Contractions )

Objective: In this study, the effect of mefenamic acid, a nonsteroidal anti-inflammatory drug, on the unconstrained contractile movement of the bladder muscle of female Spraque Dawley rats in diestrus was investigated. Since the effect of mefenamic acid on bladder smooth muscle is not known and its use for other conditions may cause possible side effects on the bladder, its effect was investigated for the possibility of using it as an active substance in the treatment of bladder problems. Materials and Methods: In the experimental study, 1.5 cm long smooth muscle strips from seven female Sprague Dawley rats were prepared and suspended in an isolated organ bath system containing Krebs solution under 1.5 g tension. The system was gassed continuously with oxygen/carbon dioxide mixture (95%:5%) and isometric contractions were recorded. At a dose of 300 µM, the contraction/relaxation effects of mefenamic acid concentration on bladder smooth muscle were investigated. The area under the curve (AUC) and amplitude values of bladder contractions were analyzed before and after mefenamic acid administration. With the data obtained from the analysis, the effect of mefenamic acid on bladder contractions was evaluated using paired t-tests in SPSS Statistical Software. Results: The decrease in area and amplitude values was statistically significant (P<0.05). Mefenamic acid had an inhibitory effect on bladder contractions. Conclusion: The present findings demonstrate the relaxant effect of mefenamic acid on the rat bladder and if similar effects are observed in human studies, mefenamic acid may be effective in the treatment of voiding problems such as bladder incontinence.

A magnetic sorbent based on Zn-NiFe2O4@Ni-Al layered double hydroxide nanocomposite for the pre-concentration and quantification of mefenamic acid by differential pulse voltammetry

A novel magnetic sorbent was introduced involving a zinc–nickel ferrite@nickel–aluminum layered double hydroxide (Zn-NiFe2O4@Ni-Al LDH) nanocomposite. The Zn-NiFe2O4@Ni–Al LDH was synthesized through a co-precipitation method, and characterized using several techniques. The nanocomposite was shown to be an efficient sorbent for the pre-concentration of mefenamic acid prior to its detection by differential pulse voltammetry using a glassy carbon electrode modified with carbon nanotubes. To achieve the best extraction efficiency, the effects of various parameters such as pH, the sorbent dosage, extraction time, elution conditions, and sample volume were studied and optimized. Under the optimized experimental conditions, the calibration plot was linear in two concentration ranges from 50 to 100 nM (R2 = 0.9944) and 100–700 nM (R2 = 0.9913). The limit of detection was calculated to be 6.3 nM, and the precision of the method in the terms of intra-day and inter-day relative standard deviations (n = 5; mefenamic acid concentration = 100 nM) were 1.4% and 2.4%, respectively. The accuracy of the method was assessed by analyzing a pharmaceutical dosage form of the analyte, and comparing the results with those obtained from a standard method. To evaluate the applicability of the method, it was applied for trace determination of mefenamic acid in tablet, human plasma, urine, and pharmaceutical wastewater samples, and the satisfactory relative recovery values (96.0–103.1%) were attained for the spiked samples. The easy separation from the solution by applying an external magnet, high surface area, high stability in the strong alkaline solutions, and high reusability (more than 60 adsorption/desorption cycles) are some advantages of the synthesized nanosorbent.

Determination of mefenamic acid in aqueous solutions using merging zone – continuous flow injection

AbstractThis research aims at using a novel algorithm to determine the concentration of mefenamic acid (MA) in solutions using merging zone-continuous flow injection. The MA concentration in aqueous solutions was determined using this technology, and the results obtained using this method were compared to those obtained using more conventional methods. All flow injection analyses were carried out utilizing a Rheodyne valve 7725, a Rabbit peristaltic pump, a BioLogic QuadTec UV-Vis Detector, and a Sartorius CPA2P Competence Analytical Balance, as well as a Sartorius CPA2P Competence Analytical Balance. The data is then received by a signal detector and a specialized software spectrometer. A spectroscopic scan is used to determine the maximum wavelength of the product, a calibration curve is created, and measurements are taken to estimate the drug's absolute concentrations in aqueous solutions. The detection and quantitative limits were set to 0.021 and 0.071 parts per million. This treatment is popular and could be a good alternative to conventional methods because it is simple, rapid, precise, inexpensive, and adaptable.

MCR-ALS for Investigating the Effect of Adsorption on the Charging Current; Application for the Voltammetric Determination of Mefenamic Acid on a Glassy Carbon Electrode Modified with MWCNT and Poly L-Proline

This study represents the application of MCR-ALS for the separation of the different sources of variation in a series of the linear sweep voltammograms obtained from the oxidation of the Mefenamic acid as a model analyte on a poly L-proline and MWCNT-modified GCE. Two types of faradaic currents including adsorption and diffusion were separated successfully and the effects of the accumulation time and the concentration of Mefenamic acid were investigated on the variation of the charging current. The results showed that the contribution of the charging current on the measured signal decreases upon increasing the adsorption as a result of the blockage of the electrode active sites with the adsorbed species which is in agreement with the previous studies. The proposed methodology was employed for voltammetric determination of Mefenamic acid with enhanced figures of merit in real serum samples by removing the contribution of the charging current from the measured signal. The obtained results indicate the lower detection limit as 90 nM, wider linear range and higher sensitivity compared to the unprocessed and background-subtracted data.

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 0.1g NaCl which was 9.1%. Consumption energy was 0.224Wh/mg after 50min at 2mg/L of mefenamic acid, 0.5g NaCl, and 5V. High consumption energy (0.433Wh/mg) was observed using high applied voltage of 7V. 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 20min of electrochemical treatment. However, all transformation products (TPs) were eliminated after 140min. For the assessment of the toxicity, it was impacted by the formation of transformation products especially between 20 and 60min then the inhibition percentage of E. coli bacteria was decreased after 80min to be the lowest value.

Voltammetric detection and determination of mefenamic acid at silver-doped TiO2 nanoparticles modified electrode

Abstract A simple sensitive voltammetric method to detect and to determine a nano level anthranilic acid derivative, mefenamic acid has been developed using different voltammetric techniques in pH 5.0 phosphate buffer solutions with ionic strength 0.2M. An enhancement of oxidation peak current for an analyte on the modified paste was observed followed by characterization with atomic mass spectroscopy analysis. The control of various parameters on the drug oxidation current like accumulation time, amount of modifier, pH, scan rate, and concentration was also evaluated. The analytical applications were studied by square wave voltammetry technique. A suitable electro-oxidation mechanism for mefenamic acid at nanoparticles silver-doped titanium dioxide modified carbon paste electrode was proposed. The oxidation peak currents of mefenamic acid concentration was studied using square wave voltammetry technique in the range 1.0 x 10-8 to 3.0 x 10-6 M with a lower detection limit 1.94 nM compared to earlier reported practice. The modified sensor showed an excellent physiological feature, large surface area, remarkable stability, reproducibility by simple preparation process. The proposed method was successfully employed for the determination of mefenamic acid in pharmaceutical and biological samples with good recovery values.

Sensitive Determination of Mefenamic Acid in Biological Fluids and Pharmaceutical Formulations on Carbon Nanotubes Fabricated Sensor

Mefenamic acid (MFA) is a member of fenamate group of non- steroidal anti-inflammatory drug used in the therapy of pain phenomena and blockade of inflammatory areas; for the stimulation of the immune system in patients with arthritis and arthrosis. The degree of menstrual blood loss is reduced with the treatment of MFA and it is also used to treat autoimmune haemolytic anaemia. Measurement of plasma levels of MFA may provide valuable information for MFA treatment in premature infants with symptomatic patent ductus arteriosus and for preventing possible toxic effects. However, the excessive intake of MFA leads to diarrhoea, vomiting, lactic acidosis, hepatic necrosis, liver injury, morbidity and mortality in humans. Consequently, the development of an inexpensive, sensitive and accurate analytical method for determination of MFA is of considerable importance. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed agents worldwide due to their anti-inflammatory, antipyretic and analgesic properties and are usually used in the treatment of inflammatory and degenerative diseases of the articulations. In addition, epidemiological studies have shown that long-term use of NSAIDs reduces the risk of developing Alzheimer disease and delays its onset. This category of drugs alleviate pain by counteracting the cyclooxygenase (COX) enzyme. On its own, COX enzyme synthesizes prostaglandins, creating inflammation. In whole, the NSAIDs prevent the prostaglandins from ever being synthesized, which otherwise lead to an increase of vascular permeability, edema, hyperalgesia, pyrexia, and inflammation. These drugs have also shown to induce various forms of adverse drug reactions, including adverse gastrointestinal effects, renal dysfunction and nephrotoxicity, liver damage, adverse neurological effects, and rhabdomyolysis. Herein, we report the selective and sensitive determination of mefenamic acid on single walled carbon nanotubes modified glassy carbon electrode (GCE) employing square wave voltammetry. The developed sensor exhibited amelioration in the peak current response with a negative shift in the peak potential in comparison to multi walled carbon nanotubes modified GCE and bare GCE. Voltammetric studies indicated the oxidation of MFA at the electrode surface through a one electron and one proton irreversible step and fundamentally controlled by adsorption. A good linear relationship has been found between the anodic peak current and mefenamic acid concentration in the range of 0.1 – 35 µM with limits of quantification and detection as 44.7 and 13.4 nM, respectively. The interfering effect of physiologically common interferents on the current response of mefenamic acid has been reported. Furthermore, the proposed method was successfully applied to the determination of mefenamic acid in pharmaceutical formulations and human plasma samples.

IN SILICO BINDING INTERACTION STUDY OF MEFENAMIC ACID AND PIROXICAM ON HUMAN ALBUMIN

Objective: A drug can replace other drugs in the same binding position in protein plasma, increasing pharmacological response due to the increasedfree drug concentration. Drug shifting is critical when a compound is tightly bound to a protein. For example, a binding fraction change, from 98% to94%, may increase the free fraction 3 times, from 2% to 6%. Knowing that there is an interaction between mefenamic acid and piroxicam on plasmaprotein, more specifically on human albumin, this study aimed to visualize the interaction between both drugs and human albumin in silico.Methods: This study used AutoDock4 as a molecular docking technique, obtaining binding visualizations, binding energies (ΔG), and inhibitionconstants (Ki) of both mefenamic acid-albumin and piroxicam-albumin bindings.Results: It is shown that the ΔG and Ki of both mefenamic acid and piroxicam are −5.47 kcal/mol (98.59 μM) and −7.46 kcal/mol (3.42 μM), respectively.Conclusions: The process of binding mefenamic acid to albumin can be substituted with piroxicam due to its higher ΔG and Ki values. It can bepredicted that this interaction will increase the free mefenamic acid concentration in blood plasma which, in turn, enhances the therapeutic effect.

Enhancement in sensitivity of non-steroidal anti-inflammatory drug mefenamic acid at carbon nanostructured sensor

This article describes the selective and sensitive determination of mefenamic acid on single walled carbon nanotubes modified glassy carbon electrode (GCE) employing square wave voltammetry for the first time. The developed sensor exhibited amelioration in the peak current response with a negative shift in the peak potential in comparison to multi walled carbon nanotubes modified GCE and bare GCE. A good linear relationship has been found between the anodic peak current and mefenamic acid concentration in the range of 0.1–35μM with limits of quantification and detection as 44.7 and 13.4nM, respectively. The interfering effects of the commonly existing metabolites in the biological fluids have been investigated on the current response of the drug. The developed sensor was successfully applied for the assay of mefenamic acid in pharmaceutical formulations. Furthermore, the applicability of the proposed method to determine mefenamic acid in human urine samples obtained from healthy volunteer and patient after 4h of administration of the drug is illustrated.

Development of Nanomaterial Modified Sensor for the Electrocatalytic Oxidation of Non-Steroidal Anti-Inflammatory Drug

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed agents worldwide due to their anti-inflammatory, antipyretic and analgesic properties and are usually used in the treatment of inflammatory and degenerative diseases of the articulations. In addition, epidemiological studies have shown that long-term use of NSAIDs reduces the risk of developing Alzheimer disease and delays its onset. This category of drugs alleviate pain by counteracting the cyclooxygenase (COX) enzyme. On its own, COX enzyme synthesizes prostaglandins, creating inflammation. In whole, the NSAIDs prevent the prostaglandins from ever being synthesized, which otherwise lead to an increase of vascular permeability, edema, hyperalgesia, pyrexia, and inflammation. These drugs have also shown to induce various forms of adverse drug reactions, including adverse gastrointestinal effects, renal dysfunction and nephrotoxicity, liver damage, adverse neurological effects, and rhabdomyolysis. Mefenamic acid, (MFA) 2-(2, 3-dimethylphenyl) amino benzoic acid is a member of fenamate group of non- steroidal anti-inflammatory drug used in the therapy of pain phenomena and blockade of inflammatory areas; for the stimulation of the immune system in patients with arthritis and arthrosis. It is used for the treatment of mild to moderate pain, including headache, dental pain, post-operative and post-partum pain, dysmenorrhoea, as well as musculoskeletal disorders and sport injuries. The degree of menstrual blood loss is reduced with the treatment of MFA and it is also used to treat autoimmune haemolytic anaemia. Measurement of plasma levels of MFA may provide valuable information for MFA treatment in premature infants with symptomatic patent ductus arteriosus and for preventing possible toxic effects. However, the excessive intake of MFA leads to diarrhoea, vomiting, lactic acidosis, purpura, hepatic necrosis, liver injury, acute colitis in patients, morbidity and mortality in humans. Consequently, the development of a simple, inexpensive, sensitive and accurate analytical method for determination of MFA is of considerable importance. Herein, we report the selective and sensitive determination of mefenamic acid on single walled carbon nanotubes modified glassy carbon electrode (GCE) employing square wave voltammetry for the first time. The developed sensor exhibited amelioration in the peak current response with a negative shift in the peak potential in comparison to multi walled carbon nanotubes modified GCE and bare GCE. Voltammetric studies indicated the oxidation of mefenamic acid at the electrode surface through a one electron and one proton irreversible step and fundamentally controlled by adsorption. A good linear relationship has been found between the anodic peak current and mefenamic acid concentration in the range of 0.1 – 35 µM with limits of quantification and detection as 44.7 and 13.4 nM, respectively. The interfering effect of physiologically common interferents on the current response of mefenamic acid has been reported. Furthermore, the proposed method was successfully applied to the determination of mefenamic acid in pharmaceutical formulations and human plasma samples.

Adsorption of Mefenamic Acid From Water by Bentonite Poly urea formaldehyde Composite Adsorbent

Poly urea formaldehyde –Bentonite (PUF-Bentonite) composite was tested as new adsorbentfor removal of mefenamic acid (MA) from simulated wastewater in batch adsorption procedure. Developed a method for preparing poly urea formaldehyde gel in basic media byusing condensation polymerization. Adsorption experiments were carried out as a function ofwater pH, temperature, contact time, adsorbent dose and initial MA concentration .Effect ofsharing surface with other analgesic pharmaceuticals at different pH also studied. Theadsorption of MA was found to be strongly dependent to pH. The Freundlich isotherm modelshowed a good fit to the equilibrium adsorption data. From Dubinin–Radushkevich model themean free energy (E) was calculated and the value of 5 KJ/mole indicated that the mainmechanism governing the adsorption of MA on PUF-Bentonite composite was physical innature. The kinetics of adsorption tested for first order, pseudo second order models andElovich’s equation, results showed the adsorption followed the pseudo-second-order model.

Influence of drug load on dissolution behavior of tablets containing a poorly water-soluble drug: estimation of the percolation threshold

Drug load plays an important role in the development of solid dosage forms, since it can significantly influence both processability and final product properties. The percolation threshold of the active pharmaceutical ingredient (API) corresponds to a critical concentration, above which an abrupt change in drug product characteristics can occur. The objective of this study was to identify the percolation threshold of a poorly water-soluble drug with regard to the dissolution behavior from immediate release tablets. The influence of the API particle size on the percolation threshold was also studied. Formulations with increasing drug loads were manufactured via roll compaction using constant process parameters and subsequent tableting. Drug dissolution was investigated in biorelevant medium. The percolation threshold was estimated via a model dependent and a model independent method based on the dissolution data. The intragranular concentration of mefenamic acid had a significant effect on granules and tablet characteristics, such as particle size distribution, compactibility and tablet disintegration. Increasing the intragranular drug concentration of the tablets resulted in lower dissolution rates. A percolation threshold of approximately 20% v/v could be determined for both particle sizes of the API above which an abrupt decrease of the dissolution rate occurred. However, the increasing drug load had a more pronounced effect on dissolution rate of tablets containing the micronized API, which can be attributed to the high agglomeration tendency of micronized substances during manufacturing steps, such as roll compaction and tableting. Both methods that were applied for the estimation of percolation threshold provided comparable values.

Mixed Micelle System Produced by Interaction Between Transglycosylated Stevia and an Ionic Surfactant Improves Dissolution Profile of Mefenamic Acid

Transglycosylated stevia (stevia-G) can effectively improve the dissolution and bioavailability of poorly water-soluble drugs. Furthermore, addition of an ionic surfactant to stevia-G solution has been shown to enhance the dissolution effect of stevia-G on flurbiprofen. Herein, 4 surfactants, namely sodium dodecyl sulfate, sodium N-dodecanoylsarcosinate, sodium monododecyl phosphate, and lauryltrimethylammonium chloride (LTAC) were screened to investigate their synergistic effect with stevia-G in enhancing the solubility of mefenamic acid (MFA). The ternary formulation containing LTAC produced the highest increase in solubility, whereas the binary MFA/LTAC formulation did not increase the solubility of MFA. Surface tension was evaluated to analyze the interaction between stevia-G and each ionic surfactant, wherein the Rubingh model was applied to predict mixed micelle formation between stevia-G and LTAC. Interaction parameters calculated by the Rubingh model reflected mixed micelle formation between stevia-G and LTAC relative to the self-interactions of the 2 individual surfactants. All interaction parameters in this system showed negative values, indicating a favorable interaction (e.g., hydrogen bond or electrostatic and dipole) between binary components in the mixed micelles. Spray-dried particles of ternary formulations (MFA/stevia-G/LTAC) were prepared to evaluate the dissolution profile and physicochemical properties. Dissolution profiling showed that the concentration of MFA released from spray-dried particles was significantly higher than untreated MFA.

Enhanced photocatalytic activity of supported CuO–ZnO semiconductors towards the photodegradation of mefenamic acid aqueous solution as a semi real sample

The elimination mefenamic acid (MA) as a pollutant from the aquatic environment using Hg lamp during a catalytic photodegradation process using supported ZnO–CuO onto clinoptilolite nanoparticles (NCP) was the aim of the study. Raw and supported clinoptilolite were characterized by FT-IR, XRD, DRS, TEM and SEM techniques. The changes of MA concentration determined by UV–vis double beam spectrophotometer at λmax 285nm and used for the calculation of its degradation extent. Better degradation efficiencies obtained for the supported the hybridized ZnO–CuO system onto NCP with respect to unsupported one and supported/unsupported ZnO and CuO. The degradation efficiencies are dependent to the experimental conditions and hence the parameters were optimized to reach the highest efficiencies.

Insights into Atomic-Level Interaction between Mefenamic Acid and Eudragit EPO in a Supersaturated Solution by High-Resolution Magic-Angle Spinning NMR Spectroscopy

The intermolecular interaction between mefenamic acid (MFA), a poorly water-soluble nonsteroidal anti-inflammatory drug, and Eudragit EPO (EPO), a water-soluble polymer, is investigated in their supersaturated solution using high-resolution magic-angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy. The stable supersaturated solution with a high MFA concentration of 3.0 mg/mL is prepared by dispersing the amorphous solid dispersion into a d-acetate buffer at pH 5.5 and 37 °C. By virtue of MAS at 2.7 kHz, the extremely broad and unresolved (1)H resonances of MFA in one-dimensional (1)H NMR spectrum of the supersaturated solution are well-resolved, thus enabling the complete assignment of MFA (1)H resonances in the aqueous solution. Two-dimensional (2D) (1)H/(1)H nuclear Overhauser effect spectroscopy (NOESY) and radio frequency-driven recoupling (RFDR) under MAS conditions reveal the interaction of MFA with EPO in the supersaturated solution at an atomic level. The strong cross-correlations observed in the 2D (1)H/(1)H NMR spectra indicate a hydrophobic interaction between the aromatic group of MFA and the backbone of EPO. Furthermore, the aminoalkyl group in the side chain of EPO forms a hydrophilic interaction, which can be either electrostatic or hydrogen bonding, with the carboxyl group of MFA. We believe these hydrophobic and hydrophilic interactions between MFA and EPO molecules play a key role in the formation of this extremely stable supersaturated solution. In addition, 2D (1)H/(1)H RFDR demonstrates that the molecular MFA-EPO interaction is quite flexible and dynamic.

Stabilization of a Supersaturated Solution of Mefenamic Acid from a Solid Dispersion with EUDRAGIT® EPO

The stabilization mechanism of a supersaturated solution of mefenamic acid (MFA) from a solid dispersion with EUDRAGIT(®) EPO (EPO) was investigated. The solid dispersions were prepared by cryogenic grinding method. Powder X-ray diffractometry, in vitro dissolution test, in vivo oral absorption study, infrared spectroscopy, and solid- and solution-state NMR spectroscopies were used to characterize the solid dispersions. Dissolution tests in acetate buffer (pH 5.5) revealed that solid dispersion showed > 200-fold higher concentration of MFA. Supersaturated solution was stable over 1month and exhibited improved oral bioavailability of MFA in rats, with a 7.8-fold higher area under the plasma concentration-versus-time curve. Solid-state (1)H spin-lattice relaxation time (T(1)) measurement showed that MFA was almost monomolecularly dispersed in the EPO polymer matrix. Intermolecular interaction between MFA and EPO was indicated by solid-state infrared and (13)C-T(1) measurements. Solution-state (1)H-NMR measurement demonstrated that MFA existed in monomolecular state in supersaturated solution. (1)H-T(1) and difference nuclear Overhauser effect measurements indicated that cross relaxation occurred between MFA and EPO due to the small distance between them. The formation and high stability of the supersaturated solution were attributable to the specifically formed intermolecular interactions between MFA and EPO.

Spectrophotometric assay of mefenamic acid in tablets using 1,4-dioxane as solvent for extraction

A spectrophotometric method of assay of mefenamic acid in tablets involving, dissolving the tablet powder in 1,4-dioxane and measuring the absorbance at 353.2 nm. The concentration of mefenamic acid is determined using the previously prepared calibration curve using standard solution of mefenamic acid in dioxane. The method was tested by assay of six different commercial tablets containing mefenamic acid.

Inactivation of cholinesterase induced by non-steroidal anti-inflammatory drugs with horseradish peroxidase: Implication for Alzheimer's disease

Aims To clarify the mechanism of the protective effect of non-steroidal anti-inflammatory drugs (NSAIDs) on Alzheimer's disease, inactivation of cholinesterase (ChE) induced by NSAIDs was examined. Main methods Equine ChE and rat brain homogenate were incubated with NSAIDs and horseradish peroxidase (HRP) and H 2O 2 (HRP–H 2O 2). ChE activity was measured by using 5,5'-dithiobis(nitrobenzoic acid). By using electron spin resonance, NSAID radicals induced by reaction with HRP–H 2O 2 were detected in the presence of spin trap agents. Key findings Equine ChE was inactivated by mefenamic acid with HRP–H 2O 2. ChE activity in rat brain homogenate decreased dependent on the concentration of mefenamic acid in the presence of HRP–H 2O 2. NSAIDs diclofenac, indomethacin, phenylbutazone, piroxicam and salicylic acid inactivated ChE. Oxygen radical scavengers did not prevent inactivation of ChE induced by mefenamic acid with HRP–H 2O 2. However, spin trap agents 5,5-dimethyl-1-pyrroline-l-oxide and N-methyl-nitrosopropane, reduced glutathione and ascorbic acid strongly inhibited inactivation of ChE, indicating participation of mefenamic acid radicals. Fluorescent emission of ChE peaked at 400 nm, and the Vmax value of ChE changed during interaction of mefenamic acid with HRP–H 2O 2, indicating that ChE may be inactivated through modification of tyrosine residues by mefenamic radicals. Significance The protective effect of NSAIDs on Alzheimer's disease seems to occur through inactivation of ChE induced by NSAIDs radicals.