Metaxalone Research Articles

APPLICATION OF VALIDATED RP-HPLC METHOD FOR SIMULTANEOUS DETERMINATION OF METAXALONE AND DICLOFENAC POTASSIUM IN PLASMA

Objective: The present investigation demonstrates a simple, sensitive and accurate high-pressure liquid chromatographic (HPLC) method for simultaneous determination of metaxalone (MTX) and Diclofenac potassium (DIC) in plasma by using Valsartan (VSN) as internal standard. Methods: The chromatographic separation was achieved within 10 min by using methanol: potassium dihydrogen phosphate buffer pH 4.5 adjusted with orthophosphoric acid (60:40) as mobile phase on Altima Grace Smart C-18 column (5μ; 250×4.6 mm) at flow rate of 1.0 ml/min with injection volume 25µl. The drug was extracted from plasma by liquid-liquid extraction using methanol as a solvent. The retention times of drugs (MTX and DIC) and internal standard were found to be 5.83, 9.65 and 11.79 min, respectively. This method was validated as per United States Food and Drug Administration (US-FDA) guidelines. Results: The results of the validation parameters were found to be within the acceptance limits. The method was linear in the concentration range from 25-1000 ng/ml (r2= 0.9998) and the extraction recovery was found to be 77.06% for MTX and 78.37% for DIC. The lower limit of quantification was found to be 25ng/ml and the stability of recovered samples at different conditions were found to be more than 95% for both the drugs. Conclusion: The developed method possesses good selectivity specificity, there was no interference found in the plasma blanks at retention times of MTX and DIC. We found good correlation between the peak area and concentration of the drug under prescribed conditions. Furthermore, the method can also be used to estimate the pharmacokinetic parameters of MTX and DIC simultaneously.

Pioneer electrochemical approach for the determination of Metaxalone in biomedical and environmental samples using W: TiO2/S-GCN@CPE sensor

This study focuses on developing a rapid, easy-to-use, and sensitive sensor for the electroanalytical detection of Metaxalone (MXL) for the first time. A novel sensor was created by combining sulfur-incorporated graphitic carbon nitride (S-GCN) with tungsten-doped titanium oxide nanoparticles (W: TiO2 NPs) in a carbon paste, which was then loaded into a polytetrafluoroethylene (PTFE) tube. The synthesized modifiers were characterized using SEM, XRD, and FTIR techniques to understand their structural, morphological, and functional features, contributing to the electrocatalytic activity of the modified sensor (W: TiO2/S-GCN@CPE). Comparative analysis showed that W: TiO2/S-GCN@CPE achieved higher detection currents than the unmodified carbon paste electrode (CPE). Cyclic voltammetry (CV) and square wave voltammetry (SWV) were used to detect and quantify MXL electrochemically. The electrode’s physicochemical properties were studied under optimal conditions within a potential range of 0.3 V to 1.5 V. The W: TiO2/S-GCN@CPE showed a detection limit of 0.85 x 10-8 M and demonstrated linearity over a concentration range of 0.1–100 x 10-7 M. The sensor’s selectivity against interference from metal ions was also assessed. In practical applications, the developed electrode effectively detected MXL in spiked water, tablets, and biological samples, showing significant detection capacity and good recovery rates. Additionally, the electrode demonstrated stability across multiple measurements, positioning W: TiO2/S-GCN@CPE as a promising sensor for MXL detection.

Metabolic activation and cytotoxicity of metaxalone mediated by cytochrome P450 enzymes and sulfotransferases

Metaxalone (MTX) is a central nervous system (CNS) depressant used for the treatment of acute skeletal muscle pain. Several cases of fatal overdose deaths in the clinical use of MTX, along with the presence of ischemic hepatitis in deceased patients, have been documented. The present study aimed to investigate the metabolic activation of MTX and to define the possible correlation between the metabolic activation and cytotoxicity of MTX. An oxidative metabolite (M1) and a GSH conjugate (M2) were observed in S9 fraction incubations as well as in rat primary hepatocyte culture after exposure to MTX. M1 and M2 were also observed in bile of MTX-treated rats. CYP2A6 was found to dominate the oxidation of MTX. Both methoxsalen (MTS, a CYP2A6 inhibitor) and 2,6-dichloro-4-nitrophenol (DCNP, a sulfotransferase inhibitor) dramatically decreased the formation of M2. Pre-treatment of primary hepatocytes with DCNP or MTS significantly decreased the susceptibility to the cytotoxicity of MTX.

Structural and thermal analyses of metaxalone cocrystals with succinic, adipic and salicylic acids

Metaxalone (MTX) is a skeletal muscle relaxant drug, crystallized with carboxylic acid coformers like succinic acid (SUC), adipic acid (ADP) and salicylic acid (SAL). Their molecular structure, crystal packing and thermal analysis were studied. In the crystallization screening, two polymorphic forms of MTX-SAL were discovered. Form I of MTX-SAL was obtained from ethanol while form II was obtained concomitantly along with form I in ethyl acetate. All four structures form MTX homodimer of R22(8) motif. In MTX-SUC, the N-H⋅⋅⋅O, O-H⋅⋅⋅N and C-H⋅⋅⋅O hydrogen bonds are involved in the crystal packing and generate a three-dimensional hydrogen-bonded network. In MTX-ADP, the coformer bridges the adjacent MTX homodimers and forms an extended chain. In both the polymorphs of MTX-SAL, the MTX molecule forms a homodimer, which is further connected by SAL coformer. Solvent assisted grinding and slurry techniques were employed to obtain phase pure bulk material. The results obtained in different trials were compared using powder X-ray diffraction (PXRD) and the process was optimized for bulk solid form preparation of MTX-SUC, MTX-ADP and MTX-SAL form I. MTX-SUC exhibits a higher melting point than the other two cocrystals. The close packing indices, crystal densities and melting temperatures between both the MTX-SAL cocrystal polymorphs resulted in the concomitant existence of form II with form I.

Racemic Conglomerate Formation via Crystallization of Metaxalone from Volatile Deep Eutectic Solvents

The pharmaceutical metaxalone (MTX) was obtained as a conglomerate Form A-R/S, via a newly reported crystallization method exploiting volatile deep eutectic solvents. Homochiral crystals of Form A-...

Optimization of Composition and Process for Preparing Metaxalone Nanosuspension using Factorial Design

In the current study, the composition and process for preparing the nanosuspension of metaxalone (MX) has been optimized by using design of experiments (DOE). MX is skeletal muscle relaxant and belongs to BCS class II1 , the class wherein invivo drug dissolution is a rate-limiting step for drug absorption2 . High pressure homogenization (HPH) method was used to prepare the nanosuspension and Hydroxy propyl methyl cellulose (HPMC) and sodium lauryl sulfate (SLS) as surface stabilizers. For optimization studies three square (32 ) factorial design was used. For the composition optimization, concentration of the stabilizers and for process optimization homogenization time and pressure are used as independent variables. The dependent variables were particle size (PS), polydispersity index (PDI), zeta potential (ZP). The relationship between the dependent and independent variables was studied by response surface plots and contour plots. From the data it has been observed that 2.5 % HPMC, 0.5 % SLS were optimum concentrations and 1000 bar pressure, 120 minutes of homogenization were optimum process conditions producing least PS, PDI and high zeta potential. The optimized nano composition prepared by using optimum process conditions was observed to release more than 80 % within 30 minutes and found to be stable after 3 months of storage at room temperature. The solid state characterization (XRD, DSC) data of spray dried nanoparticles of the optimized composition has shown retention of drug crystallinity. IR has shown drug is compatible with the excipients used. SEM photograph has shown spherical drug nanoparticles. The optimization studies by applying the DOE resulted in considerable decrease in the experimentation work to achieve the stable nanosuspension with desired parameters such as PS, PDI and ZP.

Simplistic Application of 3-Methy-2-Benzothiazoline Hydrazone (MBTH),an Oxidative Coupling Chromogenic Reagent for Quantification ofMetaxalone and Dabigatran Etexilate Mesylate Bulk Drug and Their Dosage Forms

Purpose: A simple and sensitive spectrophotometric method in visible region has been developed and validated for quantification of metaxalone (MET) and dabigatran etexilate mesylate (DAB) in their bulk and pharmaceutical dosage forms. Methods: The method is based on the oxidative coupling reaction of 3-methyl-2-benzothiazoline hydrazone (MBTH) with MET and DAB in the presence of ferric chloride to form green coloured chromogen with absorption maximum at 666 nm and 632 nm respectively. Results: Beer’s law is obeyed in concentration range of 4-20 and 1-6 μg/mL for MET and DAB respectively with correlation coefficient of 0.999. Limit of detection and quantification were 0.46 μg/mL and 1.518 μg/mL for MET and 0.0578 μg/mL and 0.298 μg/mL for DAB. When marketed formulations were analyzed, the results obtained by the proposed method were in good agreement with labelled amounts. The developed method was validated statistically as per ICH guidelines. Conclusion: The developed method is simple, sensitive, specific and can be successfully employed in routine analysis of MET and DAB pharmaceutical dosage forms.

APPLICATION OF CHEMOMETRIC RESPONSE SURFACE METHODOLOGY IN DEVELOPMENT AND OPTIMIZATION OF A RP-HPLC METHOD FOR THE SEPARATION OF METAXALONE AND ITS BASE HYDROLYTIC IMPURITIES

Owing to know the complexity in reverse phase high performance liquid chromatography (RP-HPLC) method optimization; i.e., the selection of optimum combination of input variables for achieving the desired separation, a mathematical relationship between the experimental variables with the responses is to be established by response surface methodology. The paper aims to describe the use of the Box–Behnken experimental design to identify the significant variables effects influencing the separation of metaxalone (MTX) and its two base hydrolytic impurities (DP-1 and DP-2) in a stability indicating RP-HPLC method. Influence variables such as column temperature, buffer pH, and buffer concentration, each at three levels were screened for the desirability of responses like theoretical plates, resolution (MTX-DP-1), capacity factor of MTX, tailing factor at 10% (MTX), and analysis time (R t of DP-2). A statistical program (Design Expert 8.0) was used to calculate and optimize the five responses simultaneously by means of a multiple response optimization algorithm. The optimum conditions are established including the robustness of the method using a Box–Behnken design, as part of the validation exercise. 10 mM phosphate buffer with pH 4.7 at 31°C column temperature was found to be the optimized condition to produce desirable responses. System suitability limits were defined based on the results of the robustness test. The RP-HPLC method was further validated with respect to linearity, range, precision, specificity, accuracy, limit of detection, and limit of quantification, according to the current regulatory requirements. The optimized method gives rapid and efficient separation with complete resolution between the three peaks, and represents an improvement over the existing reported methods.

Kinetics study of metaxalone degradation under hydrolytic, oxidative and thermal stress conditions using stability-indicating HPLC method

An isocratic stability indicating RP-HPLC–UV method is presented for the determination of metaxalone (MET) in the presence of its degradation products. The method uses Dr. Maisch C18 column (250mm×4.6mm, 5μm) with mobile phase consisting of acetonitrile–potassium dihydrogen orthophosphate buffer with 4mL of 0.4% triethyl amine (pH 3.0; 10mM) (58:42, v/v) at a flow rate of 1.0mL/min. pH of the buffer was adjusted with o-phosphoric acid. UV detection was performed at 225nm. The method was validated for specificity, linearity, precision, accuracy, limit of detection, limit of quantification and robustness. The calibration plot was linear over the concentration range of 1–100μg/mL having a correlation coefficient (r2) of 0.999. Limits of detection and quantification were 0.3 and 1μg/mL, respectively. Intra-day and inter-day precision (% RSD) was 0.65 and 0.79 respectively. The proposed method was used to investigate the degradation kinetics of MET under different stress conditions employed. Degradation of MET followed a pseudo-first-order kinetics, and rate constant (K), time left for 50% potency (t1/2), and time left for 90% potency (t90) were calculated.

Development of a Stability Indicating RP-UPLC Method for Rapid Determination of Metaxalone and its Degradation Products in Solid Oral Dosage Form

A simple, sensitive and reproducible reversed phase ultra performance liquid chromatography (RP-UPLC) coupled with a photodiode array detector method was developed for the quantitative determination of metaxalone (META) in pharmaceutical dosage forms. The method is applicable to the quantification of related substances and assay of drug product. Chromatographic separation was achieved on an Acquity® HSS-T3 (100 mm x 2.1 mm, 1.7 μm) column. The optimized isocratic mobile phase consists of a mixture of water, methanol, acetonitrile and triethylamine in the ratio of 50:25:25:0.1 % v/v (pH adjusted to 6.3 with orthophosphoric acid). The eluted compounds were monitored at 230 nm for META assay and 205 nm for related substances, the flow rate was 0.3 mL/min, and the column oven temperature was maintained at 45°C. The developed method separated META from its two known and two unknown impurities within 6.0 min. Metaxalone was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Metaxalone was found to degrade significantly in base stress condition, degrade slightly in oxidative stress condition and remain stable in acid, hydrolytic, thermal and photolytic degradation conditions. All impurities were well resolved from each other and from the main peak, showing the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization (ICH) guidelines.

Conformational Polymorphs of a Muscle Relaxant, Metaxalone

Metaxalone (MTX) is a muscle relaxant which is used to relieve pain caused by strains and sprains. MTX has been in the market under the brand name of Skelaxin since 1962, and two polymorphs of MTX were first mentioned in a patent published in 2007. However, their crystal structures, stability relationship, and dissolution profiles have not yet been analyzed. We herein report two conformational polymorphs of racemic MTX with an objective to unravel the structural origin of polymorphism and study their phase transformations, stability, solubility, and dissolution properties. Both forms were obtained concomitantly by cooling crystallization experiments from ethyl acetate. Crystal structure analysis revealed that the MTX molecule adopts different conformations in the polymorphs. Interestingly, the imide group of the MTX forms an imide–imide catemer synthon in Form A and an imide–imide dimer synthon in Form B. Thermal analysis and solubility measurements suggest an enantiotropic relationship between the polymo...

Metabolism of metaxalone.

Metabolism of metaxalone.

Evaluation of Metaxalone

Evaluation of Metaxalone