Blast-induced traumatic brain injury is a significant health concern among military personnel and civilians exposed to explosive devices. Although analgesics are routinely used in laboratory animal studies, their effects on neuroendocrine and neuropathological responses to blast remain insufficiently understood. This study investigated how preinjury administration of buprenorphine (BUP) or meloxicam (MEL) modulates hypothalamic-pituitary-adrenal axis activation, axonal injury, tau phosphorylation, and astroglial responses following blast exposure. Male Sprague Dawley rats were assigned to sham, blast, blast + MEL, or blast + BUP groups and subjected to two tightly coupled ∼19-psi blast waves using an advanced blast simulator. Serum corticosterone and adrenocorticotropic hormone (ACTH) levels and cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy chain (pNFH) were quantified on days 1 and 30, alongside regional (cortex, hippocampus, cerebellum, brainstem) protein expression of pNFH, pTau (Ser396), and glial fibrillary acidic protein (GFAP). Repeated blast exposure caused strong acute elevations in corticosterone, ACTH, and pNFH. BUP suppressed both hormones, whereas MEL selectively reduced ACTH. Both analgesics significantly attenuated acute increases in pNFH, while MEL further mitigated chronic regional elevations in pNFH and GFAP, indicating stronger long-term suppression of axonal and astroglial pathology postblast. Tau hyperphosphorylation was predominantly an acute event, with MEL producing modest region-specific reduction. Region-dependent analyses revealed persistent cortical and brainstem axonal injury, biphasic hippocampal responses, and minimal cerebellar involvement. By day 30, endocrine and CSF biomarkers showed biochemical normalization in analgesic-treated animals but remained elevated in untreated blast-exposed rats. Our findings indicate that routine laboratory analgesics substantially modulate key biomarkers of blast-induced neurotrauma, introducing methodological and interpretive confounds that can impact cross-study reproducibility. Thus, the study should be interpreted primarily as evidence of analgesic-induced biomarker modulation rather than therapeutic neuroprotection.

NMR crystallography, which is based on both diffraction- and solid-state NMR-based observables, can deliver a precise description of the crystal structure of powdered samples of pharmaceuticals. On the other hand, it is by no means a straightforward technique, not least because of the overcrowding of solid-state NMR spectra and difficulties in reliably assigning all resonances, even when advanced 2D techniques are applied. In this work, we showcase the advantages of using very high magnetic field spectrometers in NMR crystallography to solve the structural puzzles posed by four new binary forms of meloxicam (MLX), an anti-inflammatory drug. In particular, we revealed a hidden disorder in the scXRD-determined crystal structure of one of the polymorphic forms of MLX with pyrazole (POL). In this instance, we discovered, through the use of 15N solid-state NMR data, that there is an exchange between two possible tautomeric forms, and by calculating the weighted average of 15N shielding constants, we determined the occupancy of the disordered sites to be 70:30. For the next two binaries, with pyrazine (MLX:PNA) and imidazole in a 1:2 ratio (MLX:IMI 1:2), we solved their crystal structures from powder XRD data and determined the protonation state mainly through the use of quadrupolar product (PQ) of 14N, derived from 1H-14N T-HMQC experiments recorded at two different magnetic field strengths. The signal assignment was done with a set of 1H-1H DQ-SQ Back-to-Back, 1H-13C and 1H-15N HETCOR experiments. For MLX:PNA, we found a very unusual tautomer of MLX inside this crystal, the one which has not been found in any other MLX forms discovered so far. For MLX:IMI 1:2, we established it to be an ionic cocrystal. Finally, for the second MLX binary with imidazole in 1:1 ratio (MLX:IMI 1:1), we used solid-state NMR data to first unambiguously prove that this is a salt and that it comprises one of the two possible tautomers of the MLX anion. This enabled reliable crystal structure prediction calculations for this form, leading to its final crystal structure through Rietveld refinement against the experimental powder XRD pattern.

Background/Objectives: Meloxicam (MLX) is a nonsteroidal anti-inflammatory drug (NSAID) recommended for treating acute and chronic pain in dogs, frequently administered prophylactically to mitigate postoperative pain; however, its utility is limited by characteristic NSAID-associated adverse effects, such as gastrointestinal side effects. Nanosystems offer the potential to minimize adverse effects by sustaining drug release. Therefore, this study assessed the pharmacokinetics of MLX nanoencapsulation in female dogs undergoing ovariohysterectomy using a population pharmacokinetic (PopPK) modeling approach. Methods: MLX-loaded polymeric nanocapsules (NC-MLX) were prepared using the nanoprecipitation method and characterized by zeta potential, pH, mean diameter, particle size distribution, and drug content. Dogs received 0.2 mg/kg of either NC-MLX or free MLX orally, 4 h before surgery, and plasma samples were analyzed using an HPLC-PDA method. Pharmacokinetics were characterized by non-compartmental analysis and PopPK modeling. Several compartmental structures, variability models, and residual error models were explored, and relevant covariates were investigated. Results: NC-MLX had an average diameter of 326 ± 13 nm, a zeta potential of -26.2 ± 6.4 mV, and drug loading of 99.47% ± 0.01%. NC-MLX showed a significant increase in the t1/2 (36.99 ± 17.26 h) of MLX compared to the free drug (15.22 ± 4.4 h). The best-fitting PopPK model was a two-compartment model with double extravascular first-order absorption rate constants (Ka1 and Ka2), including a lag time for Ka2 and linear elimination, describing the second peak observed in several animals. The nanoformulation was a significant covariate for Tlag2, delaying the time for absorption (1.22 and 2.55 h for free MLX and NC-MLX, respectively) and increasing V2 (0.134 and 0.402 L/kg for free MLX and NC-MLX, respectively). External model validation showed that the final PopPK model accurately predicted plasma concentrations, with MPE% and RMSE values below 15%. Conclusions: Our findings suggest that NC-MLX alters MLX absorption and distribution profiles, supporting its potential as an alternative for postoperative pain management in dogs.

Hexagonal bipyramidal Fe-MIL confined grown on network magnetic P-doped biochar: Efficient co-adsorption of As(V) and meloxicam.

Drug-drug pharmaceutical multicomponent materials (PMMs) offer a promising strategy to modulate the physicochemical properties of active pharmaceutical ingredients, while enabling synergistic effects and combination therapy. Here, we report the preparation and full characterization of a new family of oxicam-metformin (MTF) salts, involving the nonsteroidal anti-inflammatory drugs piroxicam (PRX), meloxicam (MLX), and tenoxicam (TNX). Structural and computational studies revealed the role of supramolecular synthons in directing the salt formation and highlighted the relationship between molecular packing and physicochemical properties. Stability analyses showed that these materials enhance MTF stability, while particularly protecting PRX from hydration. Importantly, incorporation of MTF increased the aqueous solubility of the oxicams, while salt formation moderated the excessive solubility of free MTF. Significant modifications in fluorescence behavior were also observed, arising from interactions between functional groups involved in the fluorescence procedure within the frameworks. Overall, this study broadens the structural and functional landscape of oxicam-MTF salts and provides a rational framework for designing solid forms with improved stability and solubility.

This study presents a co-spray drying formulation approach to enhance the dissolution rate of meloxicam (MX), a poorly soluble model drug, by combining it with chitosan (CHIT) and sodium lauryl sulfate (SLS). Ternary formulations were prepared using both mini- and medium-scale spray dryers and compared with physical mixtures and RAW MX. In vitro dissolution testing revealed a significant increase in the release rate, with up to 80% of MX dissolved within 5min. A comprehensive set of solid-state analytical techniques (XRPD, FTIR, and confocal Raman microscopy) revealed subtle changes in MX crystallinity and hydrogen-bonding interactions with both excipients. These findings support three key mechanisms contributing to enhanced dissolution: (i) reduced agglomeration of MX via adsorption onto the CHIT surface, (ii) improved wettability of products due to the presence of SLS, and (iii) increased matrix hydrophilicity facilitating drug-medium contact. The successful scale-up using a medium-scale spray dryer demonstrated the feasibility of this strategy for industrial application. The results highlight co-spray drying with functional excipients as a robust and scalable method for improving the biopharmaceutical performance of poorly soluble drugs. The simple co-spraying of the CHIT dispersion with the drug solution, without the need to dissolve the chitosan, is additional advantage.

This work demonstrates simple and reliable spectrophotometric methods for the simultaneous determination of paracetamol (PAR) and meloxicam (MEL) in mixture I as well as PAR and domperidone (DOM) in mixture II in bulk form and laboratory-made tablets. Successful determination of mixture I was accomplished using direct zero-order spectrophotometry at 361 nm for MEL and first-order derivative (1D) spectrophotometry by measuring the peak at 342 nm and the trough at 262 nm for MEL and PAR respectively. On the other hand, a ratio difference method was suggested for the analysis of mixture II. The difference between the ratio spectra amplitudes at 256 and 288 nm were recorded for PAR determination, and 216 and 288 nm for DOM quantitation using 50 µg/mL DOM and PAR respectively as divisors. The efficacy of the proposed procedures was assessed using ICH criteria for linearity, ranges, precision, accuracy, detection, and quantitation limits. With regard to mixture I, the calibration curves showed linearity in the ranges of 3–30 µg/mL for MEL (zero-order method) and 2.5–30 and 3–15 µg/mL for MEL and PAR, respectively (first-order method), with correlation values of at least 0.9991.Whereas for mixture II, with correlation coefficients of 0.9999, the calibration curves for PAR and DOM were linear in the ranges of 3–70 and 2.5–15 µg/mL, respectively.The established procedures were used to analyze the combinations in the lab-prepared pills, and assay results were compared with reported methods. Greenness of the devised spectrophotometric procedures was assessed using the Analytical Eco-Scale and the Analytical Greenness metric (AGREE).Supplementary InformationThe online version contains supplementary material available at 10.1186/s13065-025-01643-7.

Abstract Meloxicam (MEL) is a nonsteroidal anti‐inflammatory medication with antipyretic, anti‐inflammatory, and analgesic properties. Establishing a sensitive and reliable method to monitor MEL in pharmaceutical formulations is critical to ensure dosing accuracy and guarantee therapeutic efficacy. Herein, a simple electrochemical method was developed for the determination of MEL levels using a TiO 2 ‐Ag‐reduced graphene oxide (TiO 2 ‐Ag‐rGO) nanocomposite‐modified electrode in pH 3.0 Britton–Robinson (BR) buffer via the differential pulse voltammetric (DPV) technique. The prepared TiO 2 ‐Ag‐rGO nanocomposite was characterized by scanning electron microscopy (SEM), X‐ray diffractometer (XRD), and X‐ray photoelectron spectroscopy (XPS) to analyze its morphology, structure, and composition. It was then coated onto a glassy carbon electrode (GCE) surface to construct the TiO 2 ‐Ag‐rGO/GCE. On this modified electrode, the oxidation peak current of MEL centered at 0.65 V showed a notable improvement and was linear with MEL concentrations ranging from 0.5 to 150 μM using optimal parameters. The detection limit calculated for MEL was 15.2 nM (S/N = 3). Application of the method for the assay of MEL in the commercially available tablets form, acceptable deviation from the stated concentration and satisfactory accuracy were obtained.

Fabrication of S-scheme heterojunction consisting of W-doped BiVO4 and biperovskite Cs2AgBiBr6 for photocatalytic degradation of antibiotics.

Oxicams, a major category of nonsteroidal anti-inflammatory drugs, are widely used in daily life. However, excessive consumption of oxicams can pose significant risks to human health. Herein, we introduce an innovative and highly sensitive fluorescent approach for the detection and discrimination of oxicams. This proposed method utilizes the fluorine and nitrogen codoped carbon dots, which display a bright blue emission with two excitation peaks at 280 and 340 nm, synthesized via a hydrothermal method. The variation in the ratio of excitation intensities, measured at a constant emission wavelength, exhibits a linear relationship with the concentration of oxicams. To validate the feasibility of this approach, meloxicam (MLX) is selected as the model compound. The method demonstrates high sensitivity, achieving a low limit of detection (LOD) of 97 nM across a broad concentration span from 0.097 to 25 μM. Moreover, after comparing various machine learning algorithms, the XGBoost algorithm is identified as the optimal choice for discriminating oxicams at ultralow concentrations (0-3.5 μM), with 100% accuracy for unknown samples outside the data sets. Finally, a convolutional neural network (CNN) algorithm-assisted sensing platform has been successfully implemented for the accurate prediction of oxicams in real samples. In summary, this study broadens the application horizon of carbon dots in sensing technologies and offers a viable strategy for real-time monitoring of oxicams, ultimately benefiting public health.

Differential effects of flunixin meglumine and meloxicam on TNF- α production in LPS-stimulated equine neutrophils in vitro

Background: The low solubility of Meloxicam (MX) necessitates preformulation strategies like hydrotropism to enhance it solubility and dissolution rate. Oral dispersible tablets (ODTs) give an alternative for patients with difficulty in swallowing, improving compliance and bypassing the first-pass effect. Many ODT manufacturing techniques, including lyophilization, aims to optimize MX’s therapeutic performance.  Methods: Five physical mixtures were prepared in five different ratios of MX to excipients (HPMC-E15, glycine, sodium benzoate, poloxamer-188 and mannitol). Comparative solubility analysis of (MX) was also conducted using different concentrations of different hydrotropic agents (sodium benzoate, sodium acetate, and urea). MX ODTs were prepared via lyophilization using mannitol as the matrix former and glycine as a protectant. The optimal formulation was selected and enhanced with a hydrotropic agent to improve MX solubility. Tablets were evaluated for physical properties, disintegration, dissolution, and drug content uniformity to ensure pharmacopeial compliance. In addition to FTIR and DSC tests which were conducted on the selected (MX) oral dispersible tablet formulation. Results: Solubility analysis identified sodium benzoate (30% m/v) as an effective hydrotropic agent for (MX) solubilization, facilitating the formulation of lyophilized tablets. After multiple trials incorporating HPMC-E15, Carbomer-934, Poloxamer-188, and mannitol as a diluent, three formulations (F5, F9, and F10) exhibited acceptable characteristics post-lyophilization. Among them, F5 (HPMC-E15 3%, Poloxamer-188 1%) demonstrated superior performance and was subsequently modified to F11 by incorporating 30% sodium benzoate to assess its impact on MX dissolution. One-way ANOVA of the drug release profile at 2 minutes indicated a significant enhancement, with F11 achieving 40.4±2.9% release compared to 18.6±1.9% for F5. Conclusion: The F11 demonstrated an enhanced dissolution rate, indicating the positive effect of the hydrotropic agent (sodium benzoate) on the solubility of MX.

Background: Aqueous solubility of pharmaceuticals is a factor as it is directly associated with bioavailability; accordingly, strategies to enhance solubility have been well investigated. Objectives: The purpose of this study was to determine the effects of coamorphization on meloxicam (MX) and saccharine (SA) mixtures. Methods: An equimolar mixture of MX and SA was ground for 4 h at 300 rpm. The obtained samples were evaluated using Fourier-transform mid-infrared spectroscopy, Fourier transform near-infrared spectroscopy, powder X-ray diffraction (PXRD), and thermal analysis. No molecular interactions were observed in the physical mixture sample. The ground samples showed broad peaks in the PXRD patterns and an exothermic peak at an early temperature. Results: The results suggested that the grinding process transformed MX and SA into a coamorphous phase. The attenuated total reflection - IR spectra exhibited new peaks at 1719 cm-1 and 1398 cm-1, and the NH peak disappeared with grinding time. Measurement data of MX and SA ground sample suggested they constructed coamorphous phase. Conclusion: It was indicated by multivariate analysis that the formation of the MX/SA coamorphous system occurred in a two-step process.

This review discusses the analytical methods used to quantify meloxicam (MLX). It comprehensively surveys the accuracy of current techniques, including spectrophotometry, chromatography, electrochemistry, and other techiques, for meloxicam (MLX) determination. These well-established methods have been successfully applied to diverse sample types, such as pharmaceutical formulations and biological samples like plasma and muscle. A nonsteroidal anti-inflammatory medication (NSAID) called meloxicam MLX commonly prescribed for the management of pain and inflammation associated with various arthritic conditions, is available in multiple formulations, including injections, tablets, and gels. Classified as a derivative of oxicam and structurally related to piroxicam, meloxicam (MLX) belongs to the enolic acid class of compounds developed by Boehringer Ingelheim. Marketed under the trade name Mobic, its properties are similar to those of aspirin as an analgesic.

Meloxicam (MLX), a member of the non-steroidal anti-inflammatory drugs (NSAIDs), is a preferential inhibitor of cyclooxygenase-2 (COX-2) responsible for the synthesis of pro-inflammatory prostaglandins. MLX, due to its inhibition of the COX-2 enzyme, which is overexpressed in many cancers, including melanoma, leading to rapid growth, angiogenesis, and metastasis, represents a potentially important compound with anticancer activity. This study aimed to investigate the potential anticancer activity of meloxicam against amelanotic C32 and melanotic COLO 829 melanoma cell lines. The objective was achieved by assessing cell metabolic activity using the WST-1 assay and analyzing mitochondrial potential, levels of reduced thiols, annexin, and caspases 3/7, 8, and 9 by imaging cytometry, as well as assessing reactive oxygen species (ROS) levels using the H2DCFDA probe. The amelanotic melanoma C32 was more sensitive to MLX exposure, thus exhibiting antiproliferative effects, a disruption of redox homeostasis, a reduction in mitochondrial potential, and an induction of apoptosis. The results provide robust molecular evidence supporting the pharmacological effects of MLX, highlighting its potential as a valuable agent for in vivo melanoma treatment.

Background/Objectives: Chronic lung diseases are among the leading causes of death worldwide. In the treatment of these diseases, non-steroidal anti-inflammatory drugs can be effective. We have previously developed an excipient formulation alongside a modern manufacturing protocol, which we aim to further investigate. We have chosen two new model drugs, meloxicam (MX) and its water-soluble salt, meloxicam-potassium (MXP). The particles in dry powder inhaler (DPI) formulation were expected to have a spherical shape, fast drug release, and good aerodynamic properties. Methods: The excipients were poloxamer-188, mannitol, and leucine. The samples were prepared by spray drying, preceded by solution preparation and wet grinding. Particle size was determined by laser diffraction, shape by scanning electron microscopy (SEM), crystallinity by powder X-ray diffraction (PXRD), interactions by Fourier-transform infrared spectroscopy (FT-IR), in vitro drug dissolution by paddle apparatus, and in vitro aerodynamic properties by Andersen cascade impactor and Spraytec® device. Results: We achieved the proper particle size (<5 μm) and spherical shape according to laser diffraction and SEM. The XRPD showed partial amorphization. FT-IR revealed no interaction between the materials. During the in vitro dissolution tests, more than 90% of MX and MXP were released within the first 5 min. The best products exhibited an aerodynamic diameter of around 4 µm, a fine particle fraction around 50%, and an emitted fraction over 95%. The analysis by Spraytec® supported the suitability for lung targeting. Conclusions: The developed preparation process and excipient system can be applied in the development of different drugs containing DPIs.

Pharmacokinetic evaluation of meloxicam following intravenous and intramuscular administration in Crocodylus siamensis, a freshwater crocodile.

Meloxicam (MLX) is a non-steroidal anti-inflammatory drug that has low bioavailability when administered orally due to its low solubility, and efforts have been made to improve drug delivery to improve solubility. The aim of this study was to prepare and characterize Meloxicam nanocrystals (MLX-NC) and evaluate them with the addition of polyvinylpyrrolidone K-60 (PVP K-60) and decyl glucoside (DG) to prevent nanoparticle aggregation. MLX-NC preparation by a combination of ultrasonic homogenization and the freeze-drying method. The particle size analysis results ranged from 9.76 to 12.73 nm with a polydispersity index &lt;0.5, indicating a homogeneous and stable size distribution. PXRD and DSC characterization revealed the disappearance of the characteristic crystalline peaks of MLX, indicating a transformation to an amorphous form. Additionally, based on saturated solubility studies, the solubility of MLX-NC increased by up to 173 times compared to pure MLX. This study shows that the formulation, initially intended as nanocrystals, resulted in an amorphous solid dispersion due to the influence of stabilizer concentration. This transformation, along with reduced particle size, contributed synergistically to the enhanced solubility of MLX.

Osteoarthritis (OA) is the common form of chronic joint disease. The disease progression can affect all joints of the body, seriously affecting patients’ quality of life. The most effective clinical treatment for OA at the moment is the oral or intravenous administration of non-steroidal anti-inflammatory drugs, such as meloxicam (MX). However, certain challenges associated with the conventional use of those drugs include long dosing cycles, poor patient compliance, and systemic toxic side effects, primarily gastrointestinal reactions. Joint synovial fluid mainly consists of sodium hyaluronate (HA). In recent years, HA has been developed and used to treat OA with local injections. However, it also faces the limitations of short injection cycle, frequent administration, and increases the risk of exogenous infection. In this study, a microsphere gel formulation containing PL407, HA and meloxicam microspheres was prepared and the MX-MS-Gel system showed good performance, syringeability and stability. The results of in vitro release studies showed that the MX-MS-Gel released 8.6% in vitro at 72 h and 28.0% at 480 h, with a more moderate drug release. By injecting iodoacetic acid into the knee joint of rats to establish an OA model, MX-MS-Gel significantly improved the inflammatory response of OA, while the safety of MX-MS-Gel was superior and evaluated in this study, which was safe. The results showed that MX-MS-Gel could realize the purpose of delaying the drug release rate and reducing the frequency of administration, thus improving patient compliance and medication safety.Graphical

A novel hierarchical porous ZIF-8 for effective removal of three non-steroidal anti-inflammatory drugs simultaneously from environment.