mobic and lornoxicam

The purpose of the present investigation was to analyze devitrification of amorphous drugs such as lornoxicam, meloxicam, and felodipine in the presence of sericin. The binary solid dispersions comprising varying mass ratios of drug and sericin were subject to amorphization by spray drying, solvent evaporation, ball milling, and physical mixing. Further, obtained solid dispersions (SDs) were characterized by HPLC, ATR-FTIR, H

Topics: Chemistry, Pharmaceutical; Crystallization; Desiccation; Drug Stability; Felodipine; Meloxicam; Molecular Docking Simulation; Piroxicam; Sericins; Solubility; Solvents

The aetiology for nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injuries has not been well characterised.. To determine the risk factors of symptomatic NSAID-induced small intestinal injuries, including diaphragm disease.. Of the 1262 symptomatic patients who underwent videocapsule endoscopy and/or double-balloon enteroscopy, 156 consecutive patients were verified as having taken NSAIDs. Their CYP2C9*2, *3 and *13 single nucleotide polymorphisms (SNPs) were determined by allelic discrimination with Taqman 5'-nuclease assays.. Of the 156 NSAIDs users, 31 patients (20%) were diagnosed with NSAID-induced small intestinal injury. Multivariate analysis indicated that the presence of comorbidities and the use of oxicams (meloxicam, ampiroxicam and lornoxicam) or diclofenac were associated with an increased risk of NSAID-induced small intestinal injury (adjusted OR: 2.97, 95% CI: 1.05-8.41, P = 0.041 and adjusted OR: 7.05, 95% CI: 2.04-24.40, P = 0.002, respectively). The combination of aspirin and non-aspirin NSAID was more damaging than aspirin alone. Age, sex, concomitant use of proton pump inhibitors, indications for NSAIDs use, duration of NSAIDs use and CYP2C9*2, *3 and *13SNPs were unrelated. The use of meloxicam and CYP2C9*3SNPs were significantly associated with an increased risk for diaphragm disease (adjusted OR: 183.75, 95% CI: 21.34-1582.38; P < 0.0001 and adjusted OR: 12.94, 95% CI: 1.55-108.36, P = 0.018, respectively).. The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Aryl Hydrocarbon Hydroxylases; Aspirin; Capsule Endoscopy; Case-Control Studies; Cytochrome P-450 CYP2C9; Diaphragm; Diclofenac; Double-Balloon Enteroscopy; Female; Humans; Intestinal Diseases; Intestine, Small; Male; Meloxicam; Middle Aged; Piroxicam; Polymorphism, Single Nucleotide; Risk Factors; Thiazines; Thiazoles

A high-performance liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique was developed for the simultaneous determination of five non-steroidal anti-inflammatory oxicam drugs (ampiroxicam, tenoxicam, piroxicam, meloxicam and lornoxicam) in human plasma. These five oxicam drugs and isoxicam (internal standard) were extracted from human plasma with an Oasis(®) MAX cartridge column and analysed on a Unison UK-C18 column (2.0 mm × 100 mm, 3 μm) with an acetonitrile:10mM formic ammonium buffer (pH 3.0) (50:50) mobile phase at 0.20 ml/min at 37°C. The analytes were detected using a tandem mass spectrometer, equipped with an electrospray ion source (ESI). The instrument was used in multiple-reaction-monitoring (MRM) mode. The extraction yields from a 200 μl human plasma sample (containing 10 ng of each drugs) with the Oasis(®) MAX cartridge column were 93.3-102.5%. The detection limits were 0.01-6.5 ng/ml (S/N=3). Our developed method is very useful for the simultaneous determination of five oxicam (non-steroidal anti-inflammatory) drugs in human plasma by LC/MS/MS.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chromatography, Liquid; Forensic Toxicology; Humans; Meloxicam; Molecular Structure; Piroxicam; Tandem Mass Spectrometry; Thiazines; Thiazoles

Drug delivery via the nasal route is gaining increasing interest over the last two decades as an alternative to oral or parenteral drug administration. In the current study an approach for rapid identification of relevant features, screening and in vivo verification of potential therapeutic agents for nasal delivery was carried out using "analgesic agents" as an example. Four such drug candidates (rizatriptan, meloxicam, lornoxicam and nebivolol) were initially identified as potentially viable agents based on their therapeutic use and physicochemical characteristics. An in vitro screening was then carried out using the Calu-3 cell line model. Based on the in vitro screening results and the reported pharmacokinetic and the stability data, meloxicam was predicted to be the most promising drug candidate and was subsequently verified using an in vivo animal model. The in vivo results showed that nasal administration of meloxicam was comparable to its intravenous administration, with respect to plasma drug concentration and AUC(0-2h). In addition, nasal absorption of meloxicam was much more rapid with higher plasma drug concentration and AUC(0-2h) than that of oral administration. The current approach appears to be capable of developing "analgesic agents" suitable for nasal delivery. Further studies are needed to prove the clinical advantage of the specific selected agent, meloxicam, by nasal administration in patients.

Topics: Absorption; Administration, Intranasal; Administration, Oral; Analgesics; Animals; Area Under Curve; Benzopyrans; Cell Line; Drug Stability; Ethanolamines; Feasibility Studies; Humans; Hydrogen-Ion Concentration; Injections, Intravenous; Male; Meloxicam; Nasal Mucosa; Nebivolol; Permeability; Piroxicam; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Respiratory Mucosa; Thiazines; Thiazoles; Triazoles; Tryptamines

Transdermal patches of meloxicam (MX) and lornoxicam (LX) were aimed to be prepared in order to overcome their side effects by oral application. The strategy was formulation of optimized films to prepare transdermal patches by determination of physical properties and investigation of drug-excipient compatibility. As the next step, in vitro drug release, assesment of anti-inflammatory effect on Wistar Albino rats, ex vivo skin penetration and investigation of factors on drug release from transdermal patches were studied. Hydroxypropyl methylcellulose (HPMC) was concluded to be suitable polymer for formulation of MX and LX transdermal films indicating pharmaceutical quality required. MX and LX transdermal patches gave satisfactory results regarding to the edema inhibition in the assessment of anti-inflammatory effect. MX was found out to be more effective compared to LX on relieving of edema and swelling. These results were supported by data obtained from ex vivo penetration experiments of drug through rat skin. Indicative parameters like log P, molecular weight and solubility constraint on penetration rate of drugs also indicated good skin penetration. Transdermal patches of MX and LX can be suggested to be used especially for the immediate treatment of inflammated area since it displays anti-inflammatory effect, soon.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Calorimetry, Differential Scanning; Drug Delivery Systems; Edema; Hypromellose Derivatives; Meloxicam; Methylcellulose; Piroxicam; Rats; Rats, Wistar; Skin; Spectroscopy, Fourier Transform Infrared; Tensile Strength; Thiazines; Thiazoles

In this work it is explained, by the first time, the application of programs SQUAD and HYPNMR to refine equilibrium constant values through the fit of electrophoretic mobilities determined by capillary zone electrophoresis experiments, due to the mathematical isomorphism of UV-vis absorptivity coefficients, NMR chemical shifts and electrophoretic mobilities as a function of pH. Then, the pK(a) values of tenoxicam in H(2)O/DMSO 1:4 (v/v) have been obtained from (1)H NMR chemical shifts, as well as of oxicams in aqueous solution from electrophoretic mobilities determined by CZE, at 25 degrees C. These values are in very good agreement with those reported by spectrophotometric and potentiometric measurements.

Topics: Algorithms; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Spectroscopy; Meloxicam; Models, Chemical; Molecular Structure; Piroxicam; Software; Stereoisomerism; Thiazines; Thiazoles

Two sensitive and selective spectrofluorimetric and spectrophotometric stability-indicating methods have been developed for the determination of some non-steroidal anti-inflammatory oxicam derivatives namely lornoxicam (Lx), tenoxicam (Tx) and meloxicam (Mx) after their complete alkaline hydrolysis. The methods are based on derivatization of alkaline hydrolytic products with 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD-Cl). The products showed an absorption maximum at 460 nm for the three studied drugs and fluorescence emission peak at 535 nm in methanol. The color was stable for at least 48 h. The optimum conditions of the reaction were investigated and it was found that the reaction proceeds quantitatively at pH 8, after heating in a boiling water bath for 30 min. The methods were found to be linear in the ranges of 1-10 microg ml(-1) for Lx and Tx and 0.5-4.0 microg ml(-1) for Mx for spectrophotometric method, while 0.05-1.0 microg ml(-1) for Lx and Tx and 0.025-0.4 microg ml(-1) for Mx for the spectrofluorimetric method. The validity of the methods was assessed according to USP guidelines. Statistical analysis of the results revealed high accuracy and good precision. The suggested procedures could be used for the determination of the above mentioned drugs in pure and dosage forms as well as in the presence of their degradation products.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Buffers; Capsules; Drug Stability; Hydrogen-Ion Concentration; Indicators and Reagents; Meloxicam; Nitrobenzenes; Oxazoles; Pharmaceutical Solutions; Piroxicam; Powders; Reproducibility of Results; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Tablets; Thiazines; Thiazoles

Hypochlorous acid (HOCl) is an oxygen-derived species involved in physiological processes related to the defence of the organism that may cause adverse effects when its production is insufficiently controlled. In order to examine its reactivity with potential scavenging molecules from the non steroidal anti-inflammatory drugs (NSAIDs) family, a competition assay based on para-aminobenzoic acid (PABA) chlorination was developed. The original optimised in vitro fluorimetric procedure offered the possibility to determine rate constants (ks) for the reaction with HOCl in physiologically relevant conditions. The specificity of the system was improved by a liquid chromatography (LC) which allows the separation of the drugs and their oxidation products. After determination of the rate constant for PABA chlorination by HOCl (mean +/- SD in M(-1) s(-1): 4.3 +/- 0.3 x 10(3)), the applied mathematical model for a chemical competition permits to obtain linear curves from competition studies between several NSAIDs and PABA. Their slopes provided the following rate constants for the different studied drugs: tenoxicam: 4.0 +/- 0.7 x 10(3), piroxicam: 3.6 +/- 0.7 x 10(3), lornoxicam: 4.3 +/- 0.7 x 10(3), meloxicam: 1.7 +/- 0.3 x 10(4), nimesulide: 2.3 +/- 0.6 x 10(2). Meloxicam therefore reacted significantly faster than the other oxicams and nimesulide, which is the weakest scavenger of the studied series. The identification of some of the oxidation products by NMR or MS permitted to explore the reaction mechanism and to examine some aspects of the structure/activity relationships for the molecules of the same chemical family.

Topics: 4-Aminobenzoic Acid; Anti-Inflammatory Agents, Non-Steroidal; Binding, Competitive; Hypochlorous Acid; Kinetics; Linear Models; Meloxicam; Molecular Structure; Oxidation-Reduction; Piroxicam; Sulfonamides; Thiazines; Thiazoles

The thermal effects of non-steroidal anti-inflammatory drugs (NSAIDs) meloxicam, tenoxicam, piroxicam and lornoxicam have been studied in dipalmitoylphosphatidylcholine (DPPC) membrane bilayers using neutral and acidic environments (pH 2.5). The strength of the perturbing effect of the drugs is summarized to a lowering of the main phase transition temperature and a broadening of the phase transition temperature as well as broadening or abolishment of the pretransition of DPPC bilayers. The thermal profiles in the two environments were very similar. Among the NSAIDs studied meloxicam showed the least perturbing effect. The differential scanning calorimetry results (DSC) in combination with molecular modeling studies point out that NSAIDs are characterized by amphoteric interactions and are extended between the polar and hydrophobic segments of lipid bilayers. The effects of NSAIDs in membrane bilayers were also investigated using Raman spectroscopy. Meloxicam showed a gauche:trans profile similar to DPPC bilayers while the other NSAIDs increased significantly the gauche:trans ratio. In conclusion, both techniques show that in spite of the close structural similarity of the NSAIDs studied, meloxicam appears to have the lowest membrane perturbing effects probably attributed to its highest lipophilicity.

Topics: 1,2-Dipalmitoylphosphatidylcholine; Anti-Inflammatory Agents, Non-Steroidal; Calorimetry, Differential Scanning; Hydrogen-Ion Concentration; Lipid Bilayers; Meloxicam; Models, Molecular; Molecular Structure; Piroxicam; Spectrum Analysis, Raman; Structure-Activity Relationship; Temperature; Thiazines; Thiazoles

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used as analgesics. Although the results of clinical studies indicate considerable disparity in the analgesic efficacy of NSAIDs, the pre-clinical models generally used for the study of nociception do not allow a clear distinction to be made between the analgesic properties of agents belonging to this family. As clinical pain is characterized by hyperalgesia, we evaluated the effects of NSAIDs with similar chemical structures but different selectivities for cyclo-oxygenase (COX)-1 and COX-2 in a new behavioural model of central hyperalgesia in rats. We assessed the effects of lornoxicam, piroxicam, and meloxicam on the reduction of hindpaw nociceptive thresholds to thermal stimulation produced by a 10% formaldehyde (formalin) injection into rat tail. Each drug was administered intraperitoneally (i.p.) at its ED(50)for the anti-inflammatory effect (namely the inhibition of carrageenan-induced hindpaw oedema). At this dose (1.3 mg kg(-1), 1.0 mg kg(-1), and 5.8 mg kg(-1), respectively), lornoxicam, piroxicam, and meloxicam produced the same anti-inflammatory effect, did not modify thermal nociceptive thresholds, and significantly reduced the hyperalgesia. However, only lornoxicam was fully effective for prevention of hyperalgesia. Our results indicate a dissociation between the anti-inflammatory and the anti-hyperalgesic activity of NSAIDs, where the latter seems to be more evident after the block of both COX-1 and COX-2. Finally, they suggest that our experimental model of thermal hindpaw hyperalgesia can be effectively utilized to assess the ability of different drugs to reduce central sensitization, and thus hyperalgesia.

Topics: Analgesics, Non-Narcotic; Animals; Formaldehyde; Hindlimb; Hyperalgesia; Inflammation; Male; Meloxicam; Pain Threshold; Piroxicam; Rats; Rats, Sprague-Dawley; Tail; Thiazines; Thiazoles