mobic and Edema

Postoperative pain associated with removal of mandibular third molars has been documented from moderate to severe during the first 24 hours after surgery, with pain peaking between 6 and 8 hours when a conventional local anesthetic is used. Dental pain is largely inflammatory, and evidence-based medicine has shown that nonsteroidal anti-inflammatory drugs are the best analgesics for dental pain. The aim of this study was to compare the analgesic, anti-inflammatory and anti-trismus effect of a single dose of diclofenac and meloxicam after mandibular third molar extraction.. A total of 36 patients were randomized into two treatment groups, each with 18 patients, using a series of random numbers: Group A, was administered 100 mg of diclofenac; and Group B, 15 mg of meloxicam. Drugs were administered orally 1 hour prior to surgery. We evaluated pain intensity, analgesic consumption, swelling, as well as trismus.. The results of this study showed that patients receiving 15 mg of meloxicam had less postoperative pain (P=0.04) and better aperture than those receiving 100 mg of diclofenac (P=0.03). The meloxicam group presented less swelling than diclofenac group; however, significant statistical differences were not observed.. Data of this double-blind, randomized, parallel-group clinical trial demonstrated that patients receiving 15 mg of preoperative meloxicam had a better postoperative analgesia and anti-trismus effect compared with who were given 100 mg of diclofenac after third molar extractions.

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Double-Blind Method; Edema; Female; Humans; Male; Meloxicam; Molar, Third; Pain, Postoperative; Thiazines; Thiazoles; Tooth Extraction; Trismus; Young Adult

To compare the pre-emptive analgesic effectiveness of 15 mg of meloxicam and 50 mg of tramadol after mandibular third molar surgery.. This pilot study was a double-blind, randomized, parallel-group clinical trial. The patients were randomized into 2 treatment groups, each with 15 patients, by use of a series of random numbers: group A was administered 15 mg of meloxicam intramuscularly (IM) 50 minutes before the surgery and group B was given 50 mg of tramadol IM 50 minutes before the surgery. We evaluated pain intensity, analgesic consumption, swelling, and trismus.. The group receiving 15 mg of meloxicam IM showed differences in pain intensity evaluated by the area under the curve of the visual analog scale and total analgesic consumption when compared with the group receiving 50 mg of tramadol IM.. The patients receiving 15 mg of preoperative meloxicam had less pain intensity and total analgesic consumption than those receiving 50 mg of preoperative tramadol.

Topics: Adolescent; Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Edema; Female; Humans; Injections, Intramuscular; Ketorolac; Male; Mandible; Meloxicam; Molar, Third; Pain Measurement; Pain, Postoperative; Pilot Projects; Postoperative Complications; Premedication; Thiazines; Thiazoles; Time Factors; Tooth Extraction; Tooth, Impacted; Tramadol; Trismus; Young Adult

Nonsteroidal anti-inflammatory medication is used to reduce prostate edema and urinary symptoms following prostate brachytherapy. We hypothesized that a cyclooxygenase-2 (COX-2) inhibitor regimen started 1 week prior to seed implant might diminish the inflammatory response, thus reducing edema, retention rates, and symptom severity.. From March 2004 to February 2008, 316 men consented to an institutional review board-approved randomized study of a 4-week course of meloxicam, 7.5 mg orally twice per day, starting either on the day of implant or 1 week prior to implant. Brachytherapy was performed using iodine-125 seeds and was preplanned and performed under transrectal ultrasound (TRUS) and fluoroscopic guidance. Prostate volume obtained by MR imaging at 1 month was compared to baseline prostate volume obtained by TRUS planimetry and expressed as an edema factor. The trial endpoints were prostate edema at 1 month, International Prostate Symptom Score (IPSS) questionnaire results at 1 and 3 months, and any need for catheterization.. Results for 300 men were analyzed. Median age was 61 (range, 45-79 years), and median TRUS prostate volume was 35.7 cc (range, 18.1-69.5 cc). Median IPSS at baseline was 5 (range, 0-24) and was 15 at 1 month, 16 at 3 months, and 10 at 6 months. Catheterization was required for 7% of patients (6.2% day 0 arm vs. 7.9% day -7 arm; p = 0.65). The median edema factor at 1 month was 1.02 (range, 0.73-1.7). 1.01 day 0 arm vs. 1.05 day -7 arm. Baseline prostate volume remained the primary predictor of postimplant urinary retention.. Starting meloxicam 1 week prior to brachytherapy compared to starting immediately after the procedure did not reduce 1-month edema, improve IPSSs at 1 or 3 months, or reduce the need for catheterization.

Topics: Administration, Oral; Aged; Anti-Inflammatory Agents, Non-Steroidal; Brachytherapy; Cyclooxygenase 2 Inhibitors; Drug Administration Schedule; Edema; Humans; Iodine Radioisotopes; Male; Meloxicam; Middle Aged; Ontario; Prostatic Diseases; Thiazines; Thiazoles; Urinary Retention

This study compared the efficacy of nimesulide and meloxicam in the control of pain, swelling and trismus, following the extraction of impacted inferior third molars. Twenty patients with two impacted inferior third molars, in similar positions, were selected. The patients were designated randomly to the meloxicam group (MEL: 7.5mg twice a day for 5 days) or the nimesulide group (NIM: 100mg for 5 days). Following the extractions, swelling was more pronounced in the MEL group than in the NIM group (P0.05). At the 72-h evaluation, reduction was significantly larger in mouth opening in the MEL group compared with the NIM group (P<0.05). In conclusion, pain control was similar in both treatment groups. NIM was more effective than MEL in the control of swelling and trismus following the extraction of impacted lower third molars.

Topics: Cross-Over Studies; Cyclooxygenase Inhibitors; Edema; Female; Humans; Male; Meloxicam; Molar, Third; Pain Measurement; Pain, Postoperative; Sulfonamides; Thiazines; Thiazoles; Tooth Extraction; Tooth, Impacted; Trismus; Young Adult

Fifty patients were scheduled to undergo removal of symmetrically positioned lower third molars in two separate appointments. Meloxicam 7.5 or 15 mg was once daily administered in a double-blind, randomized and crossover manner after the surgery for 4 days. Objective and subjective parameters were recorded for comparison of postoperative courses. Patients treated with 7.5mg meloxicam who underwent osteotomy reported higher pain scores at 1.5, 3, 4, 10, 12 and 16 h (P<0.05) and ingested a greater amount of rescue analgesic medication (P<0.05) than those who did not require osteotomy. A higher percentage of patients who underwent osteotomy medicated with 7.5mg meloxicam needed rescue medication as compared to those who did not require osteotomy (P<0.05). There was a similar mouth opening at suture removal compared with preoperative values for both doses (P>0.05). There were no significant differences concerning swelling observed on the 2nd or 7th postoperative days in comparison with baseline (P>0.05) between the two doses. Pain, trismus and swelling after lower third molar removal not requiring osteotomy can be successfully controlled by a dose regimen of 7.5mg meloxicam once daily. For more aggressive extractions 15 mg meloxicam is advisable.

Topics: Administration, Oral; Adult; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Edema; Female; Humans; Male; Meloxicam; Molar, Third; Osteotomy; Pain, Postoperative; Range of Motion, Articular; Statistics, Nonparametric; Thiazines; Thiazoles; Tooth Extraction; Tooth, Impacted; Trismus

Minocycline is a semi-synthetic antimicrobial agent with claimed anti-inflammatory properties reported from different experimental models. This study was aimed to evaluate the anti-inflammatory effects of minocycline, compared to the actions of two common anti-inflammatory agents, on lipopolysaccharide (LPS)-induced paw oedema through some clinical, histopathological, haematological and molecular analyses. Forty-eight rats were divided into eight groups (n = 6). In control group (Ctrl), each animal was injected with normal saline into its sub-plantar region of hind paw. In groups 2-7, hind paw oedema was induced by injection of LPS. One hour before injections, groups 1 (Ctrl) and 2 (LPS) were treated orally with distilled water, 3 and 4 with methylprednisolone (Pred) and meloxicam (Melo) and 5-7 with minocycline in doses of 50, 150 and 450 mg/kg (M50, M150 and M450, respectively). The 8th group (MC) was given minocycline (150 mg/kg) orally and normal saline was injected into sub-plantar region. Paw swelling and body temperature were assessed at 0, 2, 4, 6 and 24 h post-injections. At 24 h, samples of blood and liver, kidney, spleen and hind paw tissues were taken for haematological and histopathological examinations. Some samples of the paw were also obtained for molecular analysis of some inflammatory-related cytokines at mRNA level. Paw swelling and body temperature increased in all LPS-injected groups 2 h post-injection. In LPS group, they remained significantly increased up to 24 h; however, these parameters decreased to normal in Pred, Melo and all minocycline groups. The histological findings showed mild-to-moderate signs of inflammation in tissue samples of groups 2-6, but not in group M450. Additionally, gene expression of pro-inflammatory cytokines (IL-1β and IL-6) increased significantly in LPS group compared to other groups. In conclusion, this study supports the role of minocycline as an anti-inflammatory agent with effects comparable to those of meloxicam and methylprednisolone.

Topics: Animals; Anti-Inflammatory Agents; Cytokines; Edema; Inflammation; Lipopolysaccharides; Meloxicam; Methylprednisolone; Minocycline; Rats; Saline Solution

Alzheimer's disease (AD) is a neurodegenerative disease majorly affecting old age populations. Various factors that affect the progression of the disease include, amyloid plaque formation, neurofibrillary tangles, inflammation, oxidative stress, etc. Herein we report of a new series of substituted (2-aminothiazol-5-yl)(imidazo[1,2-a]pyridin-3-yl)methanones. The designed compounds were synthesized and characterized by spectral data. In vivo anti-inflammatory activity was carried out for screening of anti-inflammatory potential of synthesized compounds. All the compounds were tested for acute inflammatory activity by using carrageenan induced acute inflammation model. Compounds 10b, 10c, and 10o had shown promising acute anti-inflammatory activity and they were further tested for formalin induced chronic inflammation model. Compound 10c showed both acute and chronic anti-inflammatory activity. Compound 10c also showed promising results in AlCl

Topics: Aluminum Chloride; Alzheimer Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Edema; Female; Formaldehyde; Imidazoles; Inflammation; Male; Molecular Structure; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship

Fast dissolution of nonsteroidal anti-inflammatory drugs (NSAIDs) is a prerequisite from patient perspective. However, most NSAIDs are slowly dissolving acidic compounds. Caffeine, a commonly used analgesic adjuvant with NSAIDs showed high potential as eutectic co-former for acidic compounds. The study investigated eutectic forming potential of caffeine with meloxicam, aceclofenac and flurbiprofen. Each drug was co-ground with caffeine in various ratios and the products were characterized by thermal analysis to determine the optimum eutectic composition from phase diagram and Tamman's triangle. The optimum systems were subjected to X-ray powder diffraction (XRPD), Fourier-transform infrared (FTIR) and dissolution studies. Co-ground systems at dose ratio were also assessed for drug dissolution and anti-inflammatory effect using carrageenan induced rat paw edema method. Eutexia was confirmed by thermal analysis with the optimum composition being 1:1, 1:1 and 1:2 (NSAID: caffeine) for aceclofenac, flurbiprofen and meloxicam, respectively. Eutexia did not alter FTIR spectra with minor changes being recorded in XRPD patterns. The eutectic systems underwent fast liberation of drugs with fast dissolution being retained even at dose ratios. Dissolution enhancement was associated with enhanced anti-inflammatory response. The study introduced caffeine as eutectic forming analgesic for fixed dose combination with NSAIDs to enhance drug dissolution and anti-inflammatory effect.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Caffeine; Carrageenan; Diclofenac; Drug Liberation; Edema; Flurbiprofen; Male; Meloxicam; Powder Diffraction; Rats, Wistar; Spectroscopy, Fourier Transform Infrared; Transition Temperature; X-Ray Diffraction

Rutin, naturally occurring flavonoid, has reported to cover interesting multiple pharmacological properties. This study evaluated rutin or/and meloxicam effects in paw inflammation induced by formalin in mice. Mice were divided into four groups: I-Formalin group, II-Rutin 60 mg/kg (p.o.), III-Meloxicam 10 mg/kg (p.o.), plus IV-Combined rutin and meloxicam. Therapies were administered once a day for 7 days. The curative effects were assessed on inflammatory, oxidative stress, and apoptosis. Both rutin and/or meloxicam induced marked improvement in paw licking time on the 1st day and by combined treatment only on the 3rd day as well reduction in paw edema% on the 3rd day. Moreover, noticeable progress in liver malondialdehyde content, superoxide dismutase, and sorbitol dehydrogenase activities as well decline in paw interleukin-1β level and extent of apoptosis. The results spot light on the good influence of combined rutin and meloxicam in formalin-induced mice paw inflammation to a better extent than either rutin or meloxicam lonely.

Topics: Acute Pain; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Apoptosis; Behavior, Animal; Cellulitis; Connective Tissue; Disease Models, Animal; Drug Therapy, Combination; Edema; L-Iditol 2-Dehydrogenase; Liver; Male; Meloxicam; Mice; Organ Size; Oxidative Stress; Random Allocation; Rutin; Superoxide Dismutase; Thiazines; Thiazoles

Osteoarthritis (OA) is a common progressive joint disease in dogs and cats. The goal of OA treatment is to reduce inflammation, minimize pain, and maintain joint function. Currently, non-steroidal anti-inflammatory drugs (e.g., meloxicam) are the cornerstone of treatment for OA pain, but side effects with long-term use pose important challenges to veterinary practitioners when dealing with OA pain. Palmitoylethanolamide (PEA) is a naturally-occurring fatty acid amide, locally produced on demand by tissues in response to stress. PEA endogenous levels change during inflammatory and painful conditions, including OA, i.e., they are typically increased during acute conditions and decreased in chronic inflammation. Systemic treatment with PEA has anti-inflammatory and pain-relieving effects in several disorders, yet data are lacking in OA. Here we tested a new composite, i.e., PEA co-ultramicronized with the natural antioxidant quercetin (PEA-Q), administered orally in two different rat models of inflammatory and OA pain, namely carrageenan paw oedema and sodium monoiodoacetate (MIA)-induced OA. Oral treatment with meloxicam was used as benchmark.. PEA-Q decreased inflammatory and hyperalgesic responses induced by carrageenan injection, as shown by: (i) paw oedema reduction, (ii) decreased severity in histological inflammatory score, (iii) reduced activity of myeloperoxidase, i.e., a marker of inflammatory cell infiltration, and (iv) decreased thermal hyperalgesia. Overall PEA-Q showed superior effects compared to meloxicam. In MIA-treated animals, PEA-Q exerted the following effects: (i) reduced mechanical allodynia and improved locomotor function, (ii) protected cartilage against MIA-induced histological damage, and (iii) counteracted the increased serum concentration of tumor necrosis factor alpha, interleukin 1 beta, metalloproteases 1, 3, 9 and nerve growth factor. The magnitude of these effects was comparable to, or even greater than, those of meloxicam.. The present findings shed new light on some of the inflammatory and nociceptive pathways and mediators targeted by PEA-Q and confirm its anti-inflammatory and pain-relieving effects in rodent OA pain models. The translatability of these observations to canine and feline OA pain is currently under investigation.

Topics: Administration, Oral; Amides; Animals; Anti-Inflammatory Agents; Carrageenan; Drug Combinations; Edema; Ethanolamines; Hyperalgesia; Inflammation; Male; Meloxicam; Osteoarthritis; Pain; Palmitic Acids; Quercetin; Rats, Sprague-Dawley; Thiazines; Thiazoles

The present study was designed to examine the antinociceptive and anti-inflammatory effects of 7-chloro-4-phenylsulfonyl quinoline (PSOQ). Mice were orally (p.o) pretreated with PSOQ (0.01-10 mg/kg), meloxicam (10 mg/kg), 30 min prior to the acetic acid, hot-plate and open field tests. PSOQ reduced abdominal writhing induced by acetic acid, while meloxicam presented no effect. The latency time in the hot-plate test and locomotor/exploratory activities in the open field test were not altered by treatments. In order to evaluate the gastric tolerability after oral administration of PSOQ or meloxicam (10 mg/kg), mice were fasted for 18 h prior to drug exposure. Four hours later, the development of lesions was assessed. PSOQ and meloxicam did not induce ulcer at the dose and time evaluated. Indeed, anti-inflammatory and anti-edematogenic properties of PSOQ were investigated. For this, animals were pretreated with PSOQ (0.01-50 mg/kg; p.o.), meloxicam (50 mg/kg; p.o.), 30 min prior to croton oil application. PSOQ and meloxicam (50 mg/kg) diminished the edema formation and myeloperoxidase activity induced by croton oil in the ear tissue. Taken together these data demonstrated that PSOQ exerts acute anti-inflammatory and antinociceptive actions, suggesting that it may represent an alternative in the development of future new therapeutic strategies.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Croton Oil; Edema; Hot Temperature; Humans; Male; Meloxicam; Mice; Nociception; Pain; Quinolines; Stomach Ulcer; Thiazines; Thiazoles

In this study, we evaluated the edema and hyperalgesic response induced by BpirMP, a P-I class metalloproteinase isolated from Bothrops pirajai snake venom. The animals were injected with the metalloproteinase or sterile PBS (control group) and evaluated for 1, 2, 3, 4, 5, 6 and 24h. The intraplantar injection of BpirMP (5-50μg/paw) induced a dose- and time-dependent response. BpirMP (50μg) induced paw edema in rats rapidly, with peak response two hours after injection of the toxin. Also, BpirMP injection caused a significant reduction in the nociceptive threshold of the animals tested, with peak response three hours after injection of the toxin. The inflammatory mediators involved in these responses were assayed by pretreatment of animals with synthesis inhibitors or receptor antagonists. Peak responses were significantly reduced by pretreatment of animals with pyrilamine, a histamine receptor antagonist, sodium cromoglycate, a mast cell degranulation inhibitor and valeryl salicylate and meloxicam, cyclooxygenase inhibitors. The analysis of the peritoneal cavity exudate revealed an acute inflammatory response with recruitment of leukocytes, increased levels of total proteins, nitric oxide and the cytokines IL-6, TNF-α and IL-10. In conclusion, our results demonstrated that BpirMP induces inflammation mediated by mast cell degranulation, histamine, prostaglandins and cytokine production.

Topics: Animals; Bothrops; Cell Degranulation; Cromolyn Sodium; Crotalid Venoms; Cyclooxygenase Inhibitors; Edema; Female; Histamine H1 Antagonists; Hyperalgesia; Inflammation; Interleukin-10; Interleukin-6; Leukocytes; Male; Mast Cells; Meloxicam; Metalloproteases; Mice; Mice, Inbred BALB C; Nitric Oxide; Nociception; Pyrilamine; Rats; Rats, Wistar; Salicylates; Thiazines; Thiazoles; Tumor Necrosis Factor-alpha; Viper Venoms

The development of new treatments for inflammation and pain continues to be of high interest, since long-acting effect is critical for patients. The present study investigated whether the polymeric nanocapsules, a drug delivery system, have pharmacological effect on acute nociceptive and inflammatory models in mice.. Swiss mice (20-25 g) were previously pre-treated with meloxicam-loaded nanocapsules (M-NC) or free meloxicam (M-F) or suspension without drug (B-NC), at a dose of 5 mg/kg (per oral) at different times (0.5-120 h). Antinociceptive and antiedematogenic effects were evaluated by chemical (acetic acid-induced abdominal writhing, nociception and paw edema induced by formalin and glutamate, croton oil-induced ear edema) and thermal (tail immersion and hot-plate) tests.. M-NC reduced the licking time- and paw edema-induced by glutamate and formalin, while M-F did not have an effect. In the acetic acid-induced abdominal writhing and croton oil-induced ear edema, analysis of time-course revealed that M-NC showed a response more prolonged than M-F. In the hot-plate test, a thermal test, the time-course analysis indicated a similar increase in the latency response to thermal stimuli of M-NC and M-F, while in the tail-immersion test M-F had an effect at 0.5 h and M-NC at 24 h.. Polymeric nanoparticles had antinociceptive, anti-inflammatory and antiedematogenic effects in the formalin and glutamate tests, and prolonged the effect in acetic acid and croton oil tests, but not in thermal tests, supporting the idea that the inflammatory process in tissues facilitates the vectoring of polymeric nanoparticles.

Topics: Acute Pain; Analgesics; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Croton Oil; Ear; Edema; Extremities; Formaldehyde; Glutamic Acid; Male; Meloxicam; Mice; Nanocapsules; Nociception; Pain Measurement; Thiazines; Thiazoles

The aim of this study was to synthesize three nitro substituted chalcones and to evaluate their anti-inflammatory activity in the model of carrageenan induced edema in rats. The nitro chalcone were prepared by aldol condensation using of mechanical agitation and environmentally friendly solvents with 72-73% yields in approximately 2h. The three structures were evaluated on biological activity at dose of 200mg/kg and they showed anti-inflammatory protective effect by both oral and intraperitoneal administration, this effect was time dependent.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Area Under Curve; Chalcone; Disease Models, Animal; Edema; Rats; ROC Curve

The main objective of the current investigation was to develop nanostructured lipid carriers (NLC) based gel for the enhancement of transdermal absorption of meloxicam (MLX) to achieve local as well as systemic drug action without concurrent gastrointestinal toxicity.. NLC gel containing MLX was prepared and characterized for particle size, polydispersity, zeta potential, pH, rheology, entrapment efficiency, occlusion factor, and thermal behavior. In vitro drug release, in vitro skin permeation and deposition studies were carried out using Franz diffusion cells. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) of MLX-NLC gel treated stratum corneum (SC) were undertaken to get an insight into the skin permeation enhancement mechanism of MLX-NLC gel. Toxicity potential of the developed gel formulation was assessed by in vitro hemolysis and histopathological examinations. The rat paw edema test was performed to evaluate the anti-inflammatory activity of MLX-NLC gel.. MLX-NLC gel demonstrated sustained release and enhanced the skin permeation and deposition of meloxicam especially into the dermis in comparison to meloxicam gel (control). MLX-NLC had an impact on the barrier properties of the skin and acted via protein and lipid modifications in the stratum corneum. MLX-NLC gel turned out to be hemocompatible, non-irritant, and non toxic with significant anti-inflammatory activity.. The results suggest that NLC gel could be a promising carrier for the transdermal delivery of meloxicam.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Delayed-Action Preparations; Drug Carriers; Edema; Gels; Hydrogen-Ion Concentration; Meloxicam; Nanostructures; Particle Size; Rats; Rheology; Skin Absorption; Surface Properties; Thiazines; Thiazoles

The aim of the present investigation was to develop a nanoemulsion (NE) gel formulation for the transdermal delivery of meloxicam (MLX) in order to ensure maximum controlled and sustained drug release capacity.. The MLX containing NE gel was prepared and characterized for particle size, zeta potential, pH, rheology, in vitro drug release, in vitro skin permeation, and in vitro hemolysis. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) of MLX-NE gel treated rat skin was performed to investigate the skin permeation mechanism of meloxicam from NE gel. Skin permeation potential of the developed gel formulation was assessed using confocal laser scanning microscopy (CLSM). The in vivo toxicity of MLX-NE gel was assessed by histopathological examination in rat. The rat paw edema test was performed to evaluate the anti-inflammatory activity of MLX-NE gel.. Percutaneous absorption studies demonstrated a higher permeation of meloxicam from NE gel, than the drug solution. FTIR and DSC studies supported stratum corneum lipid extraction as a possible penetration enhancer mechanism for MLX-NE gel. CLSM studies confirmed the permeation of the NE gel formulation to the deeper layers of the skin (up to 130 μm). MLX-NE gel turned out to be non-irritant, biocompatible, and provided maximum inhibition of paw edema in rats over 24 h in contrast to MLX solution.. The nanoemulsion gel formulation may hold promise as an effective alternative for the transdermal delivery of meloxicam.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Chemical Phenomena; Disease Models, Animal; Edema; Female; Gels; Hemolysis; Humans; Male; Meloxicam; Nanotechnology; Particle Size; Rats; Rheology; Skin; Skin Absorption; Surface Properties; Thiazines; Thiazoles

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Edema; Humans; Meloxicam; Molar, Third; Pain, Postoperative; Sulfonamides; Thiazines; Thiazoles; Tooth Extraction; Tooth, Impacted; Trismus

The potential of positively charged polymeric nanoparticles in improving therapeutic efficacy of meloxicam (MLX), a poorly water-soluble anti-inflammatory agent was evaluated. MLX loaded positively charged nanoparticles were prepared by using poly-epsilon-caprolactone (PCL) as a biodegradable polymer and didodecyldimethylammonium bromide (DDAB) as a cationic surfactant. The MLX nanoparticles were characterized for particle size and encapsulation efficiency. MLX loaded PCL nanoparticles and MLX suspension were evaluated for their in vivo anti-inflammatory activity and ulcerogenic potential. MLX loaded PCL nanoparticles had particle sizes of approximately 300 nm and the encapsulation efficiency of MLX was approximately 90%. The polymeric nanoparticles significantly improved the anti-inflammatory activity of MLX (P< 0.01) as compared to that of MLX suspension. The higher anti-inflammatory effect was maintained for a longer duration (6 h). The polymeric nanoparticles also resulted in less ulcerogenicity as compared to that of MLX suspension.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Caproates; Carrageenan; Edema; Foot; Freeze Drying; Lactones; Male; Meloxicam; Nanoparticles; Particle Size; Polymers; Quaternary Ammonium Compounds; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Surface-Active Agents; Suspensions; Thiazines; Thiazoles

A monolithic drug-in-adhesive (MDIA) type patch containing meloxicam (MX) was designed with an acrylic adhesive, a solubility modulator increasing MX solubility, and enhancers. MDIA patches having one adhesive layer between the backing and the release liner give high productivity and improve patient compliance. The biggest problem to prepare MDIA patch including MX was poor solubility of MX. In this research, solubility modulators to increase solubility of MX and acrylic adhesives and skin permeation enhancers were investigated through solubility tests, in vitro skin permeation tests, and stability tests. Consequently, the composition of sodium methoxide (SM), an acrylic adhesive containing poly(vinyl pyrrolidone) blocks (MAS683), polyoxyethylene cetylether (BC-2), and diisopropanolamine (DIPA) made it possible for MX to be contained in an adhesive layer at a concentration of as much as 15 wt% without MX crystal and with high skin permeation over 400 microG/cm(2). Finally, the patch formulation containing MX (MX-patch) selected through our in vitro study was characterized by in vivo using an animal study to acquire pharmacokinetic (PK) parameters and to confirm the anti-inflammatory efficacy of MX-patch. In the animal study, MX-patch was compared with a commercially available piroxicam patch (PX-patch). The amount of MX delivered from MX-patch to the skin surface was believed to be higher than the amount of MX diffused from the skin tissue to circulatory system because the plasma concentration of MX continuously increased up to 32 h, the end time of PK study, although the patch samples were detached at 24 h. PX-patch produced a C(max) at 8 h. MX-patch showed better significant efficacy than PX-patch in adjuvant arthritis model.

Topics: Acrylic Resins; Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Carrageenan; Chemistry, Pharmaceutical; Diffusion; Disease Models, Animal; Dosage Forms; Drug Compounding; Drug Stability; Edema; Excipients; Freund's Adjuvant; Meloxicam; Mice; Mice, Hairless; Mycobacterium; Osteoarthritis; Permeability; Piroxicam; Povidone; Rats; Rats, Sprague-Dawley; Skin; Skin Absorption; Solubility; Technology, Pharmaceutical; Thiazines; Thiazoles; Tissue Adhesives

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

5-Aryl-2,2-dialkyl-4-phenyl-3(2H)furanone derivatives were studied as a novel class of selective cyclooxygenase-2 inhibitors with regard to synthesis, in vitro SAR, antiinflammatory activities, pharmacokinetic considerations, and gastric safety. 1f, a representative compound for methyl sulfone derivatives, showed a COX-2 IC(50) comparable to that of rofecoxib. In case of 20b, a representative compound for sulfonamide derivatives, a potent antiinflammatory ED(50) of 0.1 mg kg(-1) day(-1) was observed against adjuvant-induced arthritis by a preventive model, positioning 20b as one of the most potent COX-2 inhibitors ever reported. Furthermore, 20b showed strong analgesic activity as indicated by its ED(50) of 0.25 mg/kg against carrageenan-induced thermal hyperalgesia in the Sprague-Dawley rat. 3(2H)Furanone derivatives showed due gastric safety profiles as selective COX-2 inhibitors upon 7-day repeat dosing. A highly potent COX-2 inhibitor of the 3(2H)furanone scaffold could be considered suitable for a future generation COX-2 selective arthritis medication with improved safety profiles.

Topics: Adult; Animals; Arthritis, Experimental; Carrageenan; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Edema; Furans; Humans; In Vitro Techniques; Isoenzymes; Macrophages, Peritoneal; Male; Membrane Proteins; Mice; Models, Molecular; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Structure-Activity Relationship

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Cyclodextrins; Edema; Intestinal Mucosa; Male; Meloxicam; Rats; Rats, Wistar; Stomach Ulcer; Thiazines; Thiazoles

Adjuvant arthritic rats are known to be more susceptible to gastric damage induced by non-steroidal anti-inflammatory drugs (NSAIDs) than are normal rats. We compared the relative gastric safety profile of etodolac with those of meloxicam, diclofenac sodium and indometacin in adjuvant arthritic rats and normal rats or mice. As a measure of the safety profiles of NSAIDs, we used the safety index, the ratio of the dose that elicits gastric mucosal lesions to the effective dose as an anti-inflammatory or analgesic compound. The anti-inflammatory or analgesic effects of NSAIDs were assessed by paw swelling in adjuvant arthritic rats, and either carrageenin-induced paw edema or brewer's yeast-induced hyperalgesia, as well as acetic acid-induced writhing, in normal rats or mice. In addition, we also investigated the effects of these NSAIDs on human COX-1 and COX-2 activity. Etodolac and other NSAIDs inhibited paw swelling and caused gastric mucosal lesions in adjuvant arthritic rats in a dose-dependent manner. Etodolac showed the highest UD(50) value and safety index among these NSAIDs in arthritic rats. In normal rats, etodolac also showed the highest UD(50) value and safety index, except when its effects were assessed by acetic acid-induced writhing. Etodolac and meloxicam showed selectivity for human COX-2 over COX-1. In contrast, diclofenac sodium and indometacin were selective for COX-1. These results suggest that etodolac, a COX-2 selective NSAID, has anti-inflammatory effects with a better safety profile for the stomach than do non-selective NSAIDs, including diclofenac sodium and indometacin, in adjuvant arthritic as well as normal rats.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Cyclooxygenase Inhibitors; Diclofenac; Edema; Etodolac; Gastric Mucosa; Indomethacin; Male; Meloxicam; Mice; Peptic Ulcer; Rats; Species Specificity; Thiazines; Thiazoles

A series of 2-benzyl-4-sulfonyl-4H-isoquinoline-1,3-diones was prepared. Members of this series are potent and selective inhibitors of cyclooxygenase-2 (COX-2) in both microsomal and cellular assays. Two representatives demonstrated activity in the carrageenan-induced paw edema model in rats upon oral administration.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Edema; Isoenzymes; Isoquinolines; Kinetics; Membrane Proteins; Microsomes; Molecular Structure; Prostaglandin-Endoperoxide Synthases; Rats; Structure-Activity Relationship

Meloxicam (Mel) is a new non-steroidal anti-inflammatory drug (NSAID) which was selected with regard to its remarkable efficacy in adjuvant arthritis of the rat. Similar to the situation in man, three main metabolites were identified in rat urine which are rapidly excreted since they are not detectable in blood, where only the parent compound was found. The latter is practically not eliminated in urine. Since it has been proposed that the nephrotoxicity of NSAIDs is due to inhibition of prostaglandin E2 (PG) biosynthesis, the aim of the study was to determine whether the metabolites can contribute to the known effects of the parent compound in this pathway. For this purpose, PG-biosynthesis was measured in vitro using a radiochemical technique with an enzyme preparation from bull seminal vesicles. In an in vivo assay the effect of the compounds against kaolin-induced oedema in the rat hind paw was determined. In the test systems described, the efficacy of Mel has been demonstrated. In contrast to this finding, the metabolites in relevant doses showed neither in vitro nor in vivo effects. From the results it can be concluded that the metabolites do not change renal blood flow and therefore have no capability for nephrotoxicity. These findings are in accordance with the observations in the rat kidney during subacute and chronic toxicity studies, where no nephrotoxic effects could be detected after therapeutic doses.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Edema; Exudates and Transudates; Kaolin; Male; Meloxicam; Prostaglandins; Rats; Thiazines; Thiazoles