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Sample records for piroxicam

  1. Piroxicam

    Science.gov (United States)

    Piroxicam is also sometimes used to treat gouty arthritis (attacks of severe joint pain and swelling caused by a build-up of certain substances in the joints) and ankylosing spondylitis (arthritis that ...

  2. Piroxicam overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002534.htm Piroxicam overdose To use the sharing features on this page, please enable JavaScript. Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) used ...

  3. Piroxicam derivatives THz classification

    Science.gov (United States)

    Sterczewski, Lukasz A.; Grzelczak, Michal P.; Nowak, Kacper; Szlachetko, Bogusław; Plinska, Stanislawa; Szczesniak-Siega, Berenika; Malinka, Wieslaw; Plinski, Edward F.

    2016-02-01

    In this paper we report a new approach to linking the terahertz spectral shapes of drug candidates having a similar molecular structure to their chemical and physical parameters. We examined 27 newly-synthesized derivatives of a well-known nonsteroidal anti-inflammatory drug Piroxicam used for treatment of inflammatory arthritis and chemoprevention of colon cancer. The testing was carried out by means of terahertz pulsed spectroscopy (TPS). Using chemometric techniques we evaluated their spectral similarity in the terahertz range and attempted to link the position on the principal component analysis (PCA) score map to the similarity of molecular descriptors. A simplified spectral model preserved 75% and 85.1% of the variance in 2 and 3 dimensions respectively, compared to the input 1137. We have found that in 85% of the investigated samples a similarity of the physical and chemical parameters corresponds to a similarity in the terahertz spectra. The effects of data preprocessing on the generated maps are also discussed. The technique presented can support the choice of the most promising drug candidates for clinical trials in pharmacological research.

  4. Piroxicam-β-cyclodextrin: a GI safer piroxicam.

    Science.gov (United States)

    Scarpignato, C

    2013-01-01

    more rapid onset of action after oral administration and improved GI tolerability because of minimization of the drug gastric effects. One such drug, piroxicam-β-cyclodextrin (PBC), has been used in Europe for 25 years. Preclinical and clinical pharmacology of PBC do show that the β-cyclodextrin inclusion complex of piroxicam is better tolerated from the upper GI tract than free piroxicam, while retaining all the analgesic and anti-inflammatory properties of the parent compound. In addition, the drug is endowed with a quick absorption rate, which translates into a faster onset of analgesic activity, an effect confirmed in several clinical studies. An analysis of the available trials show that PBC has a GI safety profile, which is better than that displayed by uncomplexed piroxicam. Being an inclusion complex of piroxicam, whose CV safety has been pointed out by several observational studies, PBC should be viewed as a CV safe anti-inflmmatory compound and a GI safer alternative to piroxicam. As a consequence, it should be considered as a useful addition to our therapeutic armamentarium.

  5. Crystal modifications and dissolution rate of piroxicam.

    Science.gov (United States)

    Lyn, Lim Yee; Sze, Huan Wen; Rajendran, Adhiyaman; Adinarayana, Gorajana; Dua, Kamal; Garg, Sanjay

    2011-12-01

    Piroxicam is a nonsteroidal anti-inflammatory drug with low aqueous solubility which exhibits polymorphism. The present study was carried out to develop polymorphs of piroxicam with enhanced solubility and dissolution rate by the crystal modification technique using different solvent mixtures prepared with PEG 4000 and PVP K30. Physicochemical characteristics of the modified crystal forms of piroxicam were investigated by X-ray powder diffractometry, FT-IR spectrophotometry and differential scanning calorimetry. Dissolution and solubility profiles of each modified crystal form were studied and compared with pure piroxicam. Solvent evaporation method (method I) produced both needle and cubic shaped crystals. Slow crystallization from ethanol with addition of PEG 4000 or PVP K30 at room temperature (method II) produced cubic crystal forms. Needle forms produced by method I improved dissolution but not solubility. Cubic crystals produced by method I had a dissolution profile similar to that of untreated piroxicam but showed better solubility than untreated piroxicam. Cubic shaped crystals produced by method II showed improved dissolution, without a significant change in solubility. Based on the XRPD results, modified piroxicam crystals obtained by method I from acetone/benzene were cube shaped, which correlates well with the FTIR spectrum; modified needle forms obtained from ethanol/methanol and ethanol/acetone showed a slight shift of FTIR peak that may be attributed to differences in the internal structure or conformation.

  6. Transdermal Delivery of Piroxicam by Surfactant Mediated Electroporation

    Institute of Scientific and Technical Information of China (English)

    ZAN Jia; JIANG Guoqiang; LIN Ying; TAN Fengping; DING Fuxin

    2005-01-01

    A lipophilic, nonsteroidal antiinflammation drug, piroxicam, was administered by skin electroporation using short, high-voltage pulses. The transdermal delivery of piroxicam during the electroporation was buffered due to the higher partition in skin lipids than in aqueous environments, which is called entrapment. Entrapment is the main resistance to transdermal delivery of lipophilic drugs. Two types of surfactants were used to enhance the skin electroporation. Tween 80 (0.2 g/L) and sodium dodecyl sulphate (SDS, 3 mg/mL) improve the solubility and diffusion rate of the drug in the hydrophobic local transport regions and reduce the entrapment of piroxicam in the skin. The transdermal delivery rate of piroxicam is increased 30- to 50-fold. However, the entrapment of piroxicam in the skin still occurred when Tween 80 was added. The SDS provides higher and more stable transdermal delivery rates of piroxicam than Tween 80, and also reduces the entrapment of piroxicam in the skin.

  7. Piroxicam inhibits herpes simplex virus type 1 infection in vitro.

    Science.gov (United States)

    Astani, A; Albrecht, U; Schnitzler, P

    2015-05-01

    Piroxicam is a potent, nonsteroidal, anti-inflammatory agent (NSAID) which also exhibits antipyretic activity. The antiviral effect of piroxicam against herpes simplex virus type 1 (HSV-1) was examined in vitro on RC-37 monkey kidney cells using a plaque reduction assay. Piroxicam was dissolved in ethanol or dimethylsulfoxide (DMSO) and the 50% inhibitory concentration (IC50) was determined at 4 μg/ml and 75 μg/ml, respectively. The IC50 for the standard antiherpetic drug acyclovir was determined at 1.6 μM. At non-cytotoxic concentrations of these piroxicam solutions, plaque formation was significantly reduced by 62.4% for ethanolic piroxicam and 72.8% for piroxicam in DMSO. The mode of antiviral action of these drugs was assessed by time-on-addition assays. No antiviral effect was observed when cells were incubated with piroxicam prior to infection with HSV-1 or when HSV-1 infected cells were treated with dissolved piroxicam. Herpesvirus infection was, however, significantly inhibited when HSV-1 was incubated with piroxicam prior to the infection of cells. These results indicate that piroxicam affected the virus before adsorption, but not after penetration into the host cell, suggesting that piroxicam exerts a direct antiviral effect on HSV-1. Free herpesvirus was sensitive to piroxicam in a concentration-dependent manner and the inhibition of HSV-1 appears to occur before entering the cell but not after penetration of the virus into the cell. Considering the lipophilic nature of piroxicam, which enables it to penetrate the skin, it might be suitable for topical treatment of herpetic infections.

  8. Formation of Piroxicam Polymorphism in Solution Crystallization

    DEFF Research Database (Denmark)

    Bruun Hansen, Thomas; Qu, Haiyan

    2015-01-01

    also explored, and new insights into polymorphic control are documented and discussed. The crystal landscape was mapped for cooling crystallization of piroxicam from acetone/water mixtures (0.5 K/min) and for antisolvent crystallization from acetone with water as the antisolvent. Varying cooling rates...

  9. Photosensitivity to piroxicam: absence of cross-reaction with tenoxicam

    OpenAIRE

    Gonçalo, Margarida; Figueiredo, A; Tavares, P.; Fontes-Ribeiro, CA; Teixeira, F.; Poiares-Baptista, A

    1992-01-01

    We studied 2 groups of patients. One group of 10 patients had a photosensitive eruption to piroxicam. Another group of 24 patients had positive patch test reactions to thimerosal and thiosalicylic acid and had never taken piroxicam or tenoxicam. Patients were patch tested with thimerosal 0.1% pet., thiosalicylic acid 0.1% pet., salicylic acid 2.0% pet., piroxicam 1 and 5% pet. and tenoxicam 1 and 5% pet. Photopatch tests were also performed with piroxicam and tenoxicam. All 10 patients with p...

  10. Piroxicam decreases postirradiation colonic neoplasia in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Northway, M.G.; Scobey, M.W.; Cassidy, K.T.; Geisinger, K.R. (Wake Forest Univ., Winston Salem, NC (USA))

    1990-12-01

    This study evaluated the effects of the nonsteroidal antiinflammatory agent piroxicam on chronic radiation proctitis in the rat. Forty female Wistar rats received a 2250-cGy dose of irradiation to the distal 2 cm of the colon. Twenty received piroxicam 8.0 mg/kg orally 30 minutes before exposure and 24 hours after exposure; 20 rats served as irradiated controls. All animals were evaluated by colonoscopy 1 and 3 weeks postexposure and every third week until death or killing at 1 year. At killing, colons were removed for light microscopic examination. One year postirradiation results showed no differences in mortality, vascular changes, acute inflammation, colitis cystica profunda, or rectal stricture between the control and piroxicam-treated groups. However, at 1 year postirradiation the control group demonstrated neoplasia in 15 of 19 animals compared with eight of 20 animals in the piroxicam-treated group. The first endoscopic appearance of colonic neoplasm occurred at 15 weeks postirradiation in one control irradiated rat whereas the first evidence of endoscopic neoplasm in the piroxicam-treated group did not occur until 36 weeks postirradiation. Histologic examination documented a tendency toward a greater presence of adenocarcinomas in the control group compared with the piroxicam-treated group. The authors conclude that piroxicam treatment significantly decreased the incidence of colonic neoplasia in general as well as delayed the endoscopic appearance of colonic neoplasia in rats after pelvic irradiation. 41 references.

  11. Design and Evaluation of Piroxicam Microemulsion

    Directory of Open Access Journals (Sweden)

    Mr. Harsh J. Trivedi

    2012-04-01

    Full Text Available The main objective of the present research work was to improve the oral bioavailability of BCS class IIdrugs which are known to have low solubility but have high permeability. In the present study,Piroxicam has been chosen as a model drug wmany dose related side effects. If the bioavailability of this drug is increased reduction of the dose andthe dose related side effects can be controlled and this would lead to more affordable thmicroemulsion formulation for enhancing the bioavailability of Piroxicam was developed and evaluated.A microemulsion is one of the novel pharmaceutical interests for drug delivery, and is normallycomposed of oil, water, surfactants and codifferent ratio of oil to surfactant mixtures (surfactant + cozone was recorded in the PseudoSphase. The ratio of components (oil, surfactant, coConductivity, Clarity, Dilution shock,Particle Size. The higher permeability achieved with the microemulsion systems compared to themarketed product (Piroxpermeability bmembrane due to the surfactants, and may be used as a vehicle for enhanced delivery of BCS class IIdrugs.

  12. Anti-Inflammatory and Gastroprotective Evaluation of Prodrugs of Piroxicam

    Directory of Open Access Journals (Sweden)

    Vivekkumar K. Redasani

    2014-01-01

    Full Text Available Therapeutically potential prodrugs of piroxicam were synthesized by effective masking of enolic hydroxyl group through generation of ester congeners. The reaction facilitated using N,N′-dicyclohexylcarbodiimide coupled with acetic acid, benzoic acid, p-toluic acid, m-toluic acid, and cinnamic acid. Synthesized prodrugs were characterized for confirmation of the said structures. The modification of piroxicam showed better anti-inflammatory activity as evoked by all prodrugs. Interestingly, compound 3e, cinnamic acid ester prodrug, depicted 75 percent inhibition of rat paw edema as compared to 56 percent for parent piroxicam at 6 h of study. The present work proves the applicability not only with increased anti-inflammatory activity, but also with marked attenuation in ulcerogenicity. Novel prodrug 3e, cinnamic acid derivative, was found to be the least ulcerogenic having ulcer index of 0.67 as compared to parent drug piroxicam with 2.67.

  13. Protein microspheres as suitable devices for piroxicam release.

    Science.gov (United States)

    Silva, Raquel; Ferreira, Helena; Carvalho, Ana C; Gomes, Andreia C; Cavaco-Paulo, Artur

    2012-04-01

    Bovine serum albumin-piroxicam (BSA-piroxicam) and human serum albumin-piroxicam (HSA-piroxicam) microspheres were sonochemically prepared and characterized. The use of polyvinyl alcohol (PVA) lead to an improvement of formulation characteristics, including smaller size, lower polydispersity index (PDl), higher entrapment efficiency and higher stability. The release kinetics of these proteinaceous microspheres was determined in presence of protease, indicating an anomalous drug transport mechanism (diffusion and polymer degradation). In presence of higher protease concentration, BSA microspheres exhibit Case II transport, leading to zero order release (protein degradation). These proteinaceous devices did not show cytotoxicity against human skin fibroblasts in vitro, for range concentrations below to 300 mg L(-1), greatly supporting their potential application in the treatment of inflammatory diseases.

  14. A comparative study of flurbiprofen and piroxicam in osteoarthritis.

    Directory of Open Access Journals (Sweden)

    Misra N

    1992-10-01

    Full Text Available In this single-blind, multiple-dose study the efficacy and tolerability of flurbiprofen was compared with that of piroxicam in 60 adult patients suffering from osteoarthritis of the knee. The patients were randomly allocated to receive either flurbiprofen 100 mg twice daily or piroxicam 20 mg once daily for a period of four weeks. Clinical assessments w.r.t. pain, tenderness, stiffness, swelling and general activity of patient were carried out prior to initiation of trial therapy and thereafter at weekly intervals for four weeks. The findings were graded. Though significant improvements as compared to baseline data occurred in both the treatment groups, flurbiprofen was found to be superior to piroxicam in improving pain on movement and at rest (p < 0.05. The incidence of side effects was less in the group receiving flurbiprofen (6% compared to 47% observed with piroxicam.

  15. Biowaiver monographs for immediate release solid oral dosage forms: piroxicam.

    Science.gov (United States)

    Shohin, Igor E; Kulinich, Julia I; Ramenskaya, Galina V; Abrahamsson, Bertil; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Groot, D W; Barends, Dirk M; Dressman, Jennifer B

    2014-02-01

    Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing piroxicam in the free acid form are reviewed. Piroxicam solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA), and corresponding dissolution data are taken into consideration. The available data suggest that according to the current biopharmaceutics classification system (BCS) and all current guidances, piroxicam would be assigned to BCS Class II. The extent of piroxicam absorption seems not to depend on manufacturing conditions or excipients, so the risk of bioinequivalence in terms of area under the curve (AUC) is very low, but the rate of absorption (i.e., BE in terms of Cmax ) can be affected by the formulation. Current in vitro dissolution methods may not always reflect differences in terms of Cmax for BCS Class II weak acids; however, minor differences in absorption rate of piroxicam would not subject the patient to unacceptable risks: as piroxicam products may be taken before or after meals, the rate of absorption cannot be considered crucial to drug action. Therefore, a biowaiver for IR piroxicam solid oral dosage form is considered feasible, provided that (a) the test product contains only excipients, which are also present in IR solid oral drug products containing piroxicam, which have been approved in ICH or associated countries, for instance, those presented in Table 3 of this paper; (b) both the test and comparator drug products dissolve 85% in 30 min or less at pH 1.2, 4.5, and 6.8; and (c) the test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. When not all of these conditions can be fulfilled, BE of the products should be established in vivo.

  16. Photo- and thermal degradation of piroxicam in aqueous solution

    Directory of Open Access Journals (Sweden)

    M Aminuddin

    2011-01-01

    Full Text Available Light and temperature have considerable effect on the degradation of piroxicam in aqueous solutions. The pH and acetate buffer ions also affect the degradation process. The apparent first-order rate constants for the photochemical and thermal degradation of piroxicam have been determined as 2.04-10.01 and 0.86-3.06×10−3 min−1 , respectively. The first-order plots for the degradation of piroxicam showed good linearity within a range of 20-50% loss of piroxicam at pH 2.0-12.0. The rate-pH profile for the photodegradation of piroxicam is a U-shaped curve and for the thermal degradation a bell-shaped curve in the pH range of 2.0-12.0. The thermal degradation of piroxicam was maximum around pH 6.0. It is increased in the presence of acetate ions but was not affected by citrate and phosphate ions.

  17. Stability studies on piroxicam encapsulated niosomes.

    Science.gov (United States)

    Ertekin, Zehra Ceren; Bayindir, Zerrin Sezgin; Yuksel, Nilufer

    2015-01-01

    Drug delivery systems which yield ideal treatments are currently the center of interest for researchers. Niosomes have numerous advantages over other drug delivery systems. However, stability issue is not clear yet and is a serious drawback for niosomes. In this study, the stability of niosomes was the center of interest. Piroxicam which was chosen as the model drug was loaded to niosomes. Niosomes were prepared by thin-film method and different forms (aqueous dispersion, lyophilized powder and lyophilized powder with cryoprotectant) of the original niosome formulation were prepared. The samples were stored either at 5°C±3°C or 25°C±2°C/60% RH±5% RH for 3 months. The drug leakage percent, particle size and distribution, zeta potential, drug release profiles were determined and niosomes were visualized under optic microscope. Niosome formulation provided sustained release of piroxicam. The drug leakage from stored niosomes was observed at the level of 1.56-6.63 %. Individual vesicle images were obtained for all samples by optical microscope. However, particle size of niosomes was increased upon storage. The zeta potential values were neither related to time nor physical form. Drug release profiles and amounts were quite similar for all forms of niosomes and the original formulation but a slight decrease was noticed on drug release amounts by time. This indicates that niosomes become more rigid by time. Although the ideal storage was obtained with lyophilized niosomes at 5±3°C in this study, the usage of suitable cryoprotectant and optimized lyophilization process should be further evaluated.

  18. Effect of glucosamine HCl on dissolution and solid state behaviours of piroxicam upon milling.

    Science.gov (United States)

    Al-Hamidi, Hiba; Edwards, Alison A; Douroumis, Dionysis; Asare-Addo, Kofi; Nayebi, Alireza Mohajjel; Reyhani-Rad, Siamak; Mahmoudi, Javad; Nokhodchi, Ali

    2013-03-01

    Piroxicam is a non-steroidal anti-inflammatory drug that is characterised by low solubility and high permeability. In order to improve the drug dissolution rate, the co-grinding method was used as an approach to prepare piroxicam co-ground in the carriers such as glucosamine hydrochloride. As, this amino sugar (glucosamine HCl) has been shown to decrease pain and improve mobility in osteoarthritis in joints, therefore, the incorporation of glucosamine in piroxicam formulations would be expected to offer additional benefits to patients. The effect of the order of grinding on the dissolution of piroxicam was also investigated. Co-ground drug and glucosamine were prepared in different ratios using a ball mill. The samples were then subjected to different grinding times. In order to investigate the effect of the grinding process on the dissolution behaviour of piroxicam, the drug was ground separately in the absence of glucosamine. Mixtures of ground piroxicam and unground D-glucosamine HCl were prepared. Physical mixtures of piroxicam and glucosamine were also prepared for comparison. The properties of prepared co-ground systems and physical mixtures were studied using a dissolution tester, FTIR, SEM, XRPD and DSC. These results showed that the presence of glucosamine HCl can increase dissolution rate of piroxicam compared to pure piroxicam. Generally, all dissolution profiles showed the fastest dissolution rate when ground piroxicam was mixed with unground glucosamine. This was closely followed by the co-grinding of piroxicam with glucosamine where lower grinding times showed the fastest dissolution. The solid state studies showed that the grinding of piroxicam for longer times had no effect on polymorphic form of piroxicam, whereas mixtures of piroxicam-glucosamine ground for longer times (60 min) converted piroxicam polymorph II to polymorph I.

  19. Dissolution rate enhancement of piroxicam by ordered mixing.

    Science.gov (United States)

    Saharan, Vikas Anand; Choudhury, Pratim Kumar

    2012-07-01

    Micronized piroxicam was mixed with lactose, mannitol, sorbitol, maltitol and sodium chloride to produce ordered mixture in a glass vial by manual hand shaking method. The effect of excipients, surfactant, superdisintegrant, drug concentration and carrier particle size on dissolution rate was investigated. Dissolution rate studies of the prepared ordered mixtures revealed that all water soluble excipients increased the dissolution rate of piroxicam when compared to the dissolution rate of piroxicam or its suspension. Ordered mixture formulation PLF4, consisting of lactose as water soluble excipient, SSG (8% w/s) and SLS (1% w/w), released piroxcam at a very fast rate so much so that about 90% of the composition had passed into solution within 2 min. The order of the dissolution rate enhancement for ordered mixtures of various water soluble excipients was: lactose > mannitol > maltitol > sorbitol > sodium chloride. Carrier granules of size 355-710 µm were most effective in increasing the dissolution rate of drug from ordered mixtures. Decreasing the carrier particle size reduced drug dissolution from ordered mixtures. The dissolution rate of ordered mixtures consisting of 1-5% w/w piroxicam was superior to dissolution rate of piroxicam suspension. The dissolution data fitting and the resulting regression parameters indicated Hixson Crowell, cube root law, as the best fit to drug release data of ordered mixtures.

  20. Photostability of piroxicam in the inclusion complex with 2-hydroxypropyl-β-cyclodextrin

    Directory of Open Access Journals (Sweden)

    Nikolić Vesna D.

    2014-01-01

    Full Text Available The aim of this work is the protection of piroxicam from photodegradation by forming inclusion complex with 2-hydroxypropyl-β-cyclodextrin. Piroxicam:2-hydroxypropyl-β-cyclodextrin molecular inclusion complex was prepared by coprecipitation method with molar ratio of 1:1. Structural characterization of the complex, the corresponding physical mixture and complexing agents of piroxicam and 2-hydroxypropyl-β-cyclodextrin was carried out by X-ray diffraction (XRD, proton nuclear magnetic resonance (1H NMR and Fourier transform infrared spectroscopy (FTIR. Photosensitivity to daylight for piroxicam and piroxicam:2-hydroxypropyl-β-cyclodextrin inclusion complex was investigated by Fourier-transform infrared spectroscopy. The investigations show that higher photostability of piroxicam was achieved in complex than in non-complexed piroxicam.

  1. [Acute generalized exanthematous pustulosis induced by piroxicam].

    Science.gov (United States)

    Bissinger, Ingrid; Matute-Turizo, Gustavo; Mejía-Barreneche, María Natalia

    2016-01-01

    Antecedentes: Entre 62 y 90% de los casos de pustulosis exantemática generalizada aguda son causados por medicamentos. Su inicio es rápido con pústulas generalizadas, fiebre, conteo de neutrófilos en sangre mayor de 7000; la resolución de las pústulas es espontánea en menos de 15 días. Se describe un caso asociado a piroxicam. Caso clínico: Hombre de 36 años de edad con eritema inicial en tórax y abdomen, acompañado de ardor, sin fiebre, que posteriormente se extendió a antebrazos, brazos y muslos; con edema de cara. Una semana antes había consumido piroxicam por dolor lumbar; al momento de su hospitalización recibía antihistamínicos, esteroides tópicos y sistémicos. El hemoleucograma mostró leucocitos de 8920, eosinófilos de 600, neutrófilos de 6600, IgE sérica total de 188 mg/L, proteína C reactiva de 2.9 mg/L, sin compromiso hepático, renal ni pulmonar. Se inició tratamiento con antihistamínicos y ranitidina intravenosos, solución salina, vaselina tópica más mupirocina tópica y esteroides sistémicos. Al segundo día de hospitalización, los neutrófilos aumentaron a 9000 y la proteína C reactiva a 3.3 mg/L. La puntuación para validar pustulosis exantemática aguda en el paciente fue de 8, indicativa de diagnóstico definitivo. Conclusiones: El diagnóstico diferencial debe establecerse principalmente con psoriasis pustulosa. El pronóstico en general es bueno, como sucedió con el caso informado.

  2. Piroxicam treatment augments bone abnormalities in interleukin-10 knockout mice

    DEFF Research Database (Denmark)

    Holgersen, Kristine; Dobie, Ross; Farquharson, Colin;

    2015-01-01

    inflammation in an experimental colitis model. METHODS: Colitis was induced in interleukin-10 knockout mice (PAC IL-10 k.o.) by peroral administration of piroxicam for 12 days. The degree of colitis was assessed by clinical, macroscopic, and microscopic evaluation. Trabecular and cortical bone...... and focal transmural inflammation, which was consistent with Crohn's disease-like pathology. The gut inflammation was accompanied by a 14% and 12% reduction in trabecular thickness relative to piroxicam-treated wild type and untreated wild type mice, respectively (P

  3. Toxico-Neurological Effects of Piroxicam in Monogastric Animals

    Science.gov (United States)

    Saganuwan, Saganuwan Alhaji; Orinya, Orinya Agbaji

    2016-01-01

    Piroxicam is a benzothiazine compound with anti-inflammatory, antipyretic, and analgesic properties. Because of the very high efficacy of piroxicam and its increasing use in the treatment of carcinomas in dogs and cats, there is a need for acute toxicity study of piroxicam in monogastric animals and its potential for causing secondary poisoning in puppies. Piroxicam manufactured by Shanxi Federal Pharmaceutical Co, Ltd. was used for this study. Revised up-and-down procedure was used for the estimation of median lethal dose in mouse (259.4 ± 51.9 mg/kg), rat (259.4 ± 69.6 mg/kg), rabbit (707.5 ± 130.8 mg/kg), cat (437.5 ± 128.1 mg/kg), guinea pig (218.7 ± 64.1 mg/kg), monkey (733.3 ± 83.3 mg/kg), broiler (285.3 ± 62.5 mg/kg), hen (638.3 ± 115.4 mg/kg), turkey (707.5 ± 130.8 mg/kg), pigeon (375 ± 55.9 mg/kg), and duck (311.3 ± 46.6 mg/kg). The acute toxicity signs of piroxicam at doses 207.5 mg/kg and above observed in the animals are torticollis, opisthotonos, somnolence, lethargy, diarrhea, gastroenteritis, generalized internal bleeding, anemia, congestion of the lung and liver, flaccid paralysis, cheesy lung, urinary incontinence, engorged urinary bladder, convulsive jerking of the limbs, lying in ventral recumbency, gasping for air, roaring, and death. Three out of six puppies died after being fed the carcasses of poisoned turkey, duck, and hen administered piroxicam at doses of 1000, 415, and 1000 mg/kg, respectively. White flaky cheesy materials observed in turkeys were also observed in the gastrointestinal content of the puppies. Paleness of carcasses, watery crop content, dryness of pericardium, gastroenteritis, intestinal perforation, and whitish pericardium were observed in broilers. There were effusions in thoracic and abdominal cavities as seen in all other carcasses poisoned primarily by piroxicam. Administration of atropine (0.02 mg/kg) led to survival of the remaining puppies. In conclusion, piroxicam is very to moderately toxic in

  4. Piroxicam y cambios ováricos de cabras adultas

    OpenAIRE

    Rafaela Segundo Pérez; Leonor Miranda Jiménez; Alejandro Ángel Gómez Danés; Miguel Ángel Casiano Ventura; Adrián Raymundo Quero Carrillo; Paulino Pérez Rodríguez

    2016-01-01

    La función de los ovarios puede alterarse por inhibidores de la enzima ciclooxigenasa (COX). La aplicación de piroxicam, antiinflamatorio no esteroideo e inhibidor de COX es de amplio uso veterinario (AINE) y puede alterar la función de los ovarios. El objetivo de esta investigación fue evaluar los cambios extra e intraováricos en cabras adultas en respuesta a piroxicam. En seis cabras adultas de entre 35 y 40 kg de peso vivo, se sincronizaron estros y ovulación, mediante la colocación de CID...

  5. Naproxen sodium and piroxicam in acute musculo-skeletal disorders.

    Science.gov (United States)

    Bouchier-Hayes, T. A.

    1984-01-01

    Of one hundred patients originally entered for this trial eighty-three with acute musculo-skeletal disorders were treated with either naproxen sodium (SYNFLEX, Syntex), 550 mg initially followed by 275 mg four times daily, or piroxicam (FELDENE, Pfizer), 20 mg twice daily for two days then 20 mg once daily. Patients were assessed at admission, on day 4 and on day 8. Pain on passive movement, tenderness, swelling and limitation of function were evaluated and patients also completed a daily self-assessment form. Pain relief was recorded by the patient for 4 hours following the first dose. No statistically significant differences were detected between the treatment groups for any of the efficacy measurements. Of the eighty-three patients analysed, twenty-four patients withdrew from treatment twenty of whom did not need further analgesia (13 in the naproxen sodium group and 7 in the piroxicam group). Three patients experienced side-effects; all were in the piroxicam group, and one patient withdrew from the study because of epigastric pain. Both naproxen sodium and piroxicam proved effective in the treatment of musculo-skeletal disorders. Naproxen sodium did not give rise to any side-effects. Images p80-a PMID:6466934

  6. The mechanism of antidepressant-like effects of piroxicam in rats

    Directory of Open Access Journals (Sweden)

    Ronise Martins Santiago

    2015-01-01

    Full Text Available Objective: To investigate the antidepressant-like effect of piroxicam with a focus on serotonergic neurotransmission. Materials and Methods: Rats were randomly distributed into the following groups: 0.9% saline control; 3 mg/kg pizotifen; 10 mg/kg sertraline; 10 mg/kg piroxicam; 10 mg/kg sertraline + 10 mg/kg piroxicam; 10 mg/kg sertraline + 3 mg/kg pizotifen; and 10 mg/kg piroxicam + 3 mg/kg pizotifen. All the drugs were dissolved in 0.9% saline. Three administrations of the drugs (piroxicam and sertraline were performed 1, 5 and 24 h before testing the animals in the open field followed by the forced swim test (FST. Piroxicam and sertraline were administered orally by gavage and pizotifen was administered intraperitoneally 30 min before gavage. Immediately after the FST, the hippocampi were rapidly dissected for neurochemical analysis in high-performance liquid chromatography. Results: Acute treatment with piroxicam promoted an antidepressant-like effect in the FST, which was associated with an increase in serotonin levels in the hippocampus. This effect was potentiated in the piroxicam + sertraline group but counteracted by administration of the non-selective serotonin receptor antagonist pizotifen. Conclusion: These results suggest that the antidepressant-like effect of piroxicam in the FST is mediated by the serotonin system; however, by different mechanisms from those of sertraline.

  7. Enhancement of dissolution rate of piroxicam by electrospinning technique

    Science.gov (United States)

    Raziya Begum, S. K.; Mohan Varma, M.; Raju, D. B.; Prasad, R. G. S. V.; Phani, A. R.; Jacob, Biju; Salins, Paul C.

    2012-12-01

    The use of electrospun nanofibers to enhance dissolution of poorly soluble drugs could be a novel strategy in future for pharmaceutical applications. In the present work electrospun nanofibers were prepared as a novel system for enhancing the delivery of piroxicam, a non-steroidal anti-inflammatory drug (NSAID). These nanofibers were prepared from polyvinyl pyrrolidone (PVP) (pharmaceutical grade), a biodegradable polymer, to obtain a solution with drug:polymer ratio of 1:4. The release rate of the piroxicam nanofibers was studied in simulated gastric fluid. Fourier transform infrared (FTIR) and scanning electron microscopy (SEM) are used to evaluate the chemical and physical nature. The results showed that the release rates were twice increased in comparison with the pure drug. However, the blend of drug and polymer could be varied to optimize the release rates depending upon the need and formulation

  8. Enhanced transdermal permeability of piroxicam through novel nanoemulgel formulation

    OpenAIRE

    2014-01-01

    Background: Piroxicam is a non-steroidal anti-inflammatory drug belongs to BCS class II drugs having poor solubility and is associated with a number of undesirable side-effects on the stomach and kidneys in addition to gastric mucosal damage. Aim: The present work was to develop and characterize nanoemulgel formulation as transdermal delivery system for poorly water soluble drug, in order to overcome the troubles associated with its oral delivery and to circumvent the need of chemical penetra...

  9. Antidepressant-like effect of celecoxib piroxicam in rat models of depression.

    Science.gov (United States)

    Santiago, Ronise M; Barbiero, Janaína; Martynhak, Bruno J; Boschen, Suelen L; da Silva, Luisa M; Werner, Maria F P; Da Cunha, Claudio; Andreatini, Roberto; Lima, Marcelo M S; Vital, Maria A B F

    2014-06-01

    Beyond the current hypothesis of depression, several new biological substrates have been proposed for this disorder. The present study investigated whether the anti-inflammatory drugs celecoxib and piroxicam have antidepressant activity in animal models of depression. After acute administration, we observed antidepressant-like effects of celecoxib (10 mg/kg) and piroxicam (10 mg/kg) in the modified forced swim test in rats. Piroxicam increased serotonin and norepinephrine levels in the hippocampus. Prolonged (21-day) treatment with celecoxib (10 mg/kg) and piroxicam (10 mg/kg) rescued sucrose preference in a chronic mild stress model of depression. Additionally, the chronic mild stress-induced reduction of hippocampal glutathione was prevented by treatment with celecoxib and piroxicam. Superoxide dismutase in the hippocampus was increased after chronic mild stress compared with the non-stressed saline group. The non-stressed celecoxib and piroxicam groups and stressed piroxicam group exhibited an increase in hippocampal superoxide dismutase activity compared with the stressed saline group. Lipid hydroperoxide was increased in the stressed group treated with vehicle and non-stressed group treated with imipramine but not in the stressed groups treated with celecoxib and piroxicam. These results suggest that the antidepressant-like effects of anti-inflammatory drugs might be attributable to enhanced antioxidant defenses and attenuated oxidative stress in the hippocampus.

  10. Evaluation of adverse events in cats receiving long-term piroxicam therapy for various neoplasms.

    Science.gov (United States)

    Bulman-Fleming, Julie C; Turner, T R; Rosenberg, Mona P

    2010-04-01

    The role of cyclo-oxygenase 2 (COX-2) and prostaglandins (PG) in carcinogenesis has been documented in many species. Piroxicam has shown efficacy against several neoplasms and is frequently prescribed for chronic use. There are no studies investigating chronic piroxicam administration in cats and the chronic use of non-steroidal anti-inflammatory agents in this species has long been cautioned against. This retrospective study aimed to evaluate adverse effects in cats receiving long-term daily piroxicam. Seventy-three cats received daily piroxicam at doses of 0.13-0.41mg/kg. Treatment duration ranged from 1 to 38 months. Treatment with piroxicam was found to significantly increase frequency of vomiting during the first month of therapy, though this was most significant for cats receiving concurrent chemotherapy. Piroxicam administration was not significantly associated with hematologic, renal or hepatic toxicities. Adverse events were not correlated with dosage. Adverse events were reported in 29% of cats, and were generally mild and transient. Eight percent discontinued piroxicam due to adverse reaction, and 4% due to difficult administration. This study indicates that long-term daily piroxicam is generally well tolerated in cats at conventional doses.

  11. Piroxicam-mediated modulatory action of 5-hydroxytryptamine serves as a "brake" on neuronal excitability in ischemic stroke

    Directory of Open Access Journals (Sweden)

    Pallab Bhattacharya

    2015-01-01

    Full Text Available Our previous studies indicated an increase in extracellular γ-aminobutyric acid (GABA in rodent′s ischemic brain after Piroxicam administration, leading to alleviation of glutamate mediated excitotoxicity through activation of type A GABA receptor (GABAA. This study was to investigate if GABAA activation by Piroxicam affects extracellular 5-hydroxytryptamine or not. High performance liquid chromatography revealed that there was a significant decrease in extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum in Piroxicam pre-treated rat brains. This suggests a probable role of Piroxicam in reducing extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum possibly due to the GABAA activation by Piroxicam.

  12. Piroxicam-Induced hepatic and renal Histopathological changes in mice

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    Amany Tohamy

    2007-02-01

    Full Text Available Piroxicam is a non-steroidal anti-inflammatory drug widely used in rheumatic diseases. The aim of this study was to investigate Piroxicam-induced histopathological changes in livers and kidneys of male albino mice. Methods: Animals were classified into a control group and 4 treated groups. Piroxicam was injected intraperitoneally using 0.3 mg/kg every day for four weeks. Each week a group of mice was sacrificed. Liver and kidneys were obtained for histological and histochemical examination.Animals were classified into a control group and 4 treated groups. Piroxicam was injected intraperitoneally using 0.3 mg/kg every day for four weeks. Each week a group of mice was sacrificed. Liver and kidneys were obtained for histological and histochemical examination.Results: Liver sections appeared with inflammatory cellular infiltration, vacuolated hepatocytes, dilated sinusoids, and increased number of Kupffer cells. Kidney sections appeared with some cellular inflammations. The glomeruli were shrunk resulting in widening of the urinary space. Oedema and vacuolations were noticed in the tubular cells. There was a positive correlation between these pathological changes and the increased treatment periods. Histochemical staining revealed that glycogen and protein contents had decreased in the hepatocytes. This depletion worsened gradually in liver cells after two, three, and four weeks. Similar depletion of the glycogen content was observed in kidney tissue. However, protein content appeared to be slightly decreased in the kidney tubules and glomeruli. Incensement of coarse chromatin in the nuclei of hepatocytes, Kupffer cells and most inflammatory cells were detected by Fuelgen method. Kidney tissues appeared with a severe decrease in coarse chromatin in the nuclei.Liver sections appeared with inflammatory cellular infiltration, vacuolated hepatocytes, dilated sinusoids, and increased number of Kupffer cells. Kidney sections appeared with some cellular

  13. Piroxicam y cambios ováricos de cabras adultas

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    Rafaela Segundo Pérez

    2016-01-01

    Full Text Available La función de los ovarios puede alterarse por inhibidores de la enzima ciclooxigenasa (COX. La aplicación de piroxicam, antiinflamatorio no esteroideo e inhibidor de COX es de amplio uso veterinario (AINE y puede alterar la función de los ovarios. El objetivo de esta investigación fue evaluar los cambios extra e intraováricos en cabras adultas en respuesta a piroxicam. En seis cabras adultas de entre 35 y 40 kg de peso vivo, se sincronizaron estros y ovulación, mediante la colocación de CIDR (dispositivo intravaginal de liberación controlada de P4 durante 11 días, al retirar el CIDR se aplicaron prostaglandinas F2α y 400 UI de eCG (inducción de la ovulación. Antes (24 h, de la inducción de ovulación al grupo testigo y tratado (n=3 se les hicieron cuatro aplicaciones intramusculares de un ml de solución salina o piroxicam (1.5 mg-1 kg de peso vivo con intervalo de 24 h. Posterior a la primera aplicación de piroxicam (144 h se extrajeron los ovarios. Se colectaron muestras sanguíneas cada 24 h; desde 48 h antes de la inducción de la ovulación y, hasta la ovariectomía. En ovario derecho e izquierdo se cuantificó el número y tamaño de folículos y cuerpos lúteos superficiales. En 16 cortes histológicos de cada ovario, se evaluaron las mismas estructuras con localización intraovárica. En suero sanguíneo se determinó la concentración sérica de progesterona (P4 y estradiol (E2. En los datos de folículos y CL se realizó la prueba de suma de rangos de Wilcoxon. Mientras que, P4 y E2 se analizaron utilizando modelos para datos con medidas repetidas (modelos mixtos lineales, los cuales fueron ajustados usando el programa estadísto R. La significancia en los resultados se consideró con α< 0.05. La aplicación de piroxicam disminuyó el número de folículos intraováricos (P< 0.0001 y el de CL intraováricos en desarrollo (P=0.04. Los niveles de P4 y E2 no se modificaron por aplicación de piroxicam (P=0.2, aunque, P4

  14. Preparation, characterization, and stability studies of piroxicam-loaded microemulsions in topical formulations.

    Science.gov (United States)

    Abd-Allah, F I; Dawaba, H M; Ahmed, A Ms

    2010-08-01

    The main purpose of this work was to determine the in vitro release of piroxicam in microemulsion formulations from different pharmaceutical topical preparations including different gel bases, such as, methyl cellulose (MC), carboxy methyl cellulose (CMC), hydroxypropyl methyl cellulose (HPMC), Carbopol 934, Carbopol 940, and Pluronic F-127 bases. The effect of the employed gel bases on the in vitro release profiles of piroxicam was examined to choose the base which gave the highest in vitro release. The kinetic treatments and parameters derived from in vitro release of piroxicam formulations were calculated according to different kinetic orders or systems. These gel formulations were selected for rheological and stability studies. Stability studies were conducted to investigate the change in drug content, viscosity, and pH of the semisolid formulations. The results showed that, the incorporation of piroxicam in microemulsion formulas could lead to enhancement of piroxicam release profiles by allowing constant and regular in vitro release. Three percent MC gel base showed the highest release of piroxicam-microemulsion after 180 min (97.70%) followed by 3% HPMC (94.0%) when compared to bases containing piroxicam alone. All the medicated gel bases containing piroxicam exhibit pseudoplastic flow with thixotropic behavior. The degradation of piroxicam from its topical formulations was found to be a zero-order reaction based on the mean value of correlation coefficients. All formulations were quite stable. The shelf life of the gel containing HPMC base was about 2.85 years. Considering the in vitro release, rheological properties and shelf life, HPMC gel base containing 0.5% piroxicam in a microemulsion formula was the best among the studied formulations.

  15. Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement

    Science.gov (United States)

    Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant

    2013-03-01

    Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide- co-glycolide) (PLGA) microparticles (size 1-4 μm, encapsulation efficiency 80-85 %) and nanoparticles (size 151.6 ± 28.6 nm, encapsulation efficiency 92.17 ± 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.

  16. Solid state transformations in consequence of electrospraying--a novel polymorphic form of piroxicam.

    Science.gov (United States)

    Nyström, Maija; Roine, Jorma; Murtomaa, Matti; Mohan Sankaran, R; Santos, Hélder A; Salonen, Jarno

    2015-01-01

    The aim of the research was to verify that electrospraying of piroxicam yielded a new polymorphic form of this drug. In the experiments, piroxicam was dissolved in chloroform and the solution was atomised electrostatically. Subsequently, the charged droplets were neutralised and dried. The solid drug particles were collected and analysed by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, high performance liquid chromatography, and infrared and Raman spectroscopy. The X-ray diffractogram measured for the electrosprayed piroxicam particles did not match with any of the known piroxicam crystal structures (Cambridge Crystallographic Data Centre). The variable temperature X-ray diffraction showed that the structure recrystallised completely into piroxicam polymorphic formI during heating. No degradation products or solvate removal was detected by high performance liquid chromatography and thermal analysis. The infrared and Raman spectra of the electrosprayed piroxicam were compared to those of formI, and some notable differences in the peak positions, shapes and intensities were detected. The results indicate that electrospraying leads to piroxicam crystallisation in a currently unknown polymorphic form.

  17. Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant, E-mail: pmishra@dbeb.iitd.ac.in [Indian Institute of Technology Delhi, Department of Biochemical Engineering and Biotechnology (India)

    2013-03-15

    Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide-co-glycolide) (PLGA) microparticles (size 1-4 {mu}m, encapsulation efficiency 80-85 %) and nanoparticles (size 151.6 {+-} 28.6 nm, encapsulation efficiency 92.17 {+-} 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.

  18. Effect of Piroxicam on ART Outcome: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Farnaz Sohrabvand

    2014-11-01

    Full Text Available Background: One of the most important factors affecting success rates in assisted reproductive techniques (ART besides the number of oocytes retrieved and high quality embryos derived from them is the technical aspects of embryo transfer. It seems that pretreatement with uterine relaxants can be helpful in preventing unpleasant cramps which can have an adverse effect on ART outcome. In this respect, some drugs such as prostaglandin inhibitors or sedatives have been evaluated but not confirmed yet remain controversial. This study was performed in order to assess the effect of administrating Piroxicam prior to embryo transfer on pregnancy rates in ART cycles. Materials and Methods: This pilot study was performed from August 2010 through December 2011 on 50 infertile women in ART cycles. Recombinant follicle stimulating hormone (rFSH with a long gonadotropin releasing hormone (GnRH analogue protocol were used for controlled ovarian hyperstimulation. The subjects were randomly allocated into two groups of 25 patients after obtaining written consent. Group A received a 10 mg Piroxicam capsule 30 minutes before embryo transfer and group B was the control group with no treatment. Data were analyzed by Chi-square and analysis of variance (ANOVA. Results: Pregnancy rate was 34% (n=17 totally, with 32% (n=8 in group A and 36% (n=9 in group B (p=0.75. Uterine cramps were experienced by 4 women (16% in group B, while none were reported by women in group A (p=0.037. Conclusion: It seems that Piroxicam administration 30 minutes prior to embryo transfer cannot increase pregnancy rates, but can prevent or reduce uterine cramps after the procedure.

  19. Acute generalized exanthematous pustulosis induced by piroxicam: A case report

    Directory of Open Access Journals (Sweden)

    Y Cherif

    2014-01-01

    Full Text Available Acute generalized exanthematous pustulosis (AGEP is a severe adverse cutaneous reaction characterized by an acute episode of sterile pustules over erythematous-edematous skin. The main triggering drugs are antibiotics, mainly beta-lactam and macrolides. Non-steroid anti-inflammatory drugs may rarely be responsible. We describe a case of a woman with AGEP, who presented with generalized pustulosis lesions after the use of piroxicam for renal colic. The diagnosis was confirmed by the clinical and histological correlations and the dermatosis resolved after withdrawal of the drug.

  20. Acute generalized exanthematous pustulosis induced by piroxicam: a case report.

    Science.gov (United States)

    Cherif, Y; Jallouli, Moez; Mseddi, M; Turki, H; Bahloul, Z

    2014-01-01

    Acute generalized exanthematous pustulosis (AGEP) is a severe adverse cutaneous reaction characterized by an acute episode of sterile pustules over erythematous-edematous skin. The main triggering drugs are antibiotics, mainly beta-lactam and macrolides. Non-steroid anti-inflammatory drugs may rarely be responsible. We describe a case of a woman with AGEP, who presented with generalized pustulosis lesions after the use of piroxicam for renal colic. The diagnosis was confirmed by the clinical and histological correlations and the dermatosis resolved after withdrawal of the drug.

  1. Piroxicam and other cyclooxygenase inhibitors: potential for cancer chemoprevention.

    Science.gov (United States)

    Earnest, D L; Hixson, L J; Alberts, D S

    1992-01-01

    Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) widely used for treatment of inflammatory arthritis. Recent experimental and clinical studies suggest that piroxicam, as well as other NSAIDs, may be useful for chemoprevention of colon cancer. While there is less information regarding NSAIDs for chemoprevention of urinary bladder malignancy, there are compelling data which suggest that this should be evaluated. A major effect of NSAIDs is inhibition of cyclooxygenase, the rate-limiting enzyme for conversion of arachidonic acid to important signal molecules, including prostaglandins, which profoundly affect cellular functions in many tissues. The initial enzyme reaction leading to formation of prostaglandin H can be accompanied by cooxidation of xenobiotics resulting in extrahepatic and local tissue production of reactive products which are carcinogenic. The end product prostaglandins, especially prostaglandin E2 (PGE2), are biological modifiers which can significantly affect cell proliferation and tumor growth. High levels of PGE2 stimulate growth of certain tumor cell lines while inhibition of prostaglandin synthesis with indomethacin or piroxicam can cause suppression. The mechanisms for this effect are unclear. Studies in cultured cells exposed to indomethacin show inhibition of G1-to-S phase progression of the cell cycle and a reduction in overall DNA synthesis. It is unclear whether this effect on cell growth results from some direct action of the NSAID or a reduction in prostaglandins or indirectly from modulation of important control signals, such as calcium flux. In addition to cyclooxygenase, NSAIDs can inhibit activity of other enzymes, including phosphodiesterases and cyclic GMP-AMP protein kinases, which may be central to cancer initiation and promotion. NSAIDs can also interfere with transmembrane ion fluxes and with cell-to-cell binding. Prostaglandins can modulate a variety of immunological responses and thereby play an important role in

  2. Effect of processing variables on dissolution and solubility of piroxicam: Hydroxypropyl-β -cyclodextrin inclusion complexes

    Directory of Open Access Journals (Sweden)

    Doijad R

    2007-01-01

    Full Text Available Influence of processing variables on the solid-state of a model drug, piroxicam in cyclodextrin-based system and its effect on dissolution behavior of the drug was investigated in the present study. Binary systems containing piroxicam and hydroxypropyl-β -cyclodextrin prepared by various processes, were characterized by FTIR, thermal stability, photo stability and dissolution studies. Hydroxypropyl-β -cyclodextrin enhanced the solubility of piroxicam and increased dissolution rates from the binary systems. The complex prepared by co-evaporation method was found to yield better dissolution rate and stability as characterized in present study over those of the complex prepared by other methods.

  3. Engineering of Piroxicam Agglomerates by Additives Using Wet Agglomeration Technique

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    Maryam Maghsoodi 1 *

    2016-12-01

    Full Text Available Background: Wet agglomeration is a method wherein the crystals of dispersion are held together in aggregates by small amount of a liquid acting as an intercrystal binder. In present study, in order to study the possible modification of agglomerate structure, low concentrations of additives (0.1-1% were added to binder liquid. Methods: Piroxicam agglomerates were produced by wet agglomeration method by three solvent systems including a good solvent (dimethylformamide or acetone, antisolvent (water and a binder liquid (ethylacetate or isopropylacetate. Span 80, talc, ethylcellulose and Eudragit RS in different concentrations were used as additives. The agglomerates were evaluated for production yield of agglomerates, size, friability and drug release properties. Results: The results showed that formation of agglomerates was possible in presence of span and talc. However, no agglomerates could be obtained with polymers tested (ethylcellulose and Eudragit RS. Talc increased agglomerate size, whereas the obtained agglomerates were more susceptible to breakup. However, using span as opposed to talc resulted in agglomerates with higher strength but smaller particle size. The dissolution tests showed that both additives adversely affected the dissolution rate of piroxicam from the agglomerates. Conclusion: Result of this study suggested that additives even in small amounts played a major role in agglomerate properties.

  4. Clinical trial of osteoarthritis jamu formula compare to piroxicam

    Directory of Open Access Journals (Sweden)

    Danang Ardiyanto

    2016-12-01

    Full Text Available Latar belakang: Indonesia memiliki beberapa ramuan tradisional yang telah digunakan untuk mengurangi nyeri pada osteoarthritis (OA. Namun belum ada bukti yang kuat mengenai khasiat dan keamanan dari ramuan tradisional. Penelitian ini memberikan bukti mengenai khasiat dan keamanan dari satu ramuan tradisional. Metode: Penelitian ini menggunakan metode randomized clinical trial (RCT dengan 123 subyek (pasien selama 28 hari intervensi. Penelitian ini dilakukan pada bulan Maret – Desember 2014 oleh 30 dokter Saintifikasi Jamu di 20 provinsi. Formula jamu dibandingkan dengan piroksikam sebagai kontrol positif. Parameter yang digunakan untuk mengevaluasi khasiat formula jamu dan piroxicam adalah visual analogue score (VAS, pilot geriatric arthritis project (PGAP functional status assessment (FSA, dan Short Form (SF-36. Untuk mengevaluasi keamanan digunakan nilai serum glutamic-oxaloacetic transaminase (SGOT, serum glutamic pyruvic transaminase level (SGPT, blood urea nitrogen (BUN, dan kreatinin. Hasil: Sebanyak 123 pasien yang dibagi menjadi dua kelompok yaitu 63 subyek pada kelompok formula jamu dan 60 subyek pada kelompok piroksikam. Pemberian jamu dapat menurunkan VAS secara bermakna (p<0,05 jika dibandingkan dengan hari ke-0. Nilai FSA kelompok jamu turun secara bermakna (p=0,000 jika dibandingkan dengan nilai di awal intervensi. Formula jamu dapat memperbaiki nilai SF-36 bila dibandingkan dengan hari ke-0. Nilai ketiga parameter antara jamu formula dan piroksikam, jika dibandingkan tidak berbeda bermakna (p>0,05. Kelompok formula jamu menunjukkan nilai SGOT, SGPT, BUN, dan kreatinin dalam ambang normal. Kesimpulan: Penelitian ini menunjukkan bahwa ramuan jamu secara klinis, khasiatnya sebanding dengan piroxicam dan aman setelah intervensi selama 28 hari. Kata kunci: khasiat, keamanan, RCT, ramuan Abstract Background: Indonesian herbs have several formulas which have been used traditionally to reduce pain of osteoarthritis (OA. However, there

  5. Piroxicam and Doxepin—An Alternative to Narcotic Analgesics in Managing Advanced Cancer Pain

    Science.gov (United States)

    Cohn, L.; Machado, Antonio F.; Bier, Robert; Cohn, Marthe

    1988-01-01

    To provide an effective continuum of the relief of severe carcinomatous pain with minimal side reactions, we initiated treatment with piroxicam (60 to 120 mg per day) and doxepin hydrochloride (25 to 225 mg per day). Of 30 patients presenting with severe pain of cancer of various origins, 7 continued to death with piroxicam and doxepin therapy. An additional 17 were successfully treated for 6 to 66 weeks with therapy reported here but, as disease progressed, required supplemental narcotics. The remaining six abandoned the use of piroxicam due to complications of therapy, which ranged from diarrhea to gastric perforation; serious complications were associated with patients' failure to adhere to a prescribed regimen of sucralfate. Therapy with piroxicam and doxepin proved to be safe and efficacious. PMID:3363962

  6. Derivatization of enolic OH of piroxicam: a comparative study on esters and sulfonates

    Energy Technology Data Exchange (ETDEWEB)

    Jayaselli, J.; Cheemala, J. Manila Sagar; Geetha Rani, D.P.; Pal, Sarbani [MNR Post Graduate College, Kukatpally, Hyderabad (India). Dept. of Chemistry]. E-mail: sarbani277@yahoo.com

    2008-07-01

    A number of ester and sulfonate derivatives of piroxicam were prepared via acylation/sulfonation of the enolic OH of piroxicam. All the compounds were evaluated for their chemical stability and cyclooxygenase inhibiting properties. Data suggested that esters could be useful for the development of potential prodrugs. The sulfonate derivatives prepared for the first time were found to be stable. One of them showed a moderately selective COX-2 inhibition over COX-1 and would have lower gastrointestinal side effects than piroxicam due to the masked enolic OH group. A plausible mechanism for the acylation/sulfonation process has been proposed that involves participation of the pyridine moiety of piroxicam. Molecular structure of one of the ester was established for the first time by the crystal structure analysis from X-ray powder data. (author)

  7. Effective method for the detection of piroxicam in human plasma using HPLC.

    Science.gov (United States)

    Calvo, Adriana Maria; Prado, Mariel Tavares de Oliveira; Dionísio, Thiago José; Marques, Maria Paula; Brozoski, Daniel Thomas; Lanchote, Vera Lúcia; Faria, Flávio Augusto Cardoso; Santos, Carlos Ferreira

    2016-05-20

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used by the general population to alleviate inflammation and pain after oral surgeries. Piroxicam is among the most commonly used NSAIDs and excels in controlling pain, swelling, trismus and other common symptoms of inflammation. This study aimed to evaluate different concentrations of piroxicam and its major metabolite, 5'-hydroxypiroxicam, in human plasma samples over time using high performance liquid chromatography (HPLC) after liquid-liquid extraction. Briefly, 10 volunteers participated in this study after approval by the Ethics Committee of Bauru School of Dentistry, Universidade de São Paulo - USP, Brazil. Volunteers received a single dose oral of piroxicam (20 mg) and had blood collected at various times following an established protocol. The methodology of liquid-liquid extraction was effective for determining concentrations of piroxicam in plasma using HPLC in 10 out of 10 volunteers while 5'-hydroxypiroxicam was only detected in 2 out of 10 volunteers.

  8. IN VITRO AND IN VIVO EVALUATION OF PIROXICAM LOADED CERAMIC NANOPARTICLES

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    PAVANI VENGALA

    2016-07-01

    Full Text Available The use of nanotechnology in drug delivery is spreading rapidly. The nanocarriers have been used for the enhanced delivery of a range of drugs. The present study was aimed at investigating the application of ceramic nanoparticles called as aquasomes for the delivery of drug, piroxicam. Piroxicam belongs to oxicam group of NSAID’s, commonly used for the treatment of arthritis. It is a BCS class II drug, with low solubility. There is a need to improve the dissolution property of piroxicam in order to enhance its therapeutic efficacy. Ceramic Nanoparticles were prepared by colloidal precipitation method. The ceramic core was coated with polysaccharide, cellobiose, followed by adsorption of drug. The drug loaded nanoparticles were evaluated for size, entrapment efficiency and drug release profile. The SEM studies indicated that the formed particles were with nanometric dimensions (185 nm. 21% drug loading was observed and more than 95% drug release was observed within 135 min in 0.1N HCl compared with pure drug which released 89% in 90 mins. In vitro dissolution studies indicated that the piroxicam ceramic nanoparticles released the drug in a controlled manner. Anti-nociceptive and anti-inflammatory studies were performed with piroxicam cellobiose aquasomes. Paw edema method was employed for assessing anti-inflammatory effect. The anti-inflammatory activity of aquasome formulation showed quicker effect up to 3 h compared to pure piroxicam.

  9. Comparison of oral versus sublingual piroxicam during postoperative pain management after lower third molar extraction.

    Science.gov (United States)

    Trindade, P A K; Giglio, F P M; Colombini-Ishikiriama, B L; Calvo, A M; Modena, K C S; Ribeiro, D A; Dionísio, T J; Brozoski, D T; Lauris, J R P; Faria, F A C; Santos, C F

    2011-03-01

    In this study, 53 patients received piroxicam, administered orally or sublingually, after undergoing removal of symmetrically positioned lower third molars, during two separate appointments. This study used a randomized, blind, cross-over protocol. Objective and subjective parameters were recorded for comparison of postoperative results for 7 days after surgery. Patients treated with oral or sublingual piroxicam reported low postoperative pain scores. The patients who received piroxicam orally took a similar average amount of analgesic rescue medication compared with patients who received piroxicam sublingually (p>0.05). Patients exhibited similar values for mouth opening measured just before surgery and immediately following suture removal 7 days later (p>0.05), and showed no significant differences between routes of piroxicam administration for swelling control during the second or seventh postoperative days (p>0.05). In summary, pain, trismus and swelling after lower third molar extraction, independent of surgical difficulty, could be controlled by piroxicam 20mg administered orally or sublingually and no significant differences were observed between the route of delivery used in this study.

  10. Solid-state dependent dissolution and oral bioavailability of piroxicam in rats.

    Science.gov (United States)

    Lust, Andres; Laidmäe, Ivo; Palo, Mirja; Meos, Andres; Aaltonen, Jaakko; Veski, Peep; Heinämäki, Jyrki; Kogermann, Karin

    2013-01-23

    The aim of this study was to gain understanding about the effects of different solid-state forms of a poorly water-soluble piroxicam on drug dissolution and oral bioavailability in rats. Three different solid-state forms of piroxicam were studied: anhydrate I (AH), monohydrate (MH), and amorphous form in solid dispersion (SD). In addition, the effect of a new polymeric excipient Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) on oral bioavailability of piroxicam was investigated. Significant differences in the dissolution and oral bioavailability were found between the solid-state forms of piroxicam. Amorphous piroxicam in SD showed the fastest dissolution in vitro and a solid-state transformation to MH in the dissolution medium. Despite the presence of solid-state transformation, SD exhibited the highest rate and extent of oral absorption in rats. Oral bioavailability of other two solid-state forms decreased in the order AH and MH. The use of Soluplus® was found to enhance the dissolution and oral bioavailability of piroxicam in rats. The present study shows the importance of solid-state form selection for oral bioavailability of a poorly water-soluble drug.

  11. Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice.

    Science.gov (United States)

    C, Jadiswami; H M, Megha; Dhadde, Shivsharan B; Durg, Sharanbasappa; Potadar, Pandharinath P; B S, Thippeswamy; V P, Veerapur

    2014-12-01

    3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington's disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions.

  12. Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma.

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    Alfonso Baldi

    Full Text Available BACKGROUND: Malignant mesothelioma (MM is a rare, highly aggressive tumor, associated to asbestos exposure. To date no chemotherapy regimen for MM has proven to be definitively curative, and new therapies for MM treatment need to be developed. We have previously shown in vivo that piroxicam/cisplatin combined treatment in MM, specifically acts on cell cycle regulation triggering apoptosis, with survival increase. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed, at molecular level, the apoptotic increase caused by piroxicam/cisplatin treatment in MM cell lines. By means of genome wide analyses, we analyzed transcriptional gene deregulation both after the single piroxicam or cisplatin and the combined treatment. Here we show that apoptotic increase following combined treatment is mediated by p21, since apoptotic increase in piroxicam/cisplatin combined treatment is abolished upon p21 silencing. CONCLUSIONS/SIGNIFICANCE: Piroxicam/cisplatin combined treatment determines an apoptosis increase in MM cells, which is dependent on the p21 expression. The results provided suggest that piroxicam/cisplatin combination might be tested in clinical settings in tumor specimens that express p21.

  13. Khaya senegalensis inhibits piroxicam mediated gastro-toxicity in wistar rats

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    Fatima Nnawodu Ishaq

    2014-11-01

    Full Text Available Objective:The purpose of this study was to investigate the effects of piroxicam co-administration with ethanolic stem-bark extract of Khaya senegalensis on biomarkers of oxidative stress and gastro-toxicity in Wistar rats. Materials and Methods: Thirty healthy male and female Albino Wistar rats (190-220 g were grouped into six (n = 5 with designated treatments including: Normal saline, piroxicam (20 mg/kg, extract (200 and 400 mg/kg alone and both doses of the extract co-administered with piroxicam. The drugs were administered orally to all the rats for fourteen consecutive days and on the fifteenth day, they were euthanized with chloroform inhalation. Blood samples and the stomachs were isolated for evaluation of the oxidative stress biomarkers and gastro integrity, respectively. Results: The results of the study revealed that the levels of oxidative stress markers didn’t differ significantly between the groups receiving the extract alone, the extract in combination or piroxicam alone. Gross and histological observations of the stomach showed gastric mucosal changes and mild atrophic lesions in the piroxicam group only. Conclusion: This study illustrates the interaction of Khaya senegalensis and piroxicam results in the gastro-protective beneficial effects. The extract’s outcome on various prostaglandin levels and synthesis is being considered towards possible elucidation regarding the exact mechanism of cytoprotection.  

  14. Piroxicam and laser phototherapy in the treatment of TMJ arthralgia: a double-blind randomised controlled trial.

    Science.gov (United States)

    de Carli, M L; Guerra, M B; Nunes, T B; di Matteo, R C; de Luca, C E P; Aranha, A C C; Bolzan, M C; Witzel, A L

    2013-03-01

    This study aimed to evaluate the efficacy of piroxicam associated with low-level laser therapy compared with single therapies in 32 patients presenting temporomandibular joint arthralgia in a random and double-blind research design. The sample, divided into laser + piroxicam, laser + placebo piroxicam and placebo laser + piroxicam groups, was submitted to the treatment with infrared laser (830 nm, 100 mW, 28 s, 100 J cm(-2) ) at 10 temporomandibular joint and muscle points on each side during four sessions concomitant to take one capsule a day of piroxicam 20 mg during 10 days. The treatment was evaluated throughout four sessions and 30 days follow-up through visual analogue scale (VAS), maximum mouth opening and joint and muscle (temporal and masseter) pain on palpation. The results showed that all the study groups had a significant improvement in the VAS scores (P Piroxicam was effective in the reduction of joint and muscle pain on palpation (P piroxicam was not more effective than single therapies in the treatment of temporomandibular joint arthralgia. The use of piroxicam was more effective in the following 30 days.

  15. Clinical evaluation of piroxicam-FDDF and azithromycin in the prevention of complications associated with impacted lower third molar extraction.

    Science.gov (United States)

    Graziani, F; Corsi, L; Fornai, M; Antonioli, L; Tonelli, M; Cei, S; Colucci, R; Blandizzi, C; Gabriele, M; Del Tacca, M

    2005-12-01

    Combined treatments with non-steroidal anti-inflammatory drugs and antibiotics may offer significant benefits in the prevention of pain and infections associated with oral surgery. In this study, piroxicam and azithromycin were administered to patients undergoing dental extraction to examine the efficacy of piroxicam in the prevention of post-operative pain and inflammatory complications, either in the absence or in the presence of a concomitant antibiotic treatment. Thirty patients were randomly assigned to three groups and treated for 3 days, before impacted lower third molar removal, as follows: (1) sublingual piroxicam-FDDF (fast dissolving dosage formulation) 20 mg/day; (2) oral azithromycin 500 mg/day; (3) piroxicam-FDDF 20 mg/day plus azithromycin 500 mg/day. Oral acetaminophen (500 mg tablets) was allowed as rescue analgesic medication. Pain intensity was evaluated on a 100-mm visual-analogue scale after dental extraction (day 1), and at days 2, 3, 7 after surgery. Edema and trismus were estimated at days 2 and 7. At days 1 and 2, pain intensity was significantly lower in patients treated with piroxicam-FDDF, either alone (p operative period, piroxicam-FDDF effectively counteracts post-surgical pain and inflammatory reactions in oral tissues. Upon combined treatment with piroxicam-FDDF and azithromycin, the macrolide antibiotic may reduce the influence of piroxicam on post-operative inflammation, without affecting its beneficial effect on surgical pain.

  16. Piroxicam-mediated modulatory action of 5-hydroxytryptamine serves as a “brake” on neuronal excitability in ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Pallab Bhattacharya; Anand Kumar Pandey; Sudip Paul; Ranjana Patnaik

    2015-01-01

    Our previous studies indicated an increase in extracellularγ-aminobutyric acid (GABA) in rodent’s ischemic brain after Piroxicam administration, leading to alleviation of glutamate me-diated excitotoxicity through activation of type A GABA receptor (GABAA). This study was to investigate if GABAA activation by Piroxicam affects extracellular 5-hydroxytryptamine or not. High performance liquid chromatography revealed that there was a signiifcant decrease in ex-tracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum in Piroxicam pre-treated rat brains. This suggests a probable role of Piroxicam in reducing extracellular 5-hy-droxytryptamine release in ischemic cerebral cortex and striatum possibly due to the GABAA activation by Piroxicam.

  17. The effect of physico-chemical properties of the drug on the pharmaceutical availability of piroxicam from pellets.

    Science.gov (United States)

    Pieszczek, Barbara; Jachowicz, Renata

    2010-06-01

    The aim of this study was to develop the formulation of pellets with solid dispersions of piroxicam, and determine the effect of physico-chemical properties of the drug on pharmaceutical availability from solid dispersions and pellets. Two types of piroxicam, varying in crystal size, were used in this study. Presence of the amorphous form in solid dispersions depended on the method of their formulation, and type of piroxicam used. Based on the results of piroxicam release rate from pellets, it was established that the extrusion and spheronization process caused change in the drug release profile in comparison to powder systems, because during the pelletization process, the amorphous form of the piroxicam present in the solid dispersion recrystallizes, and a low-solubility type forms. Better results were obtained using the method, where microcrystalline cellulose cores were coated with solid dispersion.

  18. Development and characterization of solid dispersion of piroxicam for improvement of dissolution rate using hydrophilic carriers

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    Mohammad Barzegar-jalali

    2014-09-01

    Full Text Available Introduction: The main objective of this study was preparation and characterization of solid dispersion of piroxicam to enhance its dissolution rate. Methods: Solid dispersion formulations with different carriers including crospovidone, microcrystalline cellulose and Elaeagnus angustifolia fruit powder and with different drug: carrier ratios were prepared employing cogrinding method. Dissolution study of the piroxicam powders, physical mixtures and solid dispersions was performed in simulated gastric fluid and simulated intestinal fluid using USP Apparatus type II. The physical characterization of formulations were analyzed using powder X ray diffraction (PXRD, particle size analyzer and differential scanning calorimetry (DSC. Interactions between the drug and carriers were evaluated by Fourier transform infrared (FT-IR spectroscopic method. Results: It was revealed that all of three carriers increase the dissolution rate of piroxicam from physical mixtures and especially in solid dispersions compared to piroxicam pure and treated powders. PXRD and DSC results were confirmed the reduction of crystalline form of piroxicam. FT-IR analysis did not show any physicochemical interaction between drug and carriers in the solid dispersion formulations. Conclusion: Dissolution rate was dependent on the type and ratio of drug: carrier as well as pH of dissolution medium. Dissolution data of formulations were fitted well in to the linear Weibull as well as non-linear logistic and a suggested models.

  19. (14) N nuclear quadrupole resonance study of piroxicam: confirmation of new polymorphic form V.

    Science.gov (United States)

    Lavrič, Zoran; Pirnat, Janez; Lužnik, Janko; Puc, Uroš; Trontelj, Zvonko; Srčič, Stane

    2015-06-01

    A new polymorphic crystal form of piroxicam was discovered while preparing crystalline samples of piroxicam for (14) N nuclear quadrupole resonance (NQR) analysis. The new crystal form, designated as V, was prepared by evaporative recrystallization from dichloromethane. Three known polymorphic forms (I, II, and III) were also prepared. Our aim was to apply (14) N NQR to characterize the new polymorphic form of piroxicam and compare the results with those of the other known polymorphic forms. Additional analytical methods used for characterization were X-ray powder diffraction (XRPD), thermal analysis, and vibrational spectroscopy. For the first time, a complete set of nine characteristic (14) N NQR frequencies was found for each prepared polymorph of piroxicam. The consistent set of measured frequencies and calculated characteristic quadrupole parameters found for the new polymorphic form V is a convincing evidence that we are dealing with a new form. The already known piroxicam polymorphic forms were characterized similarly. The XRPD results were in accordance with the conclusions of (14) N NQR analysis. The performed study clearly demonstrates a strong potential of (14) N NQR method to be applied as a highly discriminative spectroscopic analytical tool to characterize polymorphic forms.

  20. Application of 14N NQR to the study of piroxicam polymorphism.

    Science.gov (United States)

    Lavrič, Zoran; Pirnat, Janez; Lužnik, Janko; Seliger, Janez; Zagar, Veselko; Trontelj, Zvonko; Srčič, Stane

    2010-12-01

    A study was conducted to test the capability of the (14)N nuclear quadrupole resonance (NQR) method to discriminate qualitatively and quantitatively among different forms of piroxicam. Samples of commercial piroxicam form I and its monohydrate were obtained on the local market. Additionally, samples of form I and II were prepared by recrystallization in 1,2-dichloroethane and ethanol, respectively. DSC and FT-IR were employed as reference methods. A (14)N NQR spectrometer was used to measure samples of different forms and mixtures of piroxicam at 2587 and 3439  kHz. DSC and FT-IR clearly confirmed differences between the different piroxicam forms. Measurements of (14)N NQR signals of different forms of piroxicam at 2587  kHz detected only spectral peaks of form I. The dependence of (14)N NQR signal intensity on the concentration of form I in mixtures with the monohydrate showed a clear linear relationship at both measured frequencies, though the scattering of data was greater at 3439  kHz due to the lower S/N ratio. The (14)N NQR method has the potential to become an additional and important spectroscopic tool in the study of solid-state forms, not only of pure active pharmaceutical ingredients or excipients, but also of their mixtures. This ability lends the method to a possible successful utilization at different levels of pharmaceutical manufacturing and product quality control.

  1. Piroxicam loaded alginate beads obtained by prilling/microwave tandem technique: morphology and drug release.

    Science.gov (United States)

    Aquino, Rita P; Auriemma, Giulia; d'Amore, Matteo; D'Ursi, Anna Maria; Mencherini, Teresa; Del Gaudio, Pasquale

    2012-07-01

    This paper presents a tandem technique, based on the combination of prilling and microwave (MW) assisted treatments, to produce biodegradable alginate carriers of piroxicam with different drug controlled release behaviours. Results showed that alginate/piroxicam beads demonstrated high encapsulation efficiency and very narrow dimensional distribution. Beads dried by MW retained shape and size distribution of the hydrated particles while drying rate was strongly increased compared to convective drying processes. Moreover, different MW irradiation regimes promoted interactions between the drug and alginate matrix, affected drug polymorphism as well as inner and surface matrix structure leading to different piroxicam release profiles. High level MW irradiation led to beads with highly porous and swellable matrix able to release piroxicam in few minutes in the intestine while convective drying produced gastro-resistant beads that exhibit sustained piroxicam release (total release in 5.5h) in intestinal environment. On these results the tandem technique prilling/MW irradiation appears to be promising to obtain alginate carrier with tailored NSAIDs release depending on drug characteristics and MW irradiation.

  2. Evaluation of piroxicam-beta-cyclodextrin as a preemptive analgesic in functional endoscopic sinus surgery.

    Science.gov (United States)

    Keleş, G T; Topçu, I; Ekici, Z; Yentür, A

    2010-08-01

    The preemptive analgesic efficacy and adverse effects of preoperatively administered piroxicam-beta-cyclodextrin for post-endoscopic sinus surgery pain was determined in a prospective, double-blind, randomized, clinical study. Seventy-five American Society of Anesthesiologists status I-II patients, aged 18-65 years, were divided into three groups with similar demographic characteristics: group 1 received 20 mg piroxicam-beta-cyclodextrin, group 2 received 40 mg piroxicam-beta-cyclodextrin and group 3 received placebo orally before induction of general anesthesia. A blinded observer recorded the incidence and severity of pain at admission to the post-anesthesia care unit (PACU), at 15, 30, and 45 min in the PACU, and 1, 2, 4, 6, and 24 h postoperatively. All patients received patient-controlled morphine analgesia during the postoperative period and consumption was recorded for 24 h. During the PACU period, mean visual analogue scale values were significantly lower in groups 1 and 2 compared to group 3 (P piroxicam-beta-cyclodextrin effectively reduced analgesic consumption, and 40 mg of the drug was more effective than 20 mg piroxicam-beta-cyclodextrin without side effects during the postoperative period.

  3. Protective value of piroxicam on the enhanced inflammatory response after whole body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    el-Ghazaly, M.; Saleh, S.; Kenawy, S.; Roushdy, H.M.; Khayyal, M.T.

    1986-06-01

    The anti-inflammatory activity of piroxicam was assessed after whole body irradiation in rats. Two models of inflammation, the carrageenan-induced edema and the adjuvant-induced arthritis in rats have been utilised. Piroxicam at doses of 1, 5 and 10 mg kg-1 i.p. was effective in inhibiting the paw edema produced in both models of inflammation. The inflammatory response in irradiated was significantly higher than that produced in normal animals and was dependent on the radiation dose level used (0.5-2 Gy). The effect of piroxicam on the late inflammatory response produced by exposure to 2 Gy was studied by measuring the carrageenan-induced edema 4 h after irradiation and on the third and seventh day thereafter. The increase in paw volume was significantly suppressed in animals receiving the drug. Administration of piroxicam (5 mg kg-1) one hour before irradiation of animals at 0.5 Gy, produced inhibition to the exaggerated inflammatory response in irradiated animals. This suggests that piroxicam possibly owes its protective value to prevention of the increase in cellular permeability induced by radiation. Alternatively, the drug may exert this effect by inhibiting PG synthesis, thereby reducing their potentiating influence on the other mediators of inflammation. Furthermore, the inhibition of lysosomal enzyme release possibly induced by the drug may contribute to the probable reduction in the release of inflammatory mediators.

  4. Piroxicam immediate release formulations: A fasting randomized open-label crossover bioequivalence study in healthy volunteers.

    Science.gov (United States)

    Helmy, Sally A; El-Bedaiwy, Heba M

    2014-11-01

    Piroxicam is a NSAID with analgesic and antipyretic properties, used for the treatment of rheumatoid diseases. The aim of this study was to evaluate the bioequivalence of two brands of piroxicam capsules (20 mg) in 24 Egyptian volunteers. The in vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2-period, 2-sequence, crossover study with a washout period of 3 weeks. Under fasting conditions, 24 healthy male volunteers were randomly selected to receive a single oral dose of one capsule (20 mg) of either test or reference product. Plasma samples were obtained over a 144-hour interval and analyzed for piroxicam by HPLC with UV detection. The pharmacokinetic parameters Cmax , tmax , AUC0-t , AUC0-∞ , Vd /F, Cl/F, and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of Cmax , AUC0-t , and AUC0-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, the two piroxicam formulations were considered bioequivalent, based on the rate and extent of absorption. No adverse events occurred or were reported after a single 20-mg piroxicam and both formulations were well-tolerated.

  5. Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages

    Directory of Open Access Journals (Sweden)

    Chiong HS

    2013-03-01

    Full Text Available Hoe Siong Chiong,1 Yoke Keong Yong,1 Zuraini Ahmad,1 Mohd Roslan Sulaiman,1 Zainul Amiruddin Zakaria,1 Kah Hay Yuen,2 Muhammad Nazrul Hakim1,31Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 2School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, Malaysia; 3Sports Academy, Universiti Putra Malaysia, Serdang, MalaysiaBackground: Liposomal drug delivery systems, a promising lipid-based nanoparticle technology, have been known to play significant roles in improving the safety and efficacy of an encapsulated drug.Methods: Liposomes, prepared using an optimized proliposome method, were used in the present work to encapsulate piroxicam, a widely prescribed nonsteroidal anti-inflammatory drug. The cytotoxic effects as well as the in vitro efficacy in regulation of inflammatory responses by free-form piroxicam and liposome-encapsulated piroxicam were evaluated using a lipopolysaccharide-sensitive macrophage cell line, RAW 264.7.Results: Cells treated with liposome-encapsulated piroxicam demonstrated higher cell viabilities than those treated with free-form piroxicam. In addition, the liposomal piroxicam formulation resulted in statistically stronger inhibition of pro-inflammatory mediators (ie, nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2 than piroxicam at an equivalent dose. The liposome-encapsulated piroxicam also caused statistically significant production of interleukin-10, an anti-inflammatory cytokine.Conclusion: This study affirms the potential of a liposomal piroxicam formulation in reducing cytotoxicity and enhancing anti-inflammatory responses in vitro.Keywords: liposomes, nitric oxide, cytokines, prostaglandin E2, interleukin-1β, piroxicam

  6. Effect of piroxicam, metamizol, and S-adenosylmethionine in a murine model of experimental trichomoniasis

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    Nogal-Ruiz J.J.

    2005-03-01

    Full Text Available Biological effects of piroxicam, metamizol, and S-adenosylmethionine (S-AMET have been tested in NMRI mice infected intraperitoneally with Trichomonas vaginalis. An intraperitoneal treatment during ten preinfection days with piroxicam (10 mg/Kg/day, or metamizol (275 mg/Kg/day, but not with S-AMET (17 mg/Kg/day induced a significant decrease of abdominal lesions and mortality, assessed by means of a pathogenicity index. The trichomonicidal activity of piroxicam, metamizol, and S-AMET was tested in vitro at the concentration of 300 μM, but found ineffective. These assays have shown the usefulness of the experimental trichomoniasis model for the study of the immunomodulating activity of synthetic drugs.

  7. Spectrophotometric and potentiometric determination of piroxicam and tenoxicam in pharmaceutical preparations.

    Science.gov (United States)

    El-Ries, Mohamed A; Mohamed, Gehad; Khalil, Shaeban; El-Shall, Manal

    2003-01-01

    Two simple and accurate methods are described for the determination of piroxicam and tenoxicam in their pharmaceutical preparations. The spectrophotometric method involves the oxidation of these drugs with potassium iodate in acid medium with the liberation of iodine and subsequent extraction with cyclohexane followed by measuring the absorbance at lambda=522 nm. Beer's law is obeyed in the concentration range of 0.05-1.1 and 0.05-0.6 mg x ml(-1) for piroxicam and tenoxicam, respectively. The apparent molar absorptivities of the resulting coloured products are found to be 2.7 x 10(3) and 2.5 x 10(3) l mol(-1) x cm(-1), whereas Sandell sensitivities are 0.012 and 0.013 g x cm(-2) for piroxicam and tenoxicam, respectively. The potentiometric method involves the direct titration of both drugs with N-bromosuccinimide in acid medium and the end point is determined potentiometrically using platinum indicator electrode. Piroxicam and tenoxicam can be determined quantitatively in the concentration range of 0.33-3.37 and 0.33-4.08 mg x ml(-1) for tenoxicam and piroxicam, respectively. The standard deviation and relative standard deviation values are found to be ranged from 0.05-0.07 and 0.37-0.98% and 0.025-0.078 and 0.25-1.2% for tenoxicam and piroxicam, respectively. The two methods are accurate within +/-1.0%. Optimum conditions affecting both methods are studied. The proposed methods are applied for the determination of the drugs in pure form and in commercial pharmaceutical preparations.

  8. Synthesis of new piroxicam derivatives and their influence on lipid bilayers.

    Science.gov (United States)

    Szczęśniak-Sięga, Berenika; Maniewska, Jadwiga; Poła, Andrzej; Środa-Pomianek, Kamila; Malinka, Wiesław; Michalak, Krystyna

    2014-01-01

    A novel series of potentially biologically active 1,2-benzothiazine 1,1-dioxides--analogs of piroxicam (a recognized non-steroidal anti-inflammatory drug) were synthesized from commercially available saccharin. All of the synthesized compounds were subjected to preliminary evaluation for their ability to interact with lipid bilayers. The influence of the new derivatives of piroxicam on liposomes made of EYPC was investigated by fluorescence spectroscopy with two fluorescent probes--Laurdan and Prodan. All the studied compounds showed an interaction with model membranes.

  9. Characterisation of enterocolitis in the piroxicam-accelerated interleukin-10 knock out mouse

    DEFF Research Database (Denmark)

    Holgersen, Kristine; Kvist, Peter Helding; Markholst, Helle;

    2014-01-01

    Background: In inflammatory bowel disease a defective mucosal barrier, a dysregulated immune response and an excessive reactivity against the gut microbiota are assumed to cause a breakdown of the intestinal homeostasis and lead to chronic inflammation. Piroxicam treatment is a method for induction...... of colitis in IL-10 k.o. mice, which integrates a dysfunction of both the intestinal barrier and the immune system. However, the translational value of this model has not been thoroughly clarified. Aim: To characterise the piroxicam-accelerated colitis (PAC) IL-10 k.o. model with respect to clinical features...

  10. Design, Synthesis, Antinociceptive and Anti-Inflammatory Activities of Novel Piroxicam Analogues

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    Eliezer J. Barreiro

    2012-11-01

    Full Text Available In this paper we report the design, synthesis, antinociceptive and anti-inflammatory activities of a series of benzothiazine N-acylhydrazones 14a–h, planned by structural modification of piroxicam (1, a non steroidal anti-inflammatory drug. Among the synthesized analogues, compounds 14f (LASSBio-1637 and 14g (LASSBio-1639 were identified as novel antinociceptive and anti-inflammatory prototypes, active by oral administration, acting by a mechanism of action that seems to be different from that of piroxicam, since they were inactive as an inhibitor of cyclooxygenase (COX-1 and COX-2 at concentrations of 10 mM.

  11. The interaction of new piroxicam analogues with lipid bilayers--a calorimetric and fluorescence spectroscopic study.

    Science.gov (United States)

    Maniewska, Jadwiga; Szczęśniak-Sięga, Berenika; Poła, Andrzej; Sroda-Pomianek, Kamila; Malinka, Wiesław; Michalak, Krystyna

    2014-01-01

    The purpose of the present paper was to assess the ability of new piroxicam analogues to interact with the lipid bilayers. The results of calorimetric and fluorescence spectroscopic experiments of two new synthesized analogues of piroxicam, named PR17 and PR18 on the phase behavior of phospholipid bilayers and fluorescence quenching of fluorescent probes (Laurdan and Prodan), which molecular location within membranes is known with certainty, are shown in present work. The presented results revealed that, depending on the details of chemical structure, the studied compounds penetrated the lipid bilayers.

  12. Design, synthesis, antinociceptive and anti-inflammatory activities of novel piroxicam analogues.

    Science.gov (United States)

    de Miranda, Amanda Silva; Bispo Júnior, Walfrido; da Silva, Yolanda Karla Cupertino; Alexandre-Moreira, Magna Suzana; Castro, Rosane de Paula; Sabino, José Ricardo; Lião, Luciano Morais; Lima, Lídia Moreira; Barreiro, Eliezer J

    2012-11-28

    In this paper we report the design, synthesis, antinociceptive and anti-inflammatory activities of a series of benzothiazine N-acylhydrazones 14a–h, planned by structural modification of piroxicam (1), a non steroidal anti-inflammatory drug. Among the synthesized analogues, compounds 14f (LASSBio-1637) and 14g (LASSBio-1639) were identified as novel antinociceptive and anti-inflammatory prototypes, active by oral administration, acting by a mechanism of action that seems to be different from that of piroxicam, since they were inactive as an inhibitor of cyclooxygenase (COX-1 and COX-2) at concentrations of 10 mM.

  13. A theoretical and spectroscopic study of conformational structures of piroxicam

    Science.gov (United States)

    Souza, Kely Ferreira de; Martins, José A.; Pessine, Francisco B. T.; Custodio, Rogério

    2010-02-01

    Piroxicam (PRX) has been widely studied in an attempt to elucidate the causes and mechanisms of its side effects, mainly the photo-toxicity. In this paper fluorescence spectra in non-protic solvents and different polarities were carried out along with theoretical calculations. Preliminary potential surfaces of the keto and enol forms were obtained at AM1 level of theory providing the most stable conformers, which had their structure re-optimized through the B3LYP/CEP-31G(d,p) method. From the optimized structures, the electronic spectra were calculated using the TD-DFT method in vacuum and including the solvent effect through the PCM method and a single water molecule near PRX. A new potential surface was constructed to the enol tautomer at DFT level and the most stable conformers were submitted to the QST2 calculations. The experimental data showed that in apolar media, the solution fluorescence is raised. Based on conformational analysis for the two tautomers, keto and enol, the results indicated that the PRX-enol is the main tautomer related to the drug fluorescence, which is reinforced by the spectra results, as well as the interconvertion barrier obtained from the QST2 calculations. The results suggest that the PRX one of the enol conformers presents great possibility of involvement in the photo-toxicity mechanisms.

  14. DEVELOPMENT AND EVALUATION OF PIROXICAM LOADED BIOPOLYMER BASED TRANSDERMAL FILM

    Directory of Open Access Journals (Sweden)

    Kulkarni Parthasarathi Keshavarao

    2011-11-01

    Full Text Available The aim of the present study was to formulate biopolymer based transdermal film loaded with Piroxicam (PX. Transdermal films were prepared by using sodium locust bean gum (LBG and Sodium alginate (SA as biopolymers by varying the blend ratios by solution casting method. The drug loaded membranes were evaluated for thickness, tensile behaviours, content uniformity; transdermal permeation of PX through rat abdominal skin was determined by Franz diffusion cell. In vitro skin permeation profile of optimized formulation was compared with that of PX conventional gel. Carrageen induced rat paw edema model was used to investigate the in vivo performances. Menthol (3% and glycerin (3% are used as permeation enhancer and plasticizer, respectively. PX was found to be compatible and stable with the prepared formulation as confirmed by Fourier transform infrared spectroscopy (FTIR and Differential Scanning Calorimetric (DSC, studies. In-vitro release studies revels effectiveness after 24 h when compared with the conventional gel. The film does not show any signs of edema, erythema or ulceration. From the in-vitro skin permeation and anti inflammatory activity data it can be concluded that the developed optimized formulation (F3 has good potential to achieve the transdermal drug delivery of PX for effective therapy.

  15. Study of surface activity of piroxicam at the interface of palm oil esters and various aqueous phases.

    Science.gov (United States)

    Abdulkarim, Muthanna Fawzy; Abdullah, Ghassan Zuhair; Chitneni, Mallikarjun; Yam, Mun Fei; Mahdi, Elrashid Saleh; Salman, Ibrahim Muhammad; Ameer, Omar Ziad; Sattar, Munavvar Abdul; Basri, Mahiran; Noor, Azmin Mohd

    2012-04-01

    The surface activity of some non-steroidal anti-inflammatory agents like ibuprofen was investigated extensively. This fact has attracted the researchers to extend this behavior to other agents like piroxicam. Piroxicam molecules are expected to orient at the interface of oil and aqueous phase. The aim of this study was, firstly, to assess the surface and interfacial tension behaviour of newly synthesised palm oil esters and various pH phosphate buffers. Furthermore, the surface and interfacial tension activity of piroxicam was studied. All the measurements of surface and interfacial tension were made using the tensiometer. The study revealed that piroxicam has no effect on surface tension values of all pH phosphate buffers and palm oil esters. Similarly, various concentrations of piroxicam did not affect the interfacial tensions between the oil phase and the buffer phases. Accordingly, the interfacial tension values of all mixtures of oil and phosphate buffers were considerably high which indicates the immiscibility. It could be concluded that piroxicam has no surface activity. Additionally, there is no surface pressure activity of piroxicam at the interface of plam oil esters and phosphate buffers in the presence of Tweens and Spans.

  16. Amorphous solid dispersions of piroxicam and Soluplus(®): Qualitative and quantitative analysis of piroxicam recrystallization during storage.

    Science.gov (United States)

    Lust, Andres; Strachan, Clare J; Veski, Peep; Aaltonen, Jaakko; Heinämäki, Jyrki; Yliruusi, Jouko; Kogermann, Karin

    2015-01-01

    The conversion of active pharmaceutical ingredient (API) from amorphous to crystalline form is the primary stability issue in formulating amorphous solid dispersions (SDs). The aim of the present study was to carry out qualitative and quantitative analysis of the physical solid-state stability of the SDs of poorly water-soluble piroxicam (PRX) and polyvinyl caprolactam-polyvinyl acetate-polyethylene-glycol graft copolymer (Soluplus(®)). The SDs were prepared by a solvent evaporation method and stored for six months at 0% RH/6 °C, 0% RH/25 °C, 40% RH/25 °C and 75% RH/25 °C. Fourier transform infrared spectroscopy equipped with attenuated total reflection accessory (ATR-FTIR) and Raman spectroscopy were used for characterizing the physical solid-state changes and drug-polymer interactions. The principal component analysis (PCA) and multivariate curve resolution alternating least squares (MCR-ALS) were used for the qualitative and quantitative analysis of Raman spectra collected during storage. When stored at 0% RH/6 °C and at 0% RH/25 °C, PRX in SDs remained in an amorphous form since no recrystallization was observed by ATR-FTIR and Raman spectroscopy. Raman spectroscopy coupled with PCA and MCR-ALS and ATR-FTIR spectroscopy enabled to detect the recrystallization of amorphous PRX in the samples stored at higher humidity.

  17. Crystal structure of a 2:1 piroxicam-gentisic acid co-crystal featuring neutral and zwitterionic piroxicam mol-ecules.

    Science.gov (United States)

    Horstman, Elizabeth M; Bertke, Jeffery A; Woods, Toby J; Kenis, Paul J A

    2016-12-01

    A new 2:1 co-crystal of piroxicam and gentisic acid [systematic name: 4-hy-droxy-1,1-dioxo-N-(pyridin-2-yl)-2H-1λ(6),2-benzo-thia-zine-3-carboxamide-2-(4-oxido-1,1-dioxo-2H-1λ(6),2-benzo-thia-zine-3-amido)-pyridin-1-ium-2,5-di-hydroxy-benzoic acid, 2C15H13N3O4S·C7H6O4] has been synthesized using a microfluidic platform and initially identified using Raman spectroscopy. In the co-crystal, one piroxicam mol-ecule is in its neutral form and an intra-molecular O-H⋯O hydrogen bond is observed. The other piroxicam mol-ecule is zwitterionic (proton transfer from the OH group to the pyridine N atom) and two intra-molecular N-H⋯O hydrogen bonds occur. The gentisic acid mol-ecule shows whole-mol-ecule disorder over two sets of sites in a 0.809 (2):0.191 (2) ratio. In the crystal, extensive hydrogen bonding between the components forms layers propagating in the ab plane.

  18. Effect of virgin olive oil versus piroxicam phonophoresis on exercise-induced anterior knee pain

    Directory of Open Access Journals (Sweden)

    Babak Nakhostin-Roohi

    2016-08-01

    Full Text Available Objective: The main purpose of this study was to evaluate the effects of virgin olive oil phonophoresis on female athletes' anterior knee pain (AKP. Materials and Methods: A double blinded randomized clinical trial was conducted. Ninety-three female athletes suffering from AKP voluntarily participated in this study. Patients were randomly assigned into olive oil (n=31, piroxicam (n=31 or base gel phonophoresis (n=31 groups. At the baseline visit, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC questionnaire was filled by subjects who were then treated with olive oil, piroxicam or pure phonophoresis for 12 sessions. After 6 and 12 sessions of physiotherapy, subjects filled the questionnaire again. Main outcomes were significant improvement in pain, stiffness, physical function, and total WOMAC scores. Results: Although, there was a significant reduction in symptoms of AKP at the end of the therapy in all groups (p< 0.05, but in olive oil group, this improvement was seen after 6 sessions of treatment (p< 0.001. A significant difference between olive oil group and piroxicam and/or phonophoresis group was observed after 6 sessions of therapy (p< 0.05. Conclusion: It could be proposed that phonophoresis with virgin olive oil is as effective as piroxicam gel on lowering WOMAC scores of AKP in female athletes and also has several beneficial properties including faster effect and shorter duration of therapy. The exact mechanism of beneficial action of virgin olive oil on AKP is not clear and requires further studies.

  19. Kinetics of piroxicam release from low-methylated pectin/zein hydrogel microspheres

    Science.gov (United States)

    The kinetics of a model drug (piroxicam) release from pectin/zein hydrogel microspheres was studied under conditions simulating the gastrointestinal tract. It is established that the rate-limiting step in the release mechanism is drug diffusion out of the microspheres rather than its dissolution. ...

  20. Tautomeric transformations of piroxicam in solution: a combined experimental and theoretical study

    DEFF Research Database (Denmark)

    Ivanova, D; Deneva, V; Nedeltcheva, D

    2015-01-01

    Piroxicam tautomerism was studied in solution by using UV-Vis spectroscopy, NMR measurements and advanced chemometrics. It has been found that in ethanol and DMSO the enol-amide tautomer is present mainly as a sandwich type dimer. The addition of water leads to distortion of the aggregate...

  1. Risk factors for treatment-related adverse events in cancer-bearing dogs receiving piroxicam.

    Science.gov (United States)

    Eichstadt, L R; Moore, G E; Childress, M O

    2016-10-06

    Piroxicam has antitumour effects in dogs with cancer, although side effects may limit its use. The purpose of this study was to retrospectively identify factors predisposing cancer-bearing dogs to adverse events (AEs) following piroxicam therapy. Medical records of dogs presented to the Purdue Veterinary Teaching Hospital between 2005 and 2015 were reviewed, and 137 dogs met the criteria for study inclusion. Toxic effects of piroxicam in these dogs were graded according to an established system. Multivariate logistic regression was used to estimate the extent to which certain factors affected the risk for AEs. Age [odds ratio (OR) 1.250, P = 0.009; 95% confidence interval (CI) 1.057-1.479] and concurrent use of gastroprotectant medications (OR 2.612, P = 0.025; 95% CI 1.127-6.056) significantly increased the risk for gastrointestinal AEs. The results of this study may help inform the risk versus benefit calculation for clinicians considering the use of piroxicam to treat dogs with cancer.

  2. Role of hydroxypropylmethylcellulose (HPMC 4000 in the protection of the polymorphs of Piroxicam extended release tablets

    Directory of Open Access Journals (Sweden)

    A. Merah

    2017-02-01

    The physico-chemical tests and the dissolution profiles of polymorphs and tablets showed that the metolose incorporated in the tablets at a rate equivalent to 5% could possibly act doubly; initially by protecting the piroxicam polymorphism transition (form II during compression, then modulating its in vitro release (extended release.

  3. Crystallization and disorder of the polytypic α1 and α2 polymorphs of piroxicam

    DEFF Research Database (Denmark)

    Upadhyay, Pratik Pankaj; Bond, Andrew

    2015-01-01

    Polymorphism of the active pharmaceutical ingredient piroxicam, C15H13N3O4S, is investigated with an aim to clarify the identity and crystallization conditions of the α1 and α2 polymorphs. The structures are polytypic, containing identical 2-dimensional layers, with different symmetry relationships...

  4. The Effects of Piroxicam and Deracoxib on Canine Mammary Tumour Cell Line

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    Fulya Üstün Alkan

    2012-01-01

    Full Text Available Cyclooxygenase (COX inhibitors, already widely used for the treatment of pain and inflammation, are considered as promising compounds for the prevention and treatment of neoplasia. The aim of our study was to determine the direct antiproliferative effects of nonsteroidal anti-inflammatory drugs (NSAIDs, piroxicam and deracoxib, at a variety of concentrations as both single and combined treatments on canine mammary carcinoma cell line CMT-U27 and to understand the mechanisms of cell death. MTT assay was performed to determine cell viability, and flow cytometric analyses were performed to evaluate apoptosis and cell cycle alterations. Significant decrease in cell viability was observed at high concentrations of piroxicam and deracoxib in both single and combined treatments after 72 h incubation. Combined treatment produced a significantly greater inhibition than that caused by either agent alone. Also apoptotic cell number was increased by both drugs at the cytotoxic concentrations. However, concomitant treatment of cells with piroxicam and deracoxib resulted in significant induction of apoptosis at lower concentrations and accumulation of cells in the G0/G1 phase. Significant cytotoxic effects exhibited by the combination of piroxicam and deracoxib against canine mammary carcinoma cells in vitro suggest an attractive approach for the treatment of canine mammary carcinoma.

  5. Cyclodextrin--piroxicam inclusion complexes: analyses by mass spectrometry and molecular modelling

    Science.gov (United States)

    Gallagher, Richard T.; Ball, Christopher P.; Gatehouse, Deborah R.; Gates, Paul J.; Lobell, Mario; Derrick, Peter J.

    1997-11-01

    Mass spectrometry has been used to investigate the natures of non-covalent complexes formed between the anti-inflammatory drug piroxicam and [alpha]-, [beta]- and [gamma]-cyclodextrins. Energies of these complexes have been calculated by means of molecular modelling. There is a correlation between peak intensities in the mass spectra and the calculated energies.

  6. Effective method for the detection of piroxicam in human plasma using HPLC

    Directory of Open Access Journals (Sweden)

    Adriana Maria CALVO

    2016-01-01

    Full Text Available Abstract Non-steroidal anti-inflammatory drugs (NSAIDs are widely used by the general population to alleviate inflammation and pain after oral surgeries. Piroxicam is among the most commonly used NSAIDs and excels in controlling pain, swelling, trismus and other common symptoms of inflammation. This study aimed to evaluate different concentrations of piroxicam and its major metabolite, 5’-hydroxypiroxicam, in human plasma samples over time using high performance liquid chromatography (HPLC after liquid-liquid extraction. Briefly, 10 volunteers participated in this study after approval by the Ethics Committee of Bauru School of Dentistry, Universidade de São Paulo – USP, Brazil. Volunteers received a single dose oral of piroxicam (20 mg and had blood collected at various times following an established protocol. The methodology of liquid-liquid extraction was effective for determining concentrations of piroxicam in plasma using HPLC in 10 out of 10 volunteers while 5’-hydroxypiroxicam was only detected in 2 out of 10 volunteers.

  7. Stability indicating RP-HPLC method for simultaneous determination of piroxicam and ofloxacin in binary combination.

    Science.gov (United States)

    John, Peter; Azeem, Waqar; Ashfaq, Muhammad; Khan, Islam Ullah; Razzaq, Syed Naeem

    2015-09-01

    A simple and precise RP-HPLC method was developed for simultaneous determination of piroxicam and ofloxacin in pharmaceutical formulations and human serum. Optimum separations of piroxicam, ofloxacin and stress-induced degradation products were achieved by use of Hypersil BDS C8 column (250 x 4.6mm, 5 μm). The mobile phase was a mixture of acetonitrile: 0.012M K2HPO4: 0.008M sodium citrate (both buffers mixed and pH adjusted to 2.8) (50:25:25 v/v/v) delivered at flow rate of 1.5 mL min⁻¹ using DAD at 254 nm. Response was linear function of concentration over the ranges of 70-130 mg mL⁻¹ for piroxicam and ofloxacin (r² ≥ 0.999). The method efficiently separated the analytical peaks from degradation products with acceptable tailing and resolution. The developed method was successfully used for concurrent analysis of piroxicam and ofloxacin in pharmaceutical formulations, human serum and in vitro drug interaction studies.

  8. The effects of piroxicam and deracoxib on canine mammary tumour cell line.

    Science.gov (United States)

    Ustün Alkan, Fulya; Ustüner, Oya; Bakırel, Tülay; Cınar, Suzan; Erten, Gaye; Deniz, Günnur

    2012-01-01

    Cyclooxygenase (COX) inhibitors, already widely used for the treatment of pain and inflammation, are considered as promising compounds for the prevention and treatment of neoplasia. The aim of our study was to determine the direct antiproliferative effects of nonsteroidal anti-inflammatory drugs (NSAIDs), piroxicam and deracoxib, at a variety of concentrations as both single and combined treatments on canine mammary carcinoma cell line CMT-U27 and to understand the mechanisms of cell death. MTT assay was performed to determine cell viability, and flow cytometric analyses were performed to evaluate apoptosis and cell cycle alterations. Significant decrease in cell viability was observed at high concentrations of piroxicam and deracoxib in both single and combined treatments after 72 h incubation. Combined treatment produced a significantly greater inhibition than that caused by either agent alone. Also apoptotic cell number was increased by both drugs at the cytotoxic concentrations. However, concomitant treatment of cells with piroxicam and deracoxib resulted in significant induction of apoptosis at lower concentrations and accumulation of cells in the G₀/G₁ phase. Significant cytotoxic effects exhibited by the combination of piroxicam and deracoxib against canine mammary carcinoma cells in vitro suggest an attractive approach for the treatment of canine mammary carcinoma.

  9. Pharmacodynamics of piroxicam from novel solid lipid microparticles formulated with homolipids from Bos indicus.

    Science.gov (United States)

    Nnamani, Petra O; Attama, Anthony A; Kenechukwu, Franklin C; Ibezim, Emmanuel C; Adikwu, Michael U

    2013-12-01

    The dissolution of piroxicam is a limiting step in its bioavailability on account of its hydrophobicity. The objective of this research was to formulate novel solid lipid microparticles (SLMs) based on homolipids (admixtures of tallow fat (TF) and Softisan(®) 142 (SFT) templated with Phospholipon(®) 90G (P90G), a heterolipid for the delivery of piroxicam. Lipid matrices consisting of TF and SFT in ratios of 1:1, 1:2 and 2:1 were templated with the heterolipid, P90G and characterized by differential scanning calorimetry (DSC). The SLMs produced by hot homogenization technique using the matrices were characterized in terms of thermal properties, particle size, morphology, drug encapsulation efficiency, stability studies and in vitro diffusion studies. In vivo pharmacodynamic study was performed using egg albumin- induced pedal edema in rats. The results showed that addition of Softisan(®) 142 improved the drug holding capacity of the micellar solution of 2:1 mixture of TF and SFT. The in vitro diffusion of piroxicam from this SLM showed maximum release of 87.53 % and followed non-Fickian diffusion kinetic mechanism. At dose equivalence of 10 mg, piroxicamloaded SLMs showed superior in vivo anti-inflammatory properties at 3 h than Feldene(®) and the pure drug sample. This study has shown that surface-modified SLMs could confer favourable properties with respect to drug release and antiinflammatory activity on SLMs for the delivery of piroxicam, thus encouraging further development of the formulations.

  10. THE EFFECT OF PIROXICAM ON THE METABOLISM OF ISOLATED HUMAN CHONDROCYTES

    NARCIS (Netherlands)

    BULSTRA, SK; KUIJER, R; BUURMAN, WA; TERWINDTROUWENHORST, E; GUELEN, PJM; VANDERLINDEN, AJ

    1992-01-01

    The effect of piroxicam on the metabolism of healthy and osteoarthrotic (OA) chondrocytes was studied in vitro. The chondrocytes were obtained from five healthy, five moderately OA, and four severely OA hips or knees. The chondrocytes were cultured in a high-density, short-term in vitro model. In th

  11. Bovine lactoferrin and piroxicam as an adjunct treatment for lymphocytic-plasmacytic gingivitis stomatitis in cats.

    Science.gov (United States)

    Hung, Yi-Ping; Yang, Yi-Ping; Wang, Hsien-Chi; Liao, Jiunn-Wang; Hsu, Wei-Li; Chang, Chao-Chin; Chang, Shih-Chieh

    2014-10-01

    Feline lymphocytic-plasmacytic gingivitis/stomatitis (LPGS) or caudal stomatitis is an inflammatory disease that causes painfully erosive lesions and proliferations of the oral mucosa. The disease is difficult to cure and can affect cats at an early age, resulting in lifetime therapy. In this study, a new treatment using a combination of bovine lactoferrin (bLf) oral spray and oral piroxicam was investigated using a randomized double-blinded clinical trial in 13 cats with caudal stomatitis. Oral lesion grading and scoring of clinical signs were conducted during and after the trial to assess treatment outcome. Oral mucosal biopsies were used to evaluate histological changes during and after treatment. Clinical signs were significantly improved in 77% of the cats. In a 4-week study, clinical signs were considerably ameliorated by oral piroxicam during the first 2 weeks. In a 12-week study, the combined bLf oral spray and piroxicam, when compared with piroxicam alone, exhibited an enhanced effect that reduced the severity of the oral lesions (P = 0.059), while also significantly improving clinical signs (P stomatitis in cats.

  12. Evaluation of piroxicam-β-cyclodextrin as a preemptive analgesic in functional endoscopic sinus surgery

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    G.T. Keleş

    2010-08-01

    Full Text Available The preemptive analgesic efficacy and adverse effects of preoperatively administered piroxicam-β-cyclodextrin for post-endoscopic sinus surgery pain was determined in a prospective, double-blind, randomized, clinical study. Seventy-five American Society of Anesthesiologists status I-II patients, aged 18-65 years, were divided into three groups with similar demographic characteristics: group 1 received 20 mg piroxicam-β-cyclodextrin, group 2 received 40 mg piroxicam-β-cyclodextrin and group 3 received placebo orally before induction of general anesthesia. A blinded observer recorded the incidence and severity of pain at admission to the post-anesthesia care unit (PACU, at 15, 30, and 45 min in the PACU, and 1, 2, 4, 6, and 24 h postoperatively. All patients received patient-controlled morphine analgesia during the postoperative period and consumption was recorded for 24 h. During the PACU period, mean visual analogue scale values were significantly lower in groups 1 and 2 compared to group 3 (P < 0.05. During the postoperative period, morphine consumption was 3.03 ± 2.54, 2.7 ± 2.8, and 5.56 ± 3.12 mg for each group, respectively (P < 0.05. As a side effect, bleeding was observed in groups 1 and 3, nausea and vomiting in all groups, and edema only in group 3. However, no significant differences were detected in any of the parameters analyzed, which also included epigastric pain, constipation/diarrhea and headache. Similar hematological test results were obtained for all groups. Preemptive administration of piroxicam-β-cyclodextrin effectively reduced analgesic consumption, and 40 mg of the drug was more effective than 20 mg piroxicam-β-cyclodextrin without side effects during the postoperative period.

  13. Comparison Efficacy of Topical Piroxicam Gel and Lidocaine with Intravenous Pethidine in Reducing Pain during ESWL

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    F Mohammad Alibeigi

    2011-06-01

    Full Text Available Introduction & Objective: ESWL is a non-invasive method of breaking stones, using acoustic shock waves. Shock waves cause temporary deep visceral pain and discomfort in entry therefore, administration of sedatives is necessary. The purpose of this study was to compare the effect of topical lidocaine and piroxicam gel with intravenous pethidine in reducing pain during ESWL. Materials & Methods: This clinical trial study was performed on 159 patients who referred to Ayatollah Kashani Hospital in Shahrkord for ESWL in 2009. Patients were randomly divided into three-groups. For the first group, intravenous pethidine (0.5 mg/kg alone was administered. The second group received topical piroxicam, and the third group received topical lidocaine in the area of flank for half an hour before ESWL. During the operation, those patients who had unbearable pain, received another 0.5 mg/kg of pethidine. Data was collected using MC Gill questionnaires and analyzed using the SPSS software, using parametric, nonparametric methods and Dunn's Multiple Comparisons tests. Results: The mean of pain scores in the first group (pethidine was 6.2 ± 6.9 while these scores were 3.2 ± 2 .7 and 3.9 ± 3.1 for the second (piroxicam gel and third group (lidocaine gel respectively. The differences in the mean score of pain was significant in the pethidine group compared to the other groups (P <0.05. The average pethidin consumption were 24 ± 16 mg for the first group (pethidine, 10 ± 13 mg for the second group (piroxicam gel, and 5 ± 9 mg for the third group (lidocaine gel. The mean difference was significant in pethidine treated group in comparison with other two groups (P < 0.05. Conclusion: The use of topical piroxicam or lidocaine reduces pain in patients after ESWL It also reduces the need for sedative drugs.

  14. Alleviation of glutamate mediated neuronal insult by piroxicam in rodent model of focal cerebral ischemia: a possible mechanism of GABA agonism.

    Science.gov (United States)

    Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana

    2014-12-01

    Neurotransmitter imbalance is an inevitable outcome in cerebral ischemia that leads to neuronal death. In the present study, we evaluated the effects of piroxicam, a nonsteroidal anti-inflammatory drug (NSAID), on extracellular brain glutamate and γ-aminobutyric acid (GABA) release, survival time, and neuronal cell death. Transient focal cerebral ischemia in male Charles Foster rat led to neuronal infarction and compromised intrinsic antioxidant status. Thirty-minute preadministration of piroxicam (10 mg/kg b.w.) showed a significant (P piroxicam administration in stroke rat significantly reduced (P piroxicam attenuates extracellular glutamate release and also reduces neuronal cell death due to reduction in oxidative stress in cerebral ischemia. Our results also indicate a consequent increase of extracellular GABA in brain regions administered with piroxicam, which hints that piroxicam alleviates glutamate excitotoxicity possibly by GABA agonism.

  15. The detection of piroxicam, tenoxicam and their metabolites in equine urine by electrospray ionisation ion trap mass spectrometry.

    Science.gov (United States)

    McKinney, Andrew R; Suann, Craig J; Stenhouse, Allen M

    2004-01-01

    An investigation has been conducted into the metabolism and urinary excretion of orally administered piroxicam and tenoxicam in the horse. The major component detected in urine after the administration of piroxicam was 5'-hydroxypiroxicam, which was detectable up to 24 h post-administration. Unchanged piroxicam was present only as a minor component. In contrast, unchanged tenoxicam was the major component observed after the administration of tenoxicam, being detectable for 72 h post-administration, while 5'-hydroxytenoxicam was a minor component. Phase II beta-glucuronide conjugation in each case was found to be negligible. The ion trap mass spectral characteristics of piroxicam, tenoxicam, 5'-hydroxypiroxicam and 5'-hydroxytenoxicam under electrospray ionisation conditions were examined in some detail.

  16. Prophylactic intraligamentary injection of piroxicam (feldene) for the management of post-endodontic pain in molar teeth with irreversible pulpitis.

    Science.gov (United States)

    Atbaei, Adnan; Mortazavi, Nazanin

    2012-04-01

    The purpose of this prospective research was to evaluate the post-endodontic pain-reducing effect of piroxicam (feldene), a non-selective non-steroidal anti-inflammatory drug. Pain following endodontic treatment is often linked to the inflammatory process as well as additional central mechanisms. The effects of intraligamentary injection of piroxicam have not previously been studied. Sixty-five patients with irreversible pulpitis were randomly divided into two groups. The active group received intraligamentary injections totalling 0.4 mL of piroxicam, while the placebo group received the same amount of lidocaine. One-appointment endodontic therapy was performed by a single endodontist. Visual Analogue Scale was used to record pain before treatment and 4, 8, 12, 24 and 48 h postoperatively. The decrease in the intensity of post-treatment pain between the two groups was very significant. Intraligamentary injection of piroxicam can be considered an effective method for reducing post-endodontic pain.

  17. Comparative study of tramadol and piroxicam as analgesic for postoperative pain in patients operated for inguinal hernia and hydrocele

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Shukla

    2016-04-01

    Conclusions: Piroxicam provides better and effective analgesia in acute post-operative pain along with the advantage of requiring lesser frequency of administration than tramadol. [Int J Basic Clin Pharmacol 2016; 5(2.000: 312-316

  18. Effects of non-selective (piroxicam and selective (meloxicam cyclo-oxygenase inhibitors on the intestinal contractility of rabbits

    Directory of Open Access Journals (Sweden)

    Warida M. El-Rwegi

    2015-10-01

    Conclusions: Data of the present study may indicate that piroxicam and meloxicam could be used effectively and safely in rabbits for their anti-inflammatory actions in small therapeutic doses. However, in large doses, they (particularly, piroxicam may produce depressant effects on gastrointestinal tract motility that should be taken in consideration in the case of introducing these drugs in therapy with larger doses [Int J Basic Clin Pharmacol 2015; 4(5.000: 924-930

  19. Simultaneous determination of piroxicam, meloxicam and tenoxicam in human plasma by liquid chromatography with tandem mass spectrometry.

    Science.gov (United States)

    Ji, Hye Young; Lee, Hye Won; Kim, Young Hoon; Jeong, Dong Won; Lee, Hye Suk

    2005-11-05

    A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of piroxicam, meloxicam and tenoxicam in human plasma was developed. Piroxicam, meloxicam, tenoxicam and isoxicam (internal standard) were extracted from human plasma with ethyl acetate at acidic pH and analyzed on a Sunfire column with the mobile phase of methanol:ammonium formate (15 mM, pH 3.0) (60:40, v/v). The analytes were detected using a mass spectrometer, equipped with electrospray ion source. The instrument was set in the multiple-reaction-monitoring (MRM) mode. The standard curve was linear (r=1.000) over the concentration range of 0.50-200 ng/ml. The coefficient of variation (CV) and relative error (RE) for intra- and inter-assay statistics at three QC levels were 1.0-5.4% and -5.9 to 2.8%, respectively. The recoveries of piroxicam, meloxicam and tenoxicam ranged from 78.3 to 87.1%, with that of isoxicam being 59.7%. The lower limit of quantification for piroxicam, meloxicam and tenoxicam was 0.50 ng/ml using a 100 microl plasma sample. This method was successfully applied to a pharmacokinetic study of piroxicam after application of transdermal piroxicam patches to humans.

  20. Piroxicam and C-phycocyanin mediated apoptosis in 1,2-dimethylhydrazine dihydrochloride induced colon carcinogenesis: exploring the mitochondrial pathway.

    Science.gov (United States)

    Saini, Manpreet Kaur; Sanyal, Sankar Nath; Vaiphei, Kim

    2012-04-01

    Apoptosis is a synchronized procedure of cell death that is regulated by caspases and proapoptotic proteins. During apoptosis, translocation of cytochrome c, an electron carrier, from mitochondria into the cytosol is regulated by Bcl-2 family members. Cytochrome c in association with an apoptotic protease activating factor (Apaf), a proapoptotic protein essential for cell differentiation and procaspase-9 form the apoptosome complex, which consecutively activates effector caspase, caspase-3, and coordinate the implementation of apoptosis. In the current study, an attempt has been made to gain insight into piroxicam, a traditional nonsteroidal antiinflammatory drug and c-phycocyanin, a biliprotein from Spirulina platensis (cyanobacterium) mediated apoptosis in DMH-induced colon cancer. Male Sprague-Dawley rats were segregated into 5 groups: control, DMH, DMH + piroxicam, DMH + c-phycocyanin, and DMH + piroxicam + c-phycocyanin. Results illustrated that piroxicam and c-phycocyanin treatments stimulate cytochrome c release by downregulating the Bcl-2 (an antiapoptotic protein) expression significantly, while promoting the level of Bax (a proapoptotic protein), thereby activating caspases (caspases-9 and -3) and Apaf-1. The outcomes of the present study clearly signify that piroxicam and c-phycocyanin may mediate mitochondrial-dependent apoptosis in DMH-induced colon cancer. Moreover, apoptosis induction was more apparent in the combination regimen of piroxicam and c-phycocyanin than the individual drugs alone.

  1. FT-Raman and FT-IR studies of 1:2.5 piroxicam: β-cyclodextrin inclusion compound

    Science.gov (United States)

    Bertoluzza, A.; Rossi, M.; Taddei, P.; Redenti, E.; Zanol, M.; Ventura, P.

    1999-05-01

    The FT-Raman and FT-IR spectra of amorphous 1:2.5 piroxicam (P): β-cyclodextrin (βCD) inclusion compound (PβCD) are presented and discussed in comparison with the spectra of the three main modifications of piroxicam (α,β and monohydrate). In the 1700-1200 cm -1 FT-Raman spectrum of 1:2.5 PβCD inclusion compound the bands of βCD are weak and covered by those stronger of piroxicam, differently from the FT-IR spectrum where the bands of βCD are stronger, so covering a large part of the spectrum. Typical FT-Raman marker bands are assigned for the characterization of the three modifications of piroxicam. The FT-Raman spectrum of 1:2.5 PβCD inclusion compound predominantly shows the bands at about 1465 and 1400 cm -1 of the monohydrate, indicating that piroxicam assumes the zwitterionic structure stabilized by interaction with βCD via electrostatic and hydrogen bonds. The dipolar character of 1:2.5 PβCD inclusion compound improves the solubility and the dissolution rate of piroxicam and thus its rate of absorption.

  2. Fast dissolving cyclodextrin complex of piroxicam in solid dispersion part I: influence of β-CD and HPβ-CD on the dissolution rate of piroxicam.

    Science.gov (United States)

    Bouchal, F; Skiba, M; Chaffai, N; Hallouard, F; Fatmi, S; Lahiani-Skiba, M

    2015-01-30

    Sublingual drug delivery is an interesting route for drug having significant hepatic first-pass metabolism or requiring rapid pharmacological effect as for patients suffering from swallowing difficulties, nausea or vomiting. Sublingual absorption could however be limited by the kinetic of drug dissolution. This study evaluated influences of cyclodextrins (β-CD or HP-β-CD) and their different inclusion process (spray-drying or freeze-drying) on the drug dissolution kinetic of solid dispersions in poly(ethylene glycol) (PEG, Mw 6000Da) of piroxicam, used as poor hydrosoluble drug model. A secondary objective was to determine influences of drug dispersion process in PEG (evaporation or melting methods) on the drug dissolution kinetic of piroxicam. Piroxicam solid dispersions containing or not cyclodextrins were characterized by different scanning calorimetry (DSC), Thermogravometry analyser (TGA) and Fourier transform-infrared spectroscopy (FT-IR) spectroscopy. In vitro drug dissolution study of these solid dispersions was then performed. The results demonstrated the high potential and interest of solid dispersions of drug previously included in cyclodextrins for sublingual delivery of hydrophobic drugs. This study also showed the advantages of evaporation method on the melting ones during drug dispersion in PEG. Indeed, drug complexation with cyclodextrins as dispersion by melting prevented the presence in solid dispersions of drug in crystalline form which can represent up to 63%. Moreover, dispersion in PEG by evaporation method gave more porous drug delivery system than with melting methods. This allowed complete (limited at most at 80-90% with melting methods) and quick drug dissolution without rebound effect like with melting ones.

  3. Análise exploratória aplicada no estudo de medicamentos contendo piroxicam Exploratory analysis applied in study of pharmaceutical formulations with piroxicam

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    Graciele Parisotto

    2005-12-01

    Full Text Available A identificação de diferentes formulações de medicamentos manipulados contendo piroxicam foi estudada, empregando espectros de reflexão difusa no infravermelho médio com transformada de Fourier (DRIFTS, em associação com a técnica de análise por agrupamentos hierárquicos (AAH. Os espectros de amostras, de 5 diferentes farmácias de manipulação, contendo piroxicam (10 mg e 20 mg e seus respectivos excipientes, foram adquiridos em um espectrofotômetro NICOLET Magna 550, obtendo-se duas réplicas de cada amostra. Para a análise multivariada, as informações espectrais foram tratadas no programa Pirouette® 2.7 da Infometrix, utilizando-se as regiões espectrais 1340 a 1470 cm-1, 1535 a 1680 cm-1, 2800 a 3004 cm-1 e 3290 a 3400 cm-1. Os dendogramas foram construídos com os dados auto-escalados, e correção do espalhamento da luz (MSC, utilizando três tipos de construção: simples, flexível e incremental. Com a aplicação da análise hierárquica de agrupamentos constatou-se a formação de dois grupos distintos, um contendo os princípios ativos, e outro contendo os excipientes. Os resultados demonstram que a técnica DRIFTS em conjunto com análise por agrupamentos hierárquicos constitui uma alternativa para o controle de qualidade dos processos de produção de medicamentos.The identification of different pharmaceutical formulations with piroxicam was studied, using spectra of diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS, in association with hierarchical cluster analysis (HCA technique. The spectra of samples of the 5 different compounding pharmacies, containing 10 or 20 mg of piroxicam and its respective inactive ingredients, had been collected in Nicolet Magna 550 spectrophotometer. For the multivariate analysis, the spectral information had been processed in software package Pirouette® 2.7 of the Infometrix. The dendograms had been constructed with the autoscaled data, and multiplicative scatter

  4. Spectrophotometric determination of piroxicam and tenoxicam in pharmaceutical formulations using alizarin.

    Science.gov (United States)

    Amin, Alaa S

    2002-07-20

    New spectrophotometric procedures have been established for the quantitation of piroxicam and tenoxicam. The procedures are based on the reaction between the examined drug and alizarin (I), alizarin red S (II), alizarin yellow G (III) or quinalizarin (IV) producing ion-pair complexes which can be measured at the optimum wavelength. The optimization of the reaction conditions is investigated. Beer's law is obeyed in the concentration ranges 0.05-2.40 microg ml(-1), whereas optimum concentration as adopted from Ringbom plots was 0.12-2.25 microg ml(-1). The molar absorptivity, Sandell sensitivity, detection and quantification limits are also calculated. The correlation coefficient was >/=0.9990 (n=10) with a relative standard deviation (R.S.D.) of piroxicam and tenoxicam in their pharmaceutical formulations.

  5. The Effect of Piroxicam Administration before Surgical Removal of Mandibular Mesioangular Third Molar Compared with Acetaminophen.

    Directory of Open Access Journals (Sweden)

    Refoua Y

    2000-05-01

    Full Text Available : 32 patients were entered in randomized double blind clinical research. The patients were"ndivided into two groups. Group A(18 patients were given a single dose of 20 mg Piroxicam one hour"npre-surgery. Group B(14 patients were received 325 mg Acetaminophen every six hours immediately"nafter surgery. The mouth opening was measured pre-surgical treatment. Pain relief was evaluated in both"ngroups lsl and 8th hour after surgery. The mouth opening was measured lsl and 7,b day after surgery. The"nresults showed that the analgesic effects of Piroxicam were higher than acetaminophen, however, the"ncomparison of trismus means revealed no significant difference.

  6. Square Wave Voltammetry: An Alternative Technique to Determinate Piroxicam Release Profiles from Nanostructured Lipid Carriers.

    Science.gov (United States)

    Otarola, Jessica; Garrido, Mariano; Correa, N Mariano; Molina, Patricia G

    2016-08-04

    A new, simple, and fast electrochemical (EC) method has been developed to determine the release profile of piroxicam, a nonsteroidal anti-inflammatory drug, loaded in a drug delivery system based on nanostructured lipid carriers (NLCs). For the first time, the samples were analyzed by using square wave voltammetry, a sensitive EC technique. The piroxicam EC responses allow us to propose a model that explains the experimental results and to subsequently determine the amount of drug loaded into the NLCs formulation as a function of time. In vitro drug release studies showed prolonged drug release (up to 5 days), releasing 60 % of the incorporated drug. The proposed method is a promising and stable alternative for the study of different drug delivery systems.

  7. Effect of the surfactant on the availability of piroxicam as a poorly hydrosoluble drug from suppositories.

    Science.gov (United States)

    Dal Zorro, M; Franceschinis, E; Punchina, A; Realdon, N

    2012-01-01

    The use of surfactants in suppository formulations has been suggested to improve availability of poorly soluble drugs. In the present study, different kinds of surfactants have been investigated to clarify the influence on piroxicam release from suppositories formulated with both lipophilic and hydrophilic bases. Two hydrophilic glucose-derivate surfactants, and a polyoxylglyceride amphiphilic surfactant, all with high HLB values, were investigated for their use in improving drug availability. The two glucose derivate surfactants reduced drug availability from both lipophilic suppositories and hydrophilic formulations, according to longer disintegration times and drug micellization. The more complex surfactant, a lauroyl macrogolglyceride, showed an increase in piroxicam availability from lipophilic suppositories at the higher tested concentrations (15% and 20%). Otherwise, when used in hydrophilic formulations, it was less effective in promoting drug release and even reduced drug availability.

  8. Effects of celecoxib on acid-challenged gastric mucosa of rats: comparison with metamizol and piroxicam.

    Science.gov (United States)

    Berenguer, Bettina; Alarcón De La Lastra, Catalina; Motilva, Virginia; La Casa, Carmen; Herrerias, Juan Manuel; Pozo, David; Calero, María José Martin

    2004-06-01

    Selective COX-2 inhibitors have been shown to produce fewer gastrointestinal adverse reactions than classical NSAIDs. Nevertheless, these new agents may worsen and delay the healing of experimentally induced gastric ulcers in animals. In this study, we compared the effects of a selective COX-2 inhibitor (celecoxib), a preferential COX-1 inhibitor (piroxicam), and a nonnarcotic analgesic (metamizol) on normal gastric mucosa of rats and, on the other hand, in a setting of preexisting acute gastric lesions induced by 0.6 N hydrochloric acid. Under normal conditions, only piroxicam produced appreciable gastric lesions. However, after acid challenge the three assayed drugs induced significant macroscopic and microscopic damage. Myeloperoxidase activity as an index of neutrophil infiltration was elevated with celecoxib and piroxicam on normal gastric mucosa. On inflamed mucosa, celecoxib augmented enzymatic activity at the lower dose, which was parallelled by an increase in the interleukin 1beta level. Acid instillaton produced a significant rise in PGE2 content at 7 hr. Drug treatment after acid challenge decreased prostaglandin values in all cases, although to a lesser extent than after single drug dose administration. COX-2 mRNA expression was visible 1 hr after acid application, whereas COX-2 protein could only be detected at 7 hr. Piroxicam increased both expression levels. All NSAIDs enhanced transforming growth factor alpha and epidermal growth factor receptor immunoreactivity around the acid-induced lesions. It is concluded that selective COX-2 inhibitors, like conventional NSAIDs, impair the healing of gastric damage, and therefore special attention should be paid in patients with gastric pathologies.

  9. Effect of enhancers on the in vitro percutaneous absorption of piroxicam from compounding formulations Efeito de promotores na absorção percutânea in vitro do piroxicam a partir de formulações magistrais

    Directory of Open Access Journals (Sweden)

    Francieli Furlan Bortolon

    2008-09-01

    Full Text Available Formulations of piroxicam in Lanette® (L or Net Fs® (N vehicles, with or without permeation enhancers, the ethanol (E or propylene glycol (P were developed. The piroxicam permeation through porcine ear skin, in a Franz Cell was evaluated, comparing with a commercial product. The permeate was analyzed by high performance liquid chromatography (HPLC using a 5 mm C18 column with mobile phase methanol:phosphate buffer (60:40, at 354 nm and the run time of 10 min. This method was validated and the limit of quantification was 0.138 mg/mL, with linearity over 0.02-5 µg/mL, without endogenous skin interference. The order of piroxicam permeation after 24 h was: LE > L> Feldene® > N > LP > NP > NE. The L based formulations showed greater piroxicam permeation compared with N based formulations, particularly up to 10 h of experiment. The ethanol enhancer provided the highest piroxicam permeation. The commercial product shows a different behavior, providing piroxicam permeation almost after 10 h. These results show the development of effective, simple and economic percutaneous formulations of piroxicam allowing the choice of formulations for higher or lower piroxicam permeation.Formulações de piroxicam com base Lanette® (L ou Net Fs ® (N, com ou sem promotores de absorção (etanol-E ou propilenoglicol-P, foram desenvolvidas. O estudo de permeação de piroxicam das formulações foi realizado em célula de Franz, usando pele de porco e o desempenho foi comparado com a especialidade farmacêutica. O fármaco permeado foi analisado por método desenvolvido por CLAE usando uma coluna analítica C18 de 15 x 0,46 cm, com fase móvel metanol: tampão fosfato (60:40, comprimento de onda de 354 nm e o tempo de corrida foi de 10 min. O ensaio foi validado e apresentou limite de quantificação de 0,138 mg/mL , linearidade na faixa de 0,02-5 µg/mL e não ocorreu interferência de substâncias endógenas da pele ou da formulação. A ordem de permeação de

  10. Photoacoustic evaluation of the penetration of piroxicam gel applied with phonophoresis into human skin

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, F L F D; Barja, P R [Research and Development Institute, UNIVAP, Av. Shishima Hifumi 2911, Sao Jose dos Campos, SP, 12209-010 (Brazil); Acosta-Avalos, D, E-mail: barja@univap.b [Centro Brasileiro de Pesquisas Fisicas (CBPF), R.Xavier Sigaud 150, Rio de Janeiro, RJ, 22290-180 (Brazil)

    2010-03-01

    The photoacoustic (PA) technique has been increasingly employed in biomedical studies, allowing in vivo skin measurements not easily performed with other techniques. It is possible to use PA measurements to evaluate transdermal delivery of products topically applied through manual massage or phonophoresis, that is the utilization of ultrasound waves to enhance drug absorption. The aim of this study was to analyze the influence of the period of phonophoresis application in the transdermal penetration of piroxicam gel. In vivo PA measurements employed a tungsten lamp as light source and a thin aluminum foil closing the PA chamber. The PA signals of the arm (i) clean; and (ii) after phonophoresis were utilized to estimate the concentration of piroxicam into skin. For all (4) volunteers, drug concentration in skin after phonophoresis application was the same for the different application times employed; in this way, phonophoresis for one minute seemed to be sufficient to enhance piroxicam penetration into skin. The actual amount of drug delivered into tissue depends on the person, suggesting a dependency with the skin type, which affects the PA signal level [2]. We conclude that drug delivery depends not only on the application method, but also on the specific skin type.

  11. Optimization and formulation design of carbopol loaded Piroxicam gel using novel penetration enhancers.

    Science.gov (United States)

    Chaudhary, Hema; Rohilla, Ajay; Rathee, Permender; Kumar, Vikash

    2013-04-01

    The aim of the study was to develop and optimize Piroxicam transdermal gel formulation using three-factor, three-level Box-Behnken design by deriving a second-order polynomial equation to construct contour plots for prediction of responses as three selected independent variables with ratio of carbopol 974 (X1), ratio of propylene glycol (PG) (X2) and ratio of ethanol (X3). The dependent variables studied were the skin permeation rate of piroxicam (Y1), viscosity of the gel (Y2) and pH of the gel (Y3). Response surface plots were drawn, statistical validity of the polynomials was established to find the compositions of optimized formulation which was evaluated using the vertical Franz-type diffusion cell. The permeation rate of piroxicam increased proportionally with ethanol concentration but decreased with polymer concentration. The design demonstrated the role of the derived polynomial equation and contour plots in predicting the values of dependent variables for the preparation and optimization of gel formulation.

  12. Mast cells are critical for protection against peptic ulcers induced by the NSAID piroxicam.

    Directory of Open Access Journals (Sweden)

    Daniel D Hampton

    Full Text Available Many commonly used non-steroidal anti-inflammatory drugs (NSAIDs also cause gastrointestinal toxicity, including the development of life-threatening peptic ulcers. We report that mast cell-deficient mice have an extremely high incidence of severe peptic ulceration when exposed to the NSAID piroxicam. This enhanced ulcer susceptibility can be reversed by reconstitution with mast cells. Furthermore, wild type mice treated with diphenhydramine hydrochloride, a commonly used antihistamine that blocks histamine H1 receptors, develop a similarly high incidence of peptic ulcers following piroxicam exposure. The protective effect of mast cells is independent of TNF, blockade of H2 receptors, or acid secretion. These data indicate a critical role for mast cells and the histamine that they produce in prevention and/or repair of piroxicam-induced gastric mucosal injury. Additional studies will be required to determine whether this represents a NSAID class effect that can be exploited to develop novel therapeutic strategies to limit the incidence of NSAID-induced side effects in humans.

  13. Validated Method for the Determination of Piroxicam by Capillary Zone Electrophoresis and Its Application to Tablets

    Directory of Open Access Journals (Sweden)

    Arın Gül Dal

    2014-01-01

    piroxicam in tablets. The separation of piroxicam was conducted in a fused-silica capillary by using 10 mM borate buffer (pH 9.0 containing 10% (v/v methanol as background electrolyte. The optimum conditions determined were 25 kV for separation voltage and 1 s for injection time. Analysis was carried out with UV detection at 204 nm. Naproxen sodium was used as an internal standard. The method was linear over the range of 0.23–28.79 µg/mL. The accuracy and precision were found to be satisfied within the acceptable limits (<2%. The LOD and LOQ were found to be 0.07 and 0.19 µg/mL, respectively. The method described here was applied to tablet dosage forms and the content of a tablet was found in the limits of USP-24 suggestions. To compare the results of capillary electrophoretic method, UV spectrophotometric method was developed and the difference between two methods was found to be insignificant. The capillary zone electrophoretic method developed in this study is rapid, simple, and suitable for routine analysis of piroxicam in pharmaceutical tablets.

  14. The effect of piroxicam on the formation of postoperative, intraabdominal adhesion in rats

    Directory of Open Access Journals (Sweden)

    Maghsoudi Hemmat

    2008-01-01

    Full Text Available Background/Aims: Peritoneal adhesions are fibrous bands of tissues formed between organs that are normally separated and/or between organs and the internal body wall after peritoneal injury. Antiinflammatory agents were used to reduce the initial inflammatory response to tissue injury and, hence, the subsequent formation of adhesion. The aim of this study was to investigate the effect of intraperitoneal instillation of piroxicam on intraperitoneal adhesions. Methods: Eighty Wistar rats were subjected to standardized lesion by using the scraping model and were randomly divided into four groups. Group I (control received no treatment; groups II, III, and IV received 10-12.5 mL of 0.05, 0.1, and 0.2 mg/mL piroxicam solution, respectively, after surgery. On the 14th postoperative day, the adhesion intensity score, inflammatory cell reaction, and the number of adhesion bands were determined. Results: There were no rats with grade 0 adhesions in the control group. There were 10 rats (50% with grade 2 and eight rats (40% with grade 3 adhesions. The adhesion intensity ( P < 0.0001 and the number of adhesion bands ( P < 0.001 were significantly lower in groups III and IV. No significant difference was observed in the adhesion intensity or the number of adhesion bands between groups I and II. Conclusions: Intraperitoneal instillation of piroxicam solution might be useful for preventing peritoneal adhesions.

  15. High-Performance Liquid Chromatography Determination of Meloxicam and Piroxicam with Ultraviolet Detection

    Directory of Open Access Journals (Sweden)

    Sherry Cox

    2014-01-01

    Full Text Available A simple accurate and sensitive high-performance liquid chromatographic method for the determination of meloxicam and piroxicam concentrations in small volume plasma samples has been developed. Following a liquid extraction using chloroform, samples were separated by reversed-phase high-performance liquid chromatography on an XBridge C18 column (4.6 × 250 mm and quantified using ultraviolet detection at 360 nm. The mobile phase was a mixture of water with glacial acetic acid (pH 3.0 and acetonitrile (50 : 50, with a flow rate of 1.0 mL/min. The standard curve ranged from 5 to 10,000 ng/mL for meloxicam in bearded dragon (Pogona vitticeps plasma and piroxicam in crane (Grus rubicunda plasma. Intra- and interassay variability for meloxicam and piroxicam were less than 10% and the average recovery was greater than 90% for both drugs. This method was developed in bearded dragon and crane plasma and should be applicable to any species, making it useful for those investigators dealing with small sample volumes, particularly when conducting pharmacokinetics studies which require multiple sampling from the same animal.

  16. Comparison between paracetamol, piroxicam, their combination, and placebo in postoperative pain management of upper limb orthopedic surgery (a randomized double blind clinical trial

    Directory of Open Access Journals (Sweden)

    Gholamreza Khalili

    2016-01-01

    Conclusion: IV infusion of 15 mg/kg Paracetamol used as a preventive may provide effective analgesia in comparison with IM 0.4 mg/kg Piroxicam or placebo. Addition of Piroxicam to Paracetamol has not much more benefit than Paracetamol alone, in reducing pain after upper limb orthopedic surgery.

  17. Protective effect of antioxidant rich aqueous curry leaf (Murraya koenigii extract against gastro-toxic effects of piroxicam in male Wistar rats

    Directory of Open Access Journals (Sweden)

    Syed Benazir Firdaus

    2014-01-01

    Full Text Available Piroxicam (chemically 4-hydroxy-2-methyl-N-2-pyridinyl-2H-1,2-benzothiazine-3-carboxamide, a classical non-steroidal anti-inflammatory drug (NSAID is orally administered to arthritic patients. Inhibition of prostaglandin E2 (PGE2 synthesis and subsequent free hydroxyl radical generation in vivo exert gastro-toxic side effects on piroxicam treatment. Leaves of curry plant are rich in antioxidants with prolific free radical scavenging activities. This led us to investigate the efficiency of the use of curry leaves in ameliorating piroxicam induced gastric damage. Piroxicam was orally (30 mg per kg body weight administered in male albino Wistar rats to generate gastric ulcers. These rats were orally fed with graded doses of aqueous extract of curry or Murraya koenigii leaves (Cu LE prior to piroxicam administration. Oxidative stress biomarkers, activities of antioxidant and pro-oxidant enzymes, mucin content and nature, PGE2 level, activities of mitochondrial enzymes and histomorphology of gastric tissues were studied. Piroxicam treatment altered all the above mentioned parameters whereas, curry leaf extract pre-treated animals were protected against piroxicam induced alterations. Hence, the protective action of the antioxidant rich Cu LE was investigated to propose a new combination therapy or dietary management to arthritic patients using piroxicam.

  18. Rheological characterization and in vivo evaluation of thermosensitive poloxamer-based hydrogel for intramuscular injection of piroxicam.

    Science.gov (United States)

    Xuan, Jing-Ji; Balakrishnan, Prabagar; Oh, Dong Hoon; Yeo, Woo Hyun; Park, San Man; Yong, Chul Soon; Choi, Han-Gon

    2010-08-16

    To develop an industrially practical thermosensitive injectable hydrogel that is easy to administer, gels quickly in the body and allows sustained release of the drug, poloxamer-based hydrogels containing piroxicam as a model drug were prepared with poloxamer, sodium hydroxide and sodium chloride using the cold method. Their rheological characterization, dissolution and pharmacokinetics after intramuscular administration to rabbits were evaluated. Among the ingredients tested, sodium hydroxide and piroxicam decreased the viscosity and retarded the gelation time of the injectable gel. However, sodium chloride did the opposite. The thermosensitive injectable gel composed of 2.5% piroxicam, 15% P 407, 17% P 188, 0.01% sodium hydroxide and 1.6% sodium chloride was instantly applied to practical industrial product, since it was easy to administer intramuscularly and gelled quickly in the body. The drug was dissolved out of the hydrogels by Fickian diffusion through the extramicellar aqueous channels of the gel matrix. Sodium chloride barely affected the dissolution mechanism or dissolution rate of the drug from the injectable gels. Furthermore, it maintained the plasma concentrations of drug for 4 days and gave a 150-fold higher AUC compared to piroxicam solution. Thus, it would be practically useful for delivering piroxicam in a pattern that allows sustained release for a long time, leading to better bioavailability.

  19. Combination therapy of ifenprodil with piroxicam may be an effective therapeutic intervention in cerebral stroke: a hypothesis.

    Science.gov (United States)

    Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana

    2012-10-01

    Owing to the intricate and multifaceted pathology of cerebral stroke, multiple drug therapy had long been suggested for effective stroke treatment. Therefore, the development of a potential new combination of drug is necessitated which can bring about desirable improved neuroprotection targeting different pathways against ischemic stroke. In this context, we hypothesize the combination effect of Piroxicam, a Non steroidal anti inflammatory drug with Ifenprodil, a NR2b selective NMDAR antagonist in animal model of cerebral ischemia. A few past studies have enumerated the neuroprotective roles of Piroxicam and Ifenprodil administered in singlet against cerebral ischemia in animal model, hence we hypothesized that by using Piroxicam and Ifenprodil in combination would provide additive neuroprotection than either of the agents used alone. In this article, we discuss our hypothesis regarding the possibility of Piroxicam and Ifenprodil as a potent combination which may have a positive therapeutic role in treatment of cerebral ischemia through its anti-inflammatory, anti-apoptotic and anti-oxidative characteristics of Piroxicam with Ifenprodil which has been proved to have neuroprotective, anticonvulsant and antinociceptive effects and has potentials for the treatment of several neuropsychiatric disorders, such as Parkinson's disease alcoholism and drug addiction.

  20. Comparison of Efficacy and Safety of Intramuscular Piroxicam and Tramadol for Post-operative Pain in Patients Undergoing Caesarean Delivery

    Science.gov (United States)

    Thippeswamy, Tejashree; Bengalorkar, Girish M; Mariyappa, Narayanaswamy

    2016-01-01

    Introduction Post-caesarean section pain can be both stressful and unfavourable. Effective and rapid reduction of pain facilitates early ambulation and care of the new born. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and opioids are used for pain relief but they are associated with adverse effects both in the mother and the child. Aim To evaluate efficacy and safety of piroxicam and tramadol in post-caesarean section pain. Materials and Methods Primigravidae who underwent elective caesarean section received either piroxicam 20mg or tramadol 100mg intra-muscularly, following recovery from anaesthesia. Severity of pain was assessed using Visual Analogue Scale (VAS) and side-effects to study drugs were noted. Rescue analgesic butorphanol 2mg was administered if VAS score was more than four. Patient’s satisfaction score was assessed at 12 hours post-operatively. Results Mean age in piroxicam and tramadol groups were 23.32±3.43 and 22.03±2.0 years respectively. Significant reduction in pain was observed at 2, 4, 8, 12 and 24 hours in both groups (ppiroxicam group compared to tramadol. Twenty-one and 12 patients in tramadol and piroxicam groups received rescue analgesic respectively. Sedation and nausea was significantly higher in tramadol group (ppiroxicam group. Conclusion Intra-muscular piroxicam was effective in reducing post-caesarean section pain for 24 hours with minimal side-effects compared to tramadol. PMID:28050391

  1. Determination of piroxicam and its major metabolite 5-hydroxypiroxicam in human plasma by zero-crossing first-derivative spectrophotometry.

    Science.gov (United States)

    Klopas, A; Panderi, I; Parissi-Poulou, M

    1998-07-01

    A zero-crossing first-derivative spectrophotometric method for the determination of piroxicam and its major metabolite 5-hydroxypiroxicam (5-HP) in human plasma is described. This technique permits the quantification of compounds with closely overlapping spectral bands without any separation step. The method consists of direct extraction of the less-ionised forms of piroxicam and 5-hydroxypiroxicam with pure diethyl ether. First derivative values at 343.5 and 332.5 nm for piroxicam and 5-HP, respectively, were obtained. The absolute recovery of the method was found to be 89.4% for piroxicam and 90.3% for 5-HP. Calibration graphs are linear (r better than 0.9998), with zero-intercept, in the concentration range 0.5-12.0 micrograms ml-1 for both compounds. The limits of quantification attained according to the IUPAC definition were 0.29 and 0.27 micrograms ml-1 for piroxicam and 5-HP, respectively. The results obtained by the proposed method were in good agreement with those found by the high-performance liquid chromatographic method (HPLC).

  2. Economic evaluation of the restriction in the use piroxicam in Spain.

    Science.gov (United States)

    Maciá Martínez, Miguel-Ángel

    2015-01-01

    A retrospective economic evaluation was performed on the restriction of the use of piroxicam in Spain, a non-steroidal anti-inflammatory drug, with a proven higher risk of serious gastrointestinal complications compared to other non-steroidal anti-inflammatory drugs with the objective of putting the relevance of these activities into context. A retrospective cost-effectiveness analysis and a budget impact analysis were performed. Costs and cases of serious gastrointestinal complications were compared in the non-intervention (use of piroxicam) and the intervention scenarios (use of other non-steroidal anti-inflammatory drugs). The cost of serious gastrointestinal complications was obtained from the Diagnosis Related Groups and the cost of non-steroidal anti-inflammatory drugs from usage data in the Spanish national health system. The risk of serious gastrointestinal complications was obtained from epidemiological studies. The regulatory intervention was the dominant option. In that sense, 0.81 euros per treated patient were saved, 2.75 cases of serious gastrointestinal complications were avoided per 10,000 patients and 578,608 euros were saved in total in Spain in the first year following the intervention. It is possible to perform complete economical evaluations on pharmacovigilance actions. The intervention performed by the Spanish Agency for Medicines and Medical Devices, AEMPS on piroxicam not only achieved the objective of preventing adverse drug reactions but also resulted in significant economical savings even under conservative assumptions. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  3. A comparison of the experimental and theoretical charge density distributions in two polymorphic modifications of piroxicam

    DEFF Research Database (Denmark)

    Lai, Felcia; Du, Jonathan J.; Williams, Peter A.;

    2016-01-01

    piroxicam molecules, (2a) and (2b), and two water molecules. Geometry differs between (1) and (2) due to the zwitterionic nature of (2) which results in the rotation of the pyridine ring around the C(10)-N(2) bond by approximately 180°. Consequently, the pyridine and amide are no longer co-planar and (2...... is distributed across the benzothiazine carboxamide moiety. The multipole derived lattice energy for (1) is -304 kJ mol(-1) and that for (2) is -571 kJ mol(-1), which is in agreement with the experimentally determined observations of higher solubility and dissolution rates of (1) compared to (2)....

  4. Dynamics of excited-state intramolecular proton transfer reactions in piroxicam. Role of triplet states

    Science.gov (United States)

    Cho, Dae Won; Kim, Yong Hee; Yoon, Minjoong; Jeoung, Sae Chae; Kim, Dongho

    1994-08-01

    The picosecond time-resolved fluorescence and transient absorption behavior of piroxicam at room temperature are reported. The keto tautomer in the excited singlet state ( 1K*) formed via the fast intramolecular proton transfer (≈ 20 ps) is observed. The short-lived (7.5 ns) triplet state of keto tauomer ( 3K*) is generated from 1K * in toluene whereas it is hardly observed in ethanol. Consequently, rapid reverse proton transfer takes place from 3K * to the enol triplet state ( 3E *.

  5. Treatment of superficial thrombophlebitis. A comparative trial between placebo, Hirudoid cream and piroxicam gel.

    Science.gov (United States)

    Bergqvist, D; Brunkwall, J; Jensen, N; Persson, N H

    1990-01-01

    A prospective randomized trial on the treatment of superficial thrombophlebitis has been performed in 68 patients randomized to either Hirudoid cream, piroxicam gel or placebo. Both spontaneous and infusion thrombophlebitis were included. Treatment effect was evaluated using the status of thrombophlebitis, the thrombophlebitic area, pain intensity with a visual analogue scale, and side effects were registered. Both in the treatment groups and the placebo group there was a significant decrease of signs and symptoms during the treatment period. There was no statistical difference between the treatment groups and no difference between spontaneous and infusion thrombophlebitis.

  6. Real-time UV imaging of piroxicam diffusion and distribution from oil solutions into gels mimicking the subcutaneous matrix.

    Science.gov (United States)

    Ye, Fengbin; Larsen, Susan Weng; Yaghmur, Anan; Jensen, Henrik; Larsen, Claus; Østergaard, Jesper

    2012-05-12

    A novel real-time UV imaging approach for non-intrusive investigation of the diffusion and partitioning phenomena occurring during piroxicam release from medium chain triglyceride (MCT) solution into two hydrogel matrices is described. Two binary polymer/buffer gel matrices, 0.5% (w/v) agarose and 25% (w/v) Pluronic F127, were applied as simple models mimicking the subcutaneous tissue. The evolution of the absorbance maps as a function of time provided detailed information on the piroxicam release processes upon the exposure of the gel matrices to MCT. Using calibration curves, the concentration maps of piroxicam in the UV imaging area were determined. Regression of the longitudinal concentration-distance profiles, which were obtained using expressions derived from Fick's second law, provided the diffusivity and the distribution coefficients of piroxicam penetrated into the gels. The obtained MCT-agarose (pH 7.4) distribution coefficient of 1.4 was identical to the MCT-aqueous (pH 7.4) distribution coefficient determined by the shake-flask method whereas that of the MCT-Pluronic F127 system was four times less. The experimental data show that UV imaging may have considerable potential for investigating the transport properties of drug formulations intended for the subcutaneous administration.

  7. Quantum Chemical Calculations and Molecular Docking Studies of Some NSAID Drugs (Aceclofenac, Salicylic Acid, and Piroxicam as 1PGE Inhibitors

    Directory of Open Access Journals (Sweden)

    S. Suresh

    2016-01-01

    Full Text Available The molecular structure of the three compounds Aceclofenac (I, Salicylic Acid (II, and Piroxicam (III has been determined using Gaussian 03W program with B3LYP method using 6-311++G (d,p basis set calculations. The molecular structures were fully optimized with atomic numbering scheme adopted in the study. To understand the mode of binding and molecular interaction, the docking studies of compounds Aceclofenac (I, Salicylic Acid (II, and Piroxicam (III have been carried out with prostaglandin H2 synthase-1 (1PGE as target using induced fit docking. The molecular docking results show that the interactions and energy for Aceclofenac, Salicylic Acid, and Piroxicam show the best results when docked with prostaglandin H2 synthase-1 (1PGE. The hydrogen bonding interactions of compound I (Aceclofenac are prominent with Arginine moiety, those of compound II (Salicylic Acid are prominent with Tyrosine and Serine moieties, and compound III (Piroxicam shows such interaction with Tyrosine and Arginine moieties. These interactions of prostaglandin H2 synthase-1 (1PGE with substrates are responsible for governing COX-1 inhibitor potency which in turn is a direct measure of the potency of the drug.

  8. In vitro release studies of piroxicam from oil-in-water creams and hydroalcoholic gel topical formulations.

    Science.gov (United States)

    Rafiee-Tehrani, M; Mehramizi, A

    2000-04-01

    The importance of piroxicam, a therapeutic anti-inflammatory drug, is well known. Because of gastrointestinal disorders, dermatological dosage forms are recommended most. In our first studies, oil-in-water (O/W) creams of piroxicam (1% concentration) were prepared using glyceryl monostearate (GMS), stearic acid, and triethanolamine as additive ingredients. In our second studies, hydroalcoholic transparent gel formulations of this drug in a 0.5% concentration were prepared using hydroxypropylcellulose (HPC) as the gelling agent. The release of piroxicam from all formulations via dialysis through a cellulose membrane into phosphate buffer pH 6.8 at 37 degrees C was studied. The effects of additives such as propylene glycol and 2-propanol on the drug release were also investigated. The release profiles from the standpoint of diffusion-controlled processes, as well as zero-order and first-order kinetics, were evaluated, and relevant parameters, such as diffusion coefficient, permeability coefficient, and partition coefficient, were calculated. The release obeys both the diffusion mechanism and first-order kinetics. The drug release from gel formulations containing 10%, 20%, and 30% propylene glycol was decreased due to the enhancement of viscosity. However, the limpidity of these formulations was improved. Moreover, the release of drug from gel formulations containing 15% and 20% of 2-propanol was increased. These results show that a hydroalcoholic gel formulation with HPC is a more suitable preparation of piroxicam when compared with an O/W cream formulation.

  9. Effects of various penetration enhancers on percutaneous absorption of piroxicam from emulgels.

    Science.gov (United States)

    Shokri, J; Azarmi, Sh; Fasihi, Z; Hallaj-Nezhadi, S; Nokhodchi, A; Javadzadeh, Y

    2012-10-01

    A suitable emulgel formulation of piroxicam was prepared and its percutaneous permeation was investigated using Wistar rat skin and diffusion cell technique. The concentrations of the drug in receptor phase of diffusion cells were measured using HPLC method. The effect of three types of penetration enhancers (Myrj 52, cineol and Transcutol P) with different concentrations on transdermal permeation of the drug was also evaluated. Flux, Kp and enhancement ratios (ERs) of piroxicam in the presence of enhancers was measured and compared with emulgel base alone and simple commercial gel. The results showed a significant enhancement in the flux from emulgel base compared to hydroalcoholic gel formulation (9.91 folds over simple gel). The highest enhancement ratio (ER=3.11) was observed for Myrj 52 at the concentration of 0.25%. Higher concentrations of Myrj 52did not show any enhancement in the drug flux due to micelle formation and solubilization of the drug by micelles. The increase in solubility, in turn, increases the saturated concentration and reduces the thermodynamic activity of the drug. Transcutol(®) P with concentrations higher than 0.25% w/w showed burst transportation of the drug through the skin. All concentrations of cineol and Transcutol did not show any enhancing effects over emulgel base alone (ER <1).

  10. IMPROVEMENT OF SOLUBILITY AND DISSOLUTION RATE OF PIROXICAM BY SOLID DISPERSIONS IN PEG4000

    Directory of Open Access Journals (Sweden)

    Kulkarni Parthasarathi Keshavarao

    2012-04-01

    Full Text Available The aim of the present study was to enhance the dissolution rate of piroxicam (PX using its solid dispersions (SDs with polyethylene glycol (PEG 6000. The phase solubility behavior of piroxicam in presence of various concentrations of PEG 6000 in distilled water was obtained at 37 °C. The solubility of PX increased with increasing amount of PEG 6000 in water and demonstrating that the reaction conditions became more favorable as the concentration of PEG 6000 increased. The SDs of PX with PEG 6000 were prepared using 1:1, 1:2,1:3,1:4 and1:5 (PX/PEG 6000 ratio by Hot-melt method and solvent evaporation method. Evaluation of the properties of the SDs was performed by using dissolution, Fourier-transform infrared (FTIR spectroscopy, differential scanning calorimetry (DSC. The SDs of PX with PEG 6000 exhibited enhanced dissolution rate of PX and the rate increased with increasing concentration of PEG 6000 in SDs. Mean dissolution time (MDT of PX decreased significantly after preparation of SDs and physical mixture with PEG6000. The FTIR spectroscopic studies revealed that there is no chemical interaction and drug was stable. The DSC studies indicated the microcrystalline or amorphous state of PX in SDs with PEG 6000.

  11. Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery

    Directory of Open Access Journals (Sweden)

    Barroso A.B.

    2006-01-01

    Full Text Available Third molar extraction is a common procedure frequently accompanied by moderate or severe pain, and involves sufficient numbers of patients to make studies relatively easy to perform. The aim of the present study was to determine the efficacy and safety of the therapeutic combination of 10 mg piroxicam, 1 mg dexamethasone, 35 mg orphenadrine citrate, and 2.5 mg cyanocobalamin (Rheumazin® when compared with 20 mg piroxicam alone (Feldene® in mandibular third molar surgery. Eighty patients scheduled for removal of the third molar were included in this randomized and double-blind study. They received (vo Rheumazin or Feldene 30 min after tooth extraction and once daily for 4 consecutive days. Pain was determined by a visual analogue scale and by the need for escape analgesia (paracetamol. Facial swelling was evaluated with a measuring tape and adverse effects and patient satisfaction were recorded. There was no statistically significant difference in facial swelling between Rheumazin and Feldene (control group. Both drugs were equally effective in the control of pain, with Rheumazin displaying less adverse effects than Feldene. Therefore, Rheumazin appears to provide a better risk/benefit ratio in the mandibular molar surgery. Since the side effects resulting from nonsteroidal anti-inflammatory drug administration are a severe limitation to the routine use of these drugs in clinical practice, our results suggest that Rheumazin can be a good choice for third molar removal treatment.

  12. Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery

    Directory of Open Access Journals (Sweden)

    A.B. Barroso

    Full Text Available Third molar extraction is a common procedure frequently accompanied by moderate or severe pain, and involves sufficient numbers of patients to make studies relatively easy to perform. The aim of the present study was to determine the efficacy and safety of the therapeutic combination of 10 mg piroxicam, 1 mg dexamethasone, 35 mg orphenadrine citrate, and 2.5 mg cyanocobalamin (Rheumazin® when compared with 20 mg piroxicam alone (Feldene® in mandibular third molar surgery. Eighty patients scheduled for removal of the third molar were included in this randomized and double-blind study. They received (vo Rheumazin or Feldene 30 min after tooth extraction and once daily for 4 consecutive days. Pain was determined by a visual analogue scale and by the need for escape analgesia (paracetamol. Facial swelling was evaluated with a measuring tape and adverse effects and patient satisfaction were recorded. There was no statistically significant difference in facial swelling between Rheumazin and Feldene (control group. Both drugs were equally effective in the control of pain, with Rheumazin displaying less adverse effects than Feldene. Therefore, Rheumazin appears to provide a better risk/benefit ratio in the mandibular molar surgery. Since the side effects resulting from nonsteroidal anti-inflammatory drug administration are a severe limitation to the routine use of these drugs in clinical practice, our results suggest that Rheumazin can be a good choice for third molar removal treatment.

  13. Effect of virgin olive oil versus piroxicam phonophoresis on exercise-induced anterior knee pain

    Science.gov (United States)

    Nakhostin-Roohi, Babak; Khoshkhahesh, Faegheh; Bohlooli, Shahab

    2016-01-01

    Objective: The main purpose of this study was to evaluate the effects of virgin olive oil phonophoresis on female athletes' anterior knee pain (AKP). Materials and Methods: A double blinded randomized clinical trial was conducted. Ninety-three female athletes suffering from AKP voluntarily participated in this study. Patients were randomly assigned into olive oil (n=31), piroxicam (n=31) or base gel phonophoresis (n=31) groups. At the baseline visit, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was filled by subjects who were then treated with olive oil, piroxicam or pure phonophoresis for 12 sessions. After 6 and 12 sessions of physiotherapy, subjects filled the questionnaire again. Main outcomes were significant improvement in pain, stiffness, physical function, and total WOMAC scores. Results: Although, there was a significant reduction in symptoms of AKP at the end of the therapy in all groups (ppiroxicam and/or phonophoresis group was observed after 6 sessions of therapy (ppiroxicam gel on lowering WOMAC scores of AKP in female athletes and also has several beneficial properties including faster effect and shorter duration of therapy. The exact mechanism of beneficial action of virgin olive oil on AKP is not clear and requires further studies. PMID:27761423

  14. Capillary electrophoresis to determine entrapment efficiency of a nanostructured lipid carrier loaded with piroxicam

    Institute of Scientific and Technical Information of China (English)

    Jessica Otarola; Adriana Guillermina Lista; Beatriz Fernández Band; Mariano Garrido

    2015-01-01

    A simple and fast capillary electrophoresis method has been developed to determine the amount of piroxicam loaded in a drug delivery system based on nanostructured lipid carriers (NLCs). The entrapment efficiency of the nanostructured lipid carrier was estimated by measuring the concentration of drug not entrapped in a suspension of NLC. The influence of different parameters on migration times, peak symmetry, efficiency and resolution was studied; these parameters included the pH of the electrophoretic buffer solution and the applied voltage. The piroxicam peak was obtained with a satisfactory resolution. The separation was carried out using a running buffer composed of 50 mM ammonium acetate and 13.75 mM ammonia at pH 9. The optimal voltage was 20 kV and the cartridge temperature was 20 1C. The corresponding calibration curve was linear over the range of 2.7–5.4 mg/mL of NLC suspension. The reproducibility of migration time and peak area were investigated, and the obtained RSD% values (n ¼ 5) were 0.99 and 2.13, respectively.

  15. Capillary electrophoresis to determine entrapment efficiency of a nanostructured lipid carrier loaded with piroxicam

    Directory of Open Access Journals (Sweden)

    Jessica Otarola

    2015-02-01

    Full Text Available A simple and fast capillary electrophoresis method has been developed to determine the amount of piroxicam loaded in a drug delivery system based on nanostructured lipid carriers (NLCs. The entrapment efficiency of the nanostructured lipid carrier was estimated by measuring the concentration of drug not entrapped in a suspension of NLC. The influence of different parameters on migration times, peak symmetry, efficiency and resolution was studied; these parameters included the pH of the electrophoretic buffer solution and the applied voltage. The piroxicam peak was obtained with a satisfactory resolution. The separation was carried out using a running buffer composed of 50 mM ammonium acetate and 13.75 mM ammonia at pH 9. The optimal voltage was 20 kV and the cartridge temperature was 20 °C. The corresponding calibration curve was linear over the range of 2.7–5.4 µg/mL of NLC suspension. The reproducibility of migration time and peak area were investigated, and the obtained RSD% values (n=5 were 0.99 and 2.13, respectively.

  16. Formulation strategy and evaluation of nanocrystal piroxicam orally disintegrating tablets manufacturing by freeze-drying.

    Science.gov (United States)

    Lai, Francesco; Pini, Elena; Corrias, Francesco; Perricci, Jacopo; Manconi, Maria; Fadda, Anna Maria; Sinico, Chiara

    2014-06-05

    Piroxicam (PRX) is a non-steroidal anti-inflammatory drug characterized by a poor water solubility and consequently by a low oral bioavailability. In this work, different nanocrystal orally disintegrating tablets (ODT) were prepared to enhance piroxicam dissolution rate and saturation solubility. PRX nanocrystals were prepared by means of high pressure homogenization technique using poloxamer 188 as stabilizer. Three different ODTs were prepared with the same nanosuspension using different excipients in order to study their effect on the PRX dissolution properties. PRX nanocrystal size and zeta potential were determined by photon correlation spectroscopy. Additional characterization of PRX nanocrystal ODT was carried out by infrared spectroscopy, X-ray powder diffractometry, differential scanning calorimetry. Dissolution study was performed in distilled water (pH 5.5) and compared with PRX coarse suspension ODT, PRX/poloxamer 188 physical mixture, bulk PRX samples and a PRX commercial ODT. All PRX nanocrystal ODT formulations showed a higher drug dissolution rate than coarse PRX ODT. PRX nanocrystal ODT prepared using gelatin or croscarmellose as excipient showed a higher PRX dissolution rate compared with the commercial formulation and ODT prepared using xanthan gum. Overall results confirmed that improved PRX dissolution rate is due to the increased surface-to-volume ratio due to the nanosized drug particle but also revealed the important role of different excipients used.

  17. Determination of free concentration of piroxicam and naproxen in plasma. The influence of experimental conditions in equilibrium dialysis.

    Science.gov (United States)

    Hundal, O; Rugstad, H E

    1991-01-01

    An equilibrium dialysis method was established in order to investigate possible relationships between free drug concentrations of piroxicam and naproxen and clinical events. Therefore the influence of variations in pH, phosphate concentration and sodium azide concentration of the dialysis buffer on the free concentrations of piroxicam and naproxen was investigated. Piroxicam was found to have a pH-dependent protein binding. Therefore a good control of pH during the dialysis process is necessary. This has been achieved by increasing the buffer capacity of the dialysis buffer, by adding an antibacterial agent to the dialysis buffer and by cleansing the dialysis cells with 70% ethanol before use to prevent bacterial growth. Addition of 0.03% sodium azide as an antibacterial agent and the use of a 0.09 mol/l phosphate buffer gave good pH control. A method to correct for deviations of pH in measurements of free concentrations of piroxicam by a simple mathematical correction has been found. As naproxen was found to have a protein binding independent of pH, a pH-correction is not necessary for this drug. Standardized conditions in determination of protein binding of drugs by equilibrium dialysis are important, as composition of the dialysis buffer and pH of plasma compartment at equilibrium may influence the free concentration measurements. Comparisons of data from experiments using different methods are therefore difficult; the importance of pH-control is stressed. With the methods used in the present investigation, equilibrium dialysis in connection with HPLC, the coefficients of variation for piroxicam and naproxen free concentrations are 5.5% and 7.4%, respectively.

  18. Chemoprevention of DMH-induced rat colon carcinoma initiation by combination administration of piroxicam and C-phycocyanin.

    Science.gov (United States)

    Saini, Manpreet Kaur; Vaiphei, Kim; Sanyal, Sankar Nath

    2012-02-01

    Cancer research illustrated that combinatorial studies can provide significant improvement in safety and effectiveness over the monotherapy regimens. A combination of two drugs may restrain precancerous colon polyps, opening a new possible opportunity for chemoprevention of colon cancer. In this context, chemopreventive efficacy of a combination regimen of C-phycocyanin, a biliprotein present in Spirulina platensis, a cyanobacterium, which is a selective cycloxygenase-2 (COX-2) inhibitor and piroxicam, a traditional non-steroidal anti-inflammatory drug was considered in 1,2 dimethylhyadrazine (DMH)-induced colon carcinogenesis in rats. Western blotting, immunohistochemistry, DNA fragmentation, fluorescent staining, PGE(2) enzyme immunoassay, and carrageenan-induced paw edema test were performed along with morphological and histological analysis. DMH treatment showed a rich presence of preneoplastic lesions such as multiple plaque lesions, aberrant crypt foci, and well-characterized dysplasia. These features were reduced with piroxicam and C-phycocyanin administration. The number of apoptotic cells was featured prominently in all the groups compared with DMH. DMH treatment revealed intact high molecular weight genomic DNA with no signs of laddering/DNA fragmentation while it was noticeable significantly in control and DMH + piroxicam + C-phycocyanin. DMH group showed highest COX-2 expression and PGE(2) level in comparison with other groups. Doses of piroxicam and C-phycocyanin used in the present study were established at an anti-inflammatory range. A combination regimen of piroxicam and C-phycocyanin, rather than individually has the much greater potential for reduction of DMH-induced colon cancer development and COX-2 being the prime possible target in such chemoprevention.

  19. Comparative evaluation of the efficacy of two modes of delivery of Piroxicam (Dolonex®) for the management of postendodontic pain: A randomized control trial

    Science.gov (United States)

    Joshi, Nidhi; Mathew, Sylvia; George, John V.; Hegde, Swaroop; Bhandi, Shilpa; Madhu, K. S.

    2016-01-01

    Background: Alleviating pain is of utmost importance when treating patients with endodontic pain. Aim: To compare and evaluate the efficacy of two modes of delivery of pretreatment Piroxicam (Dolonex®, Pfizer) for the management of postendodontic pain. Materials and Methods: Sixty-six patients with symptomatic irreversible pulpitis were randomly divided into three groups of 22 subjects Group I - control group, no pharmacological intervention, Group II - patients received pretreatment oral Piroxicam (40 mg), Group III - patients received pretreatment intraligamentary injections totaling 0.4 mL of Piroxicam. Single visit endodontic therapy was performed by a single endodontist. Visual analogue scale was used to record pain before treatment and 4, 8, 12, 24, and 48 h postoperatively. Mann–Whitney U-test and Kruskal–Wallis tests were used to analyze the data. Results: The patients in Groups II and III perceived less postendodontic pain as compared to Group I (P Piroxicam was more efficacious. PMID:27563175

  20. Comparison between paracetamol, piroxicam, their combination, and placebo in postoperative pain management of upper limb orthopedic surgery (a randomized double blind clinical trial)

    Science.gov (United States)

    Khalili, Gholamreza; Salimianfard, Marzieh; Zarehzadeh, Abolghasem

    2016-01-01

    Background: Therapeutic superiority of a combination of Paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) over either drug alone remains controversial. We evaluated the efficiency of a combination of Paracetamol and Piroxicam versus each drug alone and also placebo in the management of postoperative pain, in patients who had undergone elective upper limb orthopedic surgery under general anesthesia. Materials and Methods: A total of 100 patients were randomly divided into four groups to receive either intravenous (IV) infusion of Paracetamol, 15 mg/kg., intramuscular (IM) injection of Piroxicam 0.4 mg/kg., their combination or placebo. The pain scores were recorded at the first; second, fourth, sixth, twelfth, and 24 hours after Post Anesthesia Care Unit (PACU) admission. After the operation 0.1 mg/kg of morphine was administered, if the patient needed. Result: The means of the pain scores were 5.26 ± 1.53, 4.09 ± 0.88, 4.36 ± 1.48, and 4.11 ± 1.29, in groups A, B, C, and D, respectively, (Group A: received placebo; Group B: received both Paracetamol and Piroxicam; Group C received Piroxicam; Group D received Paracetamol). Except for differences between the mean pain scores in Groups B and D, the other differences were statistically significant (P value Piroxicam or placebo. Addition of Piroxicam to Paracetamol has not much more benefit than Paracetamol alone, in reducing pain after upper limb orthopedic surgery. PMID:27403409

  1. Piroxicam reverses endotoxin-induced hypotension in rats: contribution of vasoactive eicosanoids and nitric oxide.

    Science.gov (United States)

    Buharalioglu, C Kemal; Korkmaz, Belma; Cuez, Tuba; Sahan-Firat, Seyhan; Sari, Ayse Nihal; Malik, Kafait U; Tunctan, Bahar

    2011-09-01

    Nitric oxide (NO) produced by inducible NO synthase (iNOS) is responsible for endotoxin-induced vascular hyporeactivity and hypotension resulting in multiple organ failure. Endotoxic shock is also characterized by decreased expression of constitutive cyclooxygenase (COX-1), cytochrome P450 (CYP) 4A and endothelial NOS (eNOS). Our previous studies demonstrated that dual inhibition of iNOS and COX with a selective COX-2 inhibitor, NS-398, or a non-selective COX inhibitor, indomethacin, restores blood pressure presumably because of increased production of 20-hydroxyeicosatetraenoic acid (20-HETE) derived from arachidonic acid (AA) by CYP4A in endotoxaemic rats. The aim of this study was to investigate the effects of piroxicam, a preferential COX-1 inhibitor, on the endotoxin-induced changes in blood pressure, expression of COX-1, inducible COX (COX-2), CYP4A1, eNOS, iNOS and heat shock protein 90 (hsp90), and production of PGI(2), PGE(2), 20-HETE and NO. Injection of endotoxin (10 mg/kg, i.p.) to male Wistar rats caused a fall in blood pressure and an increase in heart rate associated with elevated renal 6-keto-PGF(1α) and PGE(2) levels as well as an increase in COX-2 protein expression. Endotoxin also caused an elevation in systemic and renal nitrite levels associated with increased renal iNOS protein expression. In contrast, systemic and renal 20-HETE levels and renal expression of eNOS, COX-1 and CYP4A1 were decreased in endotoxaemic rats. The effects of endotoxin, except for renal COX-1 and eNOS protein expression, were prevented by piroxicam (10 mg/kg, i.p.), given 1 hr after injection of endotoxin. Endotoxin did not change renal hsp90 protein expression. These data suggest that a decrease in the expression and activity of COX-2 and iNOS associated with an increase in CYP4A1 expression and 20-HETE synthesis contributes to the effect of piroxicam to prevent the hypotension during rat endotoxaemia.

  2. A Survey On The Effects Of Iontophoresis Of Piroxicam Gel On Pain And Knee Muscles Strengthn Patients With Knee Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Asghar RezaSoltani

    2012-04-01

    Full Text Available Background and Aim: Knee osteoarthritis is the most common cause of disability in many societies. Therapeutic measures such as using anti-inflammation drugs and physiotherapy programs have been used to suppress knee pain and improve knee joint function in patients with knee osteoarthritis. The aim of this study was to compare the effects of iontophoresis of piroxicam gel, galvanic current with or without piroxicam gel on pain, functional ability and knee muscle strength in patients with knee osteoarthritis.Materials and Method: This study was a clinical trial conducted in Akhtar hospital. Forty two female patients (mean age 58.52 years old with knee osteoarthritis participated in this study. The protocol was performed in Physiotherapy Clinic of Mazandaran Medical University, Mazandaran, Iran. All patients were randomly assigned to three groups. Iontophoresis of piroxicam gel was applied for group 1 (n=14, proxicam gel for group 2 (n=14 and galvanic current for group 3 (n=14. The procedure was carried out for 20-minutes, three times a week and for two following weeks. Knee pain and functional ability were estimated by knee injury and osteoarthritis outcome score (KOOS questioner and the strength of knee extensor and flexor muscles by an isometric device just before the first treatment and immediately after the last treatment times.Results: A significant decrease in pain and a significant increase in functional ability and the strength of knee extensor muscles were resulted in all studied groups (P < 0.05. According to ANOVA test, the level of the percentage difference which was computed for KOOS and knee muscle strength before and after treatments was significantly higher in group 1 than the other two (P < 0.01.Conclusion: Pain and knee functional ability were significantly improved in patients in all three methods. But iontophoresis of piroxicam gel appeared to be more effective in relieving pain and improving knee functional abilities than the

  3. Study on inclusion interaction of piroxicam with beta-cyclodextrin derivatives.

    Science.gov (United States)

    Xiliang, Guo; Yu, Yang; Guoyan, Zhao; Guomei, Zhang; Jianbin, Chao; Shaomin, Shuang

    2003-12-01

    The inclusion behavior of piroxicam (PX) with beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and carboxymethyl-beta-cyclodextrin (CM-beta-CD) was investigated by using steady-state fluorescence and nuclear magnetic resonance (NMR) technique. The various factors affecting the inclusion process were examined in detail. The remarkable fluorescence emission enhancement upon addition of CDs suggested that cyclodextrins (CDs) were most suitable for inclusion of the uncharged species of PX. The stoichiometry of the PX-CDs inclusion complexes was 1:1, except for beta-CD where a 1:2 inclusion complex was formed. The formation constants showed the strongest inclusion capacity of beta-CD. NMR showed the inclusion mode of PX with CDs.

  4. Study on inclusion interaction of piroxicam with β-cyclodextrin derivatives

    Science.gov (United States)

    Xiliang, Guo; Yu, Yang; Guoyan, Zhao; Guomei, Zhang; Jianbin, Chao; Shaomin, Shuang

    2003-12-01

    The inclusion behavior of piroxicam (PX) with β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), and carboxymethyl-β-cyclodextrin (CM-β-CD) was investigated by using steady-state fluorescence and nuclear magnetic resonance (NMR) technique. The various factors affecting the inclusion process were examined in detail. The remarkable fluorescence emission enhancement upon addition of CDs suggested that cyclodextrins (CDs) were most suitable for inclusion of the uncharged species of PX. The stoichiometry of the PX-CDs inclusion complexes was 1:1, except for β-CD where a 1:2 inclusion complex was formed. The formation constants showed the strongest inclusion capacity of β-CD. NMR showed the inclusion mode of PX with CDs.

  5. Photophysical studies of oxicam group of NSAIDs: piroxicam, meloxicam and tenoxicam

    Science.gov (United States)

    Banerjee, Rona; Chakraborty, Hirak; Sarkar, Munna

    2003-04-01

    Oxicam group of non steroidal anti-inflammatory drugs has been chosen as a prototype molecular group that shows diverse biological functions and dynamic structural features. Photophysical studies of three drugs from this group viz., piroxicam, meloxicam and tenoxicam have been carried out in different solvents with varying polarity, H-bond character and viscosity. The spectral responses of different prototropic forms of these drugs towards varying solvent parameters have been studied, with the aim to characterize their interaction in biomimetic environment non-invasively. The nature of the lowest transition has been identified. The extinction coefficient, quantum yield and viscosity dependence on the nature of the solvents, all indicate the extreme sensitivity of these drugs to their microenvironment.

  6. Primary frontal sinus squamous cell carcinoma in three dogs treated with piroxicam combined with carboplatin or toceranib.

    Science.gov (United States)

    de Vos, J; Ramos Vega, S; Noorman, E; de Vos, P

    2012-09-01

    In human medicine, primary frontal sinus squamous cell carcinoma (pFS-SCC) is not frequently reported. In veterinary medicine, frontal sinus SCC is exclusively described as an extension of nasal cavity SCC. To our knowledge, this is the first publication concerning canine pFS-SCC, diagnosed using histology or cytology and medical imaging, in three dogs. The tumours extended into the orbit or brain cavity, without nasal involvement. Treatment was initiated with piroxicam-carboplatin. Prolongation of carboplatin delivery with a low dose intensity was performed on dogs with a favourable initial response. Dog 1 achieved a complete remission (CR), but was euthanized 344 days after start of therapy. Dog 2, still alive 3 years after start of therapy and in CR, received 14 carboplatin deliveries. In dog 3, after changing the treatment protocol into piroxicam-toceranib, a significant tumour reduction occurred, but the dog was euthanized after 195 days because of a relapse.

  7. The selective and non-selective cyclooxygenase inhibitors valdecoxib and piroxicam induce the same postoperative analgesia and control of trismus and swelling after lower third molar removal

    Directory of Open Access Journals (Sweden)

    V. Benetello

    2007-08-01

    Full Text Available We compared the clinical efficacy of orally administered valdecoxib and piroxicam for the prevention of pain, trismus and swelling after removal of horizontally and totally intrabony impacted lower third molars. Twenty-five patients were scheduled to undergo removal of symmetrically positioned lower third molars in two separate appointments. Valdecoxib (40 mg or piroxicam (20 mg was administered in a double-blind, randomized and crossed manner for 4 days after the surgical procedures. Objective and subjective parameters were recorded for comparison of postoperative courses. Both agents were effective for postoperative pain relief (N = 19. There was a similar mouth opening at suture removal compared with the preoperative values (86.14 ± 4.36 and 93.12 ± 3.70% of the initial measure for valdecoxib and piroxicam, respectively; ANOVA. There was no significant difference regarding the total amount of rescue medication taken by the patients treated with valdecoxib or piroxicam (173.08 ± 91.21 and 461.54 ± 199.85 mg, respectively; Wilcoxon test. There were no significant differences concerning the swelling observed on the second postoperative day compared to baseline measures (6.15 ± 1.84 and 8.46 ± 2.04 mm for valdecoxib and piroxicam, respectively; ANOVA or on the seventh postoperative day (1.69 ± 1.61 and 2.23 ± 2.09 mm for valdecoxib and piroxicam, respectively; ANOVA. The cyclooxygenase-2 selective inhibitor valdecoxib is as effective as the non-selective cyclooxygenase inhibitor piroxicam for pain, trismus and swelling control after removal of horizontally and totally intrabony impacted lower third molars.

  8. Effects on muscle performance of NSAID treatment with Piroxicam versus placebo in geriatric patients with acute infection-induced inflammation. a double blind randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Beyer Ingo

    2011-12-01

    Full Text Available Abstract Background Inflammation is the main cause of disease-associated muscle wasting. In a previous single blind study we have demonstrated improved recovery of muscle endurance following celecoxib treatment in hospitalized geriatric patients with acute infection. Here we further evaluate NSAID treatment with piroxicam in a double blind RCT and investigate the role of cytokines and heat shock proteins (Hsp with respect to muscle performance. We hypothesized that NSAID treatment would preserve muscle performance better than antibiotic treatment alone, by reducing infection-associated inflammation and by increasing expression of cytoprotective Hsp. Methods Consecutive admissions to the geriatric ward were screened. 30 Caucasian patients, median age 84.5 years, with acute infection-induced inflammation and serum levels of CRP > 10 mg/L were included and randomized to active treatment with 10 mg piroxicam daily or placebo. Assessment comprised general clinical and biochemical parameters, 25 cytokines in serum, intra-and extracellular Hsp27 and Hsp70, Elderly Mobility Scale (EMS scores, grip strength (GS, fatigue resistance (FR and lean body mass (LBM. Patients were evaluated until discharge with a maximum of 3 weeks after treatment allocation. Results EMS scores, FR and grip work (GW, a measure taking into account GS and FR, significantly improved with piroxicam, but not with placebo. Early decreases in IL-6 serum levels with piroxicam correlated with better muscle performance at week 2. Basal expression of Hsp27 in monocytes without heat challenge (WHC was positively correlated with FR at baseline and significantly increased by treatment with piroxicam compared to placebo. Profound modifications in the relationships between cytokines or Hsp and changes in muscle parameters were observed in the piroxicam group. Conclusions Piroxicam improves clinically relevant measures of muscle performance and mobility in geriatric patients hospitalized with

  9. Thermodynamic solubility of piroxicam in propylene glycol + water mixtures at 298.2-323.2 K: Data report and modeling

    Directory of Open Access Journals (Sweden)

    Soltanpour Shahla

    2015-01-01

    Full Text Available The solubility of piroxicam (66 data points in binary mixtures of propylene glycol (PG + water at six different temperatures which ranged from 298.2 K to 323.2 K were reported. Three different cosolvency models; Yalkowsky, Jouyban-Acree and combined version of the Jouyban-Acree model with van’t Hoff approach, have been used for correlating the reported data. All the analyses results show the acceptable range of the error percentages.

  10. 吡罗昔康贴剂的研制%Study on the preparation of piroxicam films

    Institute of Scientific and Technical Information of China (English)

    周萍

    2001-01-01

    目的 制备吡罗昔康贴剂,研究其透皮吸收性能。方法 以高分子材料制备吡逻昔康贴剂,大鼠皮为模型皮肤,采用改良Franz扩散池分别进行药物经皮释放试验和渗透嗽验,并测定了人体平均透皮速率。结果 吡罗昔康贴剂体外释放速率为64.31 μg*cm-2*h-1,体外透皮速率为14.86 μg*cm-2*h-1,人体平均透皮速率为11.94 μg*cm-2*h-1。结论 吡罗昔康贴剂为一种新颖的控释型外用制剂。%OBJECTIVE To prepare the piroxicam films and study its characteristics of transdermal delivery.METHODS Different high polymers were employed to prepare piroxicam films.Rat abdomen skin and modified Franz diffusion cells were used in the drug penetration tests and release tests.The percutaneous penetration rate was investigated.RESULTS The release rate of piroxicam films was 64.31 μg*cm-2*h-1.The in vitro permeation rate was 14.86 μg*cm-2*h-1.The percutaneous penetration rate was 11.94 μg*cm-2*h-1.CONCLUSION Piroxicam films was developed.

  11. Piroxicam and intracavitary platinum-based chemotherapy for the treatment of advanced mesothelioma in pets: preliminary observations

    OpenAIRE

    2008-01-01

    Abstract Malignant Mesothelioma is an uncommon and very aggressive tumor that accounts for 1% of all the deaths secondary to malignancy in humans. Interestingly, this neoplasm has been occasionally described in companion animals as well. Aim of this study was the preclinical evaluation of the combination of piroxicam with platinum-based intracavitary chemotherapy in pets. Three companion animals have been treated in a three years period with this combination. Diagnosis was obtained by ultraso...

  12. A comparison between the effects of topical piroxicam and EMLA cream on fistula cannulation pain in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Mehdi Mohseni

    2015-02-01

    Full Text Available Background: Patients with end-stage renal failure, consider recurrent fistula cannulation pain as the most severe stress, resulted from the treatment process, and a major concern of their life. Nurses as one of the main targets of their actions, have a duty to relieve the pain. Accordingly, this study was conducted to determine the effectiveness of two topical piroxicam and EMLA on fistula cannulation pain intensity in hemodialysis patients. Materials and Methods: This clinical trial study was conducted on 75 patients referred to dialysis ward in Khorramabad Shohada hospital in 2013. Patients were randomly divided into three groups: group A (piroxicam, group B (EMLA and group C (placebo. Data collection tools included demographic information, Visual Analogue Scale (VAS and a checklist for possible side effects of the drugs. Pain intensity during fistula cannulation was measured in the three groups on two occasions, before and after the intervention. The collected data were then analyzed using Mann-Whitney and Kruskal-Wallis tests and SPSS19 software. Results: The median pain intensity before and after the intervention in the three groups, was significantly different (p <0/001. The highest median pain intensity reduction was in the EMLA, piroxicam and placebo groups respectively. In addition, a short term side effect (blanching in 16% of the subjects was detected in EMLA group. Conclusion:The results showed that EMLA cream was more effective than piroxicam gel in reducing the pain intensity of fistula cannulation in dialysis patients. Therefore, our study recommends to use EMLA cream as an easy method with ability to work by patients, to reduction pain during fistula cannulation in hemodialysis patients.

  13. Crystal structure of a 2:1 piroxicam–gentisic acid co-crystal featuring neutral and zwitterionic piroxicam molecules

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Horstman

    2016-12-01

    Full Text Available A new 2:1 co-crystal of piroxicam and gentisic acid [systematic name: 4-hydroxy-1,1-dioxo-N-(pyridin-2-yl-2H-1λ6,2-benzothiazine-3-carboxamide–2-(4-oxido-1,1-dioxo-2H-1λ6,2-benzothiazine-3-amidopyridin-1-ium–2,5-dihydroxybenzoic acid, 2C15H13N3O4S·C7H6O4] has been synthesized using a microfluidic platform and initially identified using Raman spectroscopy. In the co-crystal, one piroxicam molecule is in its neutral form and an intramolecular O—H...O hydrogen bond is observed. The other piroxicam molecule is zwitterionic (proton transfer from the OH group to the pyridine N atom and two intramolecular N—H...O hydrogen bonds occur. The gentisic acid molecule shows whole-molecule disorder over two sets of sites in a 0.809 (2:0.191 (2 ratio. In the crystal, extensive hydrogen bonding between the components forms layers propagating in the ab plane.

  14. Piroxicam inhibits Masitinib-induced cyclooxygenase 2 expression in oral squamous cell carcinoma cells in vitro.

    Science.gov (United States)

    Rathore, Kusum; Alexander, Mary; Cekanova, Maria

    2014-08-01

    Development and characterization of animal models for human cancers is important for the improvement of diagnosis and therapy. The oral squamous cell carcinoma (OSCC) of domestic animals resembles human OSCC in many aspects; thus, cell lines derived from OSCC of cats and dogs are a valuable model for human OSCC. We characterized 1 feline OSCC (FeOSCC-Sidney) and 1 canine OSCC (K9OSCC-Abby) cell line and compared their characteristics with human OSCC cell line hSCC-25. We calculated the doubling time of the new OSCC cell lines and evaluated the expression profiles of cancer-related markers and cell-cycle proteins such as c-kit, platelet-derived growth factor receptor, vascular endothelial growth factor receptor, epidermal growth factor receptor, cyclooxygenase (COX)-1, COX-2, and p27 by immunocytochemistry and Western blot analysis. We evaluated the effects of novel receptor tyrosine kinase inhibitor (Masitinib, AB1010) and the nonsteroidal anti-inflammatory drug piroxicam on the previously mentioned OSCC cells. Interestingly, AB1010 increased expression levels of COX-2 in all tested OSCCs. Cotreatment of piroxicam with Masitinib significantly inhibited cell proliferation of OSCC as compared to either drug alone through the c-kit and AKT signaling pathways. Piroxicam inhibited Masitinib-induced COX-2 expression in all tested OSCCs. Therefore, targeting these two signaling pathways simultaneously was more efficient for inhibition of OSCCs across these species.

  15. Predictive validity and immune cell involvement in the pathogenesis of piroxicam-accelerated colitis in interleukin-10 knockout mice

    DEFF Research Database (Denmark)

    Holgersen, Kristine; Kvist, Peter Helding; Hansen, Axel Jacob Kornerup

    2014-01-01

    Piroxicam administration is a method for induction of enterocolitis in interleukin-10 knockout (IL-10 k.o.) mice. The piroxicam-accelerated colitis (PAC) IL-10 k.o. model combines a dysregulated immune response against the gut microbiota with a decreased mucosal integrity. The predictive validity...... and pathogenic mechanisms of the model have not been thoroughly investigated. In this study, IL-10 k.o. mice received piroxicam in the chow, and model qualification was performed by examining the efficacy of prophylactic anti-IL-12/23p40 monoclonal antibody (mAb), anti-TNFαmAb, cyclosporine A (CsA) and oral...... immunohistochemistry were performed on colon tissue. Treatments with anti-IL-12/23p40 mAb and CsA prevented disease in PAC IL-10 k.o. mice and reduced IFNγ, IL-17A, MPO and calprotectin levels in colon. Anti-TNFαmAb treatment caused amelioration of selected clinical parameters. No effect of prednisolonewas detected...

  16. Sublingual ketorolac and sublingual piroxicam are equally effective for postoperative pain, trismus, and swelling management in lower third molar removal.

    Science.gov (United States)

    Trindade, Paulo A K; Giglio, Fernando P M; Colombini-Ishikiriama, Bella L; Calvo, Adriana M; Modena, Karin Cristina S; Ribeiro, Debora A; Dionísio, Thiago J; Brozoski, Daniel T; Lauris, José Roberto P; Faria, Flávio Augusto C; Santos, Carlos F

    2012-07-01

    Lower third molar removal provides a clinical model for studying analgesic drugs. The present study's aim was to compare the clinical efficacy of sublingual ketorolac and sublingual piroxicam in managing pain, trismus and swelling after lower third molar extraction in adult volunteers. In this double-blinded, randomized, crossover investigation, 47 volunteers received for 4 days ketorolac sublingually (10 mg 4 times daily) and piroxicam sublingually (20 mg once daily) during 2 separate appointments after lower third molar extraction of symmetrically positioned lower third molars. A surgeon evaluated objective parameters (surgery duration, mouth opening, rescue analgesic medication, and facial swelling) and volunteers documented subjective parameters (postoperative pain and global evaluation), comparing postoperative results for a total of 7 days after surgery. The means of the objective and subjective parameters were compared for statistical significance (P .05). Additionally, values for mouth openings measured just before surgery and immediately after suture removal 7 days later were similar among volunteers (P > .05), and the type of nonsteroidal antiinflammatory drug (NSAID) used in this study showed no significant differences between swellings on the second or seventh days after surgery (P > .05). Pain, trismus, and swelling after lower third molar extraction, independent of surgical difficulty, were successfully controlled by sublingual ketorolac (10 mg 4 times daily) or sublingual piroxicam (20 mg once daily), and no significant differences were observed between the NSAIDs evaluated. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Structural and thermal characterization of ternary complexes of piroxicam and alanine with transition metals: Uranyl binary and ternary complexes of piroxicam. Spectroscopic characterization and properties of metal complexes

    Science.gov (United States)

    Mohamed, Gehad G.

    2005-12-01

    Ternary Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and UO 2(II) complexes with piroxicam (Pir) drug (H 2L 1) and dl-alanine (Ala) (HL 2) and also the binary UO 2(II) complex with Pir were studied. The structures of the complexes were elucidated using elemental, IR, molar conductance, magnetic moment, diffused reflectance and thermal analyses. The UO 2(II) binary complex was isolated in 1:2 ratio with the formula [UO 2(H 2L) 2](NO 3) 2. The ternary complexes were isolated in 1:1:1 (M:H 2L 1:L 2) ratios. The solid complexes were isolated in the general formulae [M(H 2L)(L 2)(Cl) n(H 2O) m]· yH 2O (M = Fe(III) ( n = 2, m = 0, y = 1), Co(II) ( n = 1, m = 1, y = 2) and Ni(II) ( n = 1, m = 1, y = 0)); [M(H 2L)(L 2)](X) z· yH 2O (M = Cu(II) (X = AcO, z = 1, y = 0), Zn(II) (X = AcO, z = 1, y = 3) and UO 2(II) (X = NO 3, z = 1, y = 2)). Pir behaves as a neutral bidentate ligand coordinated to the metal ions via the pyridine-N and carbonyl-O groups, while Ala behaves as a uninegatively bidentate ligand coordinated to the metal ions via the deprotonated carboxylate-O and amino-N. The magnetic and reflectance spectral data show that the complexes have octahedral geometry except Cu(II) and Zn(II) complexes have tetrahedral structures. The thermal decomposition of the complexes was discussed in relation to structure, and the thermodynamic parameters of the decomposition stages were evaluated.

  18. The dissolution enhancement of piroxicam in its physical mixtures and solid dispersion formulations using gluconolactone and glucosamine hydrochloride as potential carriers.

    Science.gov (United States)

    Al-Hamidi, Hiba; Obeidat, Wasfy M; Nokhodchi, Ali

    2015-01-01

    The solid dispersion technique is one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs; however this is reliant on a suitable carrier and solvent being selected. The work presented explores amino sugars (d-glucosamine HCl and d-gluconolactone) as potential hydrophilic carriers to improve dissolution rate of a poorly water-soluble drug, piroxicam, from physical mixtures and solid dispersion formulations. Solid dispersions of the drug and carrier were prepared using different ratios by the conventional solvent evaporation method. Acetone was used as solvent in the preparation of solid dispersions. Physical mixtures of piroxicam and carrier were also prepared for comparison. The properties of all solid dispersions and physical mixtures were studied using a dissolution tester, Fourier transform infrared, XRD, SEM and differential scanning calorimetry. These results showed that the presence of glucosamine or gluconolactone can increase dissolution rate of piroxicam compared to pure piroxicam. Glucosamine or Gluconolactone could be used as carrier in solid dispersion formulations and physical mixtures to enhance the dissolution rate. Solid state studies showed that no significant changes occurred for piroxicam in physical mixtures and solid dispersion.

  19. The nonsteroidal antiinflammatory drug piroxicam reverses the onset of depressive-like behavior in 6-OHDA animal model of Parkinson's disease.

    Science.gov (United States)

    Santiago, R M; Tonin, F S; Barbiero, J; Zaminelli, T; Boschen, S L; Andreatini, R; Da Cunha, C; Lima, M M S; Vital, M A B F

    2015-08-06

    Depression is one of the most common psychiatric symptoms in patients with Parkinson's disease (PD). Some authors have reported that depression is characterized by activation of the inflammatory response. Animal models of PD also present with depressive-like behavior, such as increased immobility time in the modified forced swim test and anhedonia-like behavior in the sucrose preference test. Considering the potential neuroprotective effect of nonsteroidal antiinflammatory drugs in neurodegenerative diseases, the objective of the present study was to investigate the effects of piroxicam on depressive-like behavior in male Wistar rats lesioned with 6-hydroxydopamine (6-OHDA) in the substantia nigra (SN). Antidepressant-like effects were observed after prolonged administration of piroxicam for 21days. In the forced swim test, the 6-OHDA+saline group exhibited significant reductions in swimming time and increased immobility time compared with the sham+saline. In the sucrose preference test, the 6-OHDA+piroxicam group exhibited no reduction of sucrose preference compared with the sham+saline, with significant effects of treatment and time and a significant treatment×time interaction. 5-Hydroxytryptamine (5-HT) levels significantly decreased in the hippocampus in the 6-OHDA+saline group and not changed in the 6-OHDA+piroxicam group when compared with the sham+saline on day 21. In conclusion, 21-day treatment with piroxicam reversed the onset of depressive-like behavior and prevented the reduction of hippocampal 5-HT levels.

  20. Increased localized delivery of piroxicam by cationic nanoparticles after intra-articular injection

    Directory of Open Access Journals (Sweden)

    Kim SR

    2016-11-01

    Full Text Available Sung Rae Kim,1 Myoung Jin Ho,2 Sang Hyun Kim,1 Ha Ra Cho,2 Han Sol Kim,2 Yong Seok Choi,2 Young Wook Choi,1 Myung Joo Kang2 1Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul, 2College of Pharmacy, Dankook University, Cheonan, Chungnam, South Korea Abstract: Piroxicam (PRX, a potent nonsteroidal anti-inflammatory drug, is prescribed to relieve postoperative and/or chronic joint pain. However, its oral administration often results in serious gastrointestinal adverse effects including duodenal ulceration. Thus, a novel cationic nanoparticle (NP was explored to minimize the systemic exposure and increase the retention time of PRX in the joint after intra-articular (IA injection, by forming micrometer-sized electrostatic clusters with endogenous hyaluronic acid (HA in the synovial cavity. PRX-loaded NPs consisting of poly(lactic-co-glycolic acid, Eudragit RL, and polyvinyl alcohol were constructed with the following characteristics: particle size of 220 nm, zeta potential of 11.5 mV in phosphate-buffered saline, and loading amount of 4.0% (w/w of PRX. In optical and hyperspectral observations, the cationic NPs formed more than 50 µm-sized aggregates with HA, which was larger than the intercellular gaps between synoviocytes. In an in vivo pharmacokinetic study in rats, area under the plasma concentration–time curve (AUC0–24 h and maximum plasma concentration (Cmax of PRX after IA injection of the cationic NPs were <70% (P<0.05 and 60% (P<0.05, respectively, compared to those obtained from drug solution. Moreover, the drug concentration in joint tissue 24 h after dosing with the cationic NPs was 3.2-fold (P<0.05 and 1.8-fold (P<0.05 higher than that from drug solution and neutrally charged NPs, respectively. Therefore, we recommend the IA cationic NP therapy as an effective alternative to traditional oral therapy with PRX, as it increases drug retention selectively in the joint. Keywords: piroxicam

  1. Quantification of piroxicam and 5'-hydroxypiroxicam in human plasma and saliva using liquid chromatography-tandem mass spectrometry following oral administration.

    Science.gov (United States)

    Calvo, Adriana Maria; Santos, Gabriel Mulinari; Dionísio, Thiago José; Marques, Maria Paula; Brozoski, Daniel Thomas; Lanchote, Vera Lúcia; Fernandes, Maria Helena Raposo; Faria, Flávio Augusto Cardoso; Santos, Carlos Ferreira

    2016-02-20

    Saliva sampling used to quantify piroxicam and 5'-hydroxypiroxicam is a noninvasive and painless method when compared to sequential blood sampling. For that, a rapid, selective and sensitive liquid chromatography-tandem mass spectrometric method for simultaneous determination of piroxicam and 5'-hydroxypiroxicam in saliva and human plasma was developed and validated. Piroxicam and its major metabolite were separated using a LiChroCART 125-4 RP Select-B Sorbent C18 column using a mixture of methanol and 2% phosphoric acid (pH 2.7) (70:30, v/v) for the mobile phase with a flow injection of 1mL/min. The run time was 4min. Volunteers had saliva and blood sampled before, 1, 2, 3, 4, 5, 6, 8, 11, 24, 48 and 72h after taking a 20mg oral dose of piroxicam. The pharmacokinetic parameters of piroxicam in plasma samples were as follows: AUC0-72 (64819hng/mL), predicted clearance (0.2L/h), distribution volume (14.8L), elimination half-life (50.7h) and saliva/plasma concentration ratio (0.003). The estimation of all pharmacokinetic parameters for 5'-hydroxypiroxicam would require collections beyond 72h; however, it was possible to quantify the mean maximum concentration (133ng/mL), time to peak concentration (53.6h), mean AUC0-72 (6213hng/mL), predicted clearance (110.3L/h) and saliva/plasma concentration ratio (0.04). The developed methods proved effective and sensitive for determining the lower quantification limit of piroxicam in plasma (6.1ng/mL) and saliva (0.15ng/mL) and of 5'-hydroxypiroxicam in plasma (1.2ng/mL) and saliva (0.15ng/mL).

  2. Rapid quantification of piroxicam in piroxicam preparations by using LC-MS/MS%LC-MS/MS法快速测定吡罗昔康制剂中吡罗昔康含量

    Institute of Scientific and Technical Information of China (English)

    张军民; 傅思武; 赵晋; 郭裕临; 石晓峰

    2012-01-01

    An improved method was developed for the quantification of piroxicam in piroxicam preparation by ultra fast liquid chromatography/tandem mass spectrometry ( LC/MS/MS) . METHOD Sample preparation consisted of extraction by adding 0.1 mol/L hydrochloric acid in methanol, filtration with microporous membrane and centrifugation of the sample subsequently. LC/MS/MS detection was performed by using a triple-stage quadrupole mass spectrometer working in multiple reaction monitoring mode ( MRM) with positive eleclrospray ionization(ESI) , using the transitions of m/z 332. 2→94. 8 of piroxicam. Chromatographic separation was achieved using a 3. 0mm x 75mm, 2. 0 μm Shim-pack XR-ODS column with isocratic flow and elution with acetonitrile-water-formic acid (60;40:0.1, V/V/V) and a flow-rate of 0.4 mL/min. The analyte was quantified in a single run within 3 min. RESULTS Linearity was demonstrated over the expected concentration range of 2.5 ~ 1000. 0 ng/mL. The lower limit of quantification (LLOQ) was 2.5 ng/μmL. Intra-day precision expressed as RSD was less than 3.2%, while inter-day result was less than 3.8% for piroxicam. CONCLUSION The method has good repeatability, high sensitivity and more convenient, and can be successfully applied to the determination of piroxicam in piroxicam preparations. The described method is also suitable to for analysies of serum samples with very small volumes and for pharmacokinetic studies.%建立了快速液相色谱-质谱/质谱联用法测定吡罗昔康制剂中吡罗昔康含量的方法.样品以0.1 moL/L盐酸甲醇溶液提取、微孔滤膜过滤、离心后,通过电喷雾离子化(ESI),采用多反应检测(MRM)方式进行正离子检测,用于定量分析的检测离子为m/z 332.2→94.8.采用Shim-pack XR-ODS (3.0 mm×75mm,2.0μm)柱分离,以乙腈-水-甲酸(60:40:0.1,V/V/V)为流动相,流速为0.40 mL/min,在3 min内完成吡罗昔康定量分析.线性范围为2.5~1000.0ng/mL,最低检测限为2.5 ng/mL;日内测

  3. Indirect flow-injection spectrophotometric determination of meloxicam, tenoxicam and piroxicam in pharmaceutical formulations.

    Science.gov (United States)

    Al-Momani, Idrees F

    2006-12-01

    A simple and sensitive indirect spectrophotometric method for the assay of meloxicam (MX), tenoxicam (TX) and piroxicam (PX) in pure and in pharmaceutical formulations by flow injection analysis (FIA) has been proposed. The method is based on the oxidation of these drugs by a known excess of N-bromosuccinimide (NBS) in an acidic medium, followed by a reaction of excess oxidant with chloranilic acid (CAA) to bleach its purple color. The absorbance values increased linearly with increasing concentrations of the drugs. Variables, such as the acidity, reagent concentrations, flow rate of reagents and other FI parameters were optimized to produce the most sensitive and reproducible results. The system obeyed Beer's low over concentration ranges of 10 - 160, 20 - 200 and 10 - 160 microg/ml for MX, TX and PX, respectively. The common excipients and additives did not interfere with their determinations. The method was successfully applied to the determinations of MX, TX and PX in various pharmaceutical preparations. The results obtained by the proposed method were found to be in good agreement with those found by the official HPLC methods.

  4. Ultrasensitive Determination of Piroxicam at Diflunisal-Derived Gold Nanoparticle-Modified Glassy Carbon Electrode

    Science.gov (United States)

    Shaikh, Tayyaba; uddin, SiraJ; Talpur, Farah N.; Khaskeli, Abdul R.; Agheem, Muhammad H.; Shah, Muhammad R.; Sherazi, Tufail H.; Siddiqui, Samia

    2017-10-01

    We present a simple and green approach for synthesis of gold nanoparticles (AuNps) using analgesic drug diflunisal (DF) as capping and stabilizing agent in aqueous solution. Characterization of the synthesized diflunisal-derived gold nanoparticles (DF-AuNps) was performed by ultraviolet-visible (UV-Vis) spectroscopy, revealing the surface plasmon absorption band at 520 nm under optimized experimental conditions. Fourier-transform infrared (FTIR) spectroscopy established the effective interaction of the capping agent with the AuNps. Topographical features of the synthesized DF-AuNps were assessed by atomic force microscopy (AFM), revealing average particle height of 29 nm to 32 nm. X-ray diffractometry was used to study the crystalline nature, revealing that the synthesized DF-AuNps possessed excellent crystalline properties. The synthesized DF-AuNps were employed to modify the surface of glassy carbon electrode (GCE) for selective determination of piroxicam (PX) using differential pulse voltammetry technique. The fabricated Nafion/DF-AuNps/GCE sensor exhibited high sensitivity compared with bare GCE. The current response of the fabricated sensor was found to be linear in the PX concentration range of 0.5 μM to 50 μM, with limit of detection (LOD) and limit of quantification (LOQ) of 50 nM and 150 nM, respectively. The proposed sensor was successfully utilized for sensitive and rapid determination of PX in human serum, urine, and pharmaceutical samples.

  5. Determination of piroxicam in pharmaceutical formulations and urine samples using europium-sensitized luminescence

    Energy Technology Data Exchange (ETDEWEB)

    Al-Kindy, Salma M.Z. [Department of Chemistry, College of Science, P.O. Box 36, Al-Khod 123, Sultan Qaboos University (Oman)], E-mail: alkindy@squ.edu.om; Suliman, Fakhr Eldin O.; Al-Wishahi, Aisha A.; Al-Lawati, Haidar A.J.; Aoudia, Muhammed [Department of Chemistry, College of Science, P.O. Box 36, Al-Khod 123, Sultan Qaboos University (Oman)

    2007-12-15

    A simple, selective and sensitive luminescence method for the assay of piroxicam (PX) in aqueous solution is developed. The method is based on the luminescence sensitization of europium (Eu{sup 3+}) by formation of ternary complex with PX in the presence of TOPO and Tween-80 as surfactant. The signal for Eu-PX-TOPO is monitored at {lambda}{sub ex}=359 nm and {lambda}{sub em}=615 nm. Optimum conditions for the formation of the complex in sequential injection analysis (SIA) were 0.01 M Tris buffer, pH 7.5, TOPO 5.0x10{sup -5} M, Tween-80 0.15% and 1.5 mM of Eu{sup 3+}, which allows the determination of 100-1000 ppb of PX with limit of detection (LOD) of 29 ppb. The relative standard deviations of the method range between 0.5% and 3.9% indicating excellent reproducibility of the method. The proposed method was successfully applied for the assay of PX in pharmaceutical formulations and in urine samples. Average recoveries of 100.8{+-}1.7% was obtained in tablet, whereas a recovery of 97.5{+-}2.0% was obtained for the total PX (PX+hydoxy-PX) in urine sample.

  6. Determination of piroxicam from rat articular tissue and plasma based on LC-MS/MS.

    Science.gov (United States)

    Kim, Han Sol; Cho, Ha Ra; Ho, Myoung Jin; Kang, Myung Joo; Choi, Yong Seok

    2016-12-01

    Osteoarthritis (OA) is the most common type of arthritis. To manage OA, in general, oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) is used. Recently, the analgesic and anti-inflammatory efficacy of piroxicam (PX), a long-acting NSAID, by intra-articular (IA) administration in OA was reported, and the possibility that PX is distributed in articular tissues at a certain concentration was raised. Thus, herein, novel LC-MS/MS methods to detect PX in rat articular tissue and plasma are presented. For articular tissue, solvent extraction with acetonitrile for 12 h was employed and a protein precipitation method was used for the preparation of a plasma sample. The developed methods were validated by following the FDA guidelines, and the validated methods were successfully applied to a PK study of IA PX. The present study presents, to our knowledge, the first method of determining a drug in articular tissue. Additionally, the level of PX in articular tissue after IA PX administration was experimentally confirmed for the first time using the present methods. Therefore, the present methods provide a new direction for in vivo evaluation for IA PX formulations and contribute to the development of alternative IA PX formulations with better effects for the treatment of OA.

  7. Inclusion of piroxicam in mesoporous phosphate glass-ceramic and evaluation of the physiochemical characteristics.

    Science.gov (United States)

    Javadzadeh, Yousef; Bairami Atashgah, Rahimeh; Barzegar-Jalali, Mohammad; Soleimani, Farshad; Mohammadi, Ghobad; Sabzevari, Araz; Adibkia, Khosro

    2014-04-01

    The mesoporous glass-ceramic (GC) was employed as a carrier to investigate its capability for pharmaceutical applications. Piroxicam (PX) as a model drug was loaded in the GC by using of solvent evaporation technique. The physicochemical properties and morphology of the powders were evaluated employing X-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). The drug adsorption isotherms were assessed as well. Drug release profiles were examined by fitting the data to the 10 common kinetic models. The specific surface area, Vm (the volume of the N2 adsorbed on the 1g of the GC when the monolayer is complete) and the average pore diameter of the GC powder before and after loading process were measured by the Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH) analysis benefiting N2 adsorption/desorption isotherms. The ideal loading of PX in the GC was 41.8%. The average pore diameter for the GC was determined to be about 10nm. The Freundlich model was found to be the best adsorption isotherm. Decrease of the GC specific surface area and Vm values were observed after loading process. Drug release data were best fitted to the Weibull model with the shape factor of 0.4-0.7 signifying the Fickian diffusion of PX from the GC. Accordingly, the GC could be considered as a suitable adsorbent to develop an oral drug delivery system.

  8. The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors.

    Science.gov (United States)

    Campione, Elena; Paternò, Evelin Jasmine; Candi, Eleonora; Falconi, Mattia; Costanza, Gaetana; Diluvio, Laura; Terrinoni, Alessandro; Bianchi, Luca; Orlandi, Augusto

    2015-01-01

    Piroxicam (PXM), a nonsteroidal anti-inflammatory drug, is an enolic benzothiazine and a potent member of the oxicam series. The drug suppresses the synthesis of proinflammatory enzymes, such as cyclo-oxygenases-1 and -2 (COX-1 and 2), downregulates the production of prostaglandins (PGs) and tromboxanes, and inhibits polyamines production by blocking ornithine decarboxylase induction involved in nonmelanoma skin carcinogenesis. In addition, PXM is able to induce tumor cell apoptosis and suppresses metalloproteinase 2 activities. Skin carcinogenesis is a multistep process in which the accumulation of genetic events leads to a gradually dysplastic cellular expression, deregulation of cell growth, and carcinomatous progression. COX-1 upregulation plays a significant role in PG and vascular epidermal growth factor production supporting tumor growth. Increased level of PGs in premalignant and/or malignant cutaneous tumors is also favored by upregulation of COX-2 and downregulation of the tumor suppressor gene 15-hydroxy-prostaglandin dehydrogenase. Chemoprevention can be a hopeful approach to inhibit carcinoma occurrence before an invasive tumor develops. The chemopreventive effect of nonsteroidal anti-inflammatory drugs on nonmelanoma skin cancers has been established. In this study, we highlighted the different modalities of action of PXM on the pathogenesis of nonmelanoma skin cancer, analyzing and evaluating binding modes and energies between COX-1 or COX-2 and PXM by protein-ligand molecular docking. Our clinical experience about the local use of PXM on actinic keratoses and field cancerization is also reported, confirming its efficacy as target therapy.

  9. Desarrollo y optimización de una jalea de piroxicam 0,5 %

    Directory of Open Access Journals (Sweden)

    Oscar García Pulpeiro

    Full Text Available Se desarrolló por primera vez en Cuba, una formulación de jalea de piroxicam al 0,5 %. Se tomó como referencia la composición de la formulación líder del mercado FELDENE GELâ, a la cual se le efectuaron algunas modificaciones. Se realizaron 4 experimentos en las evaluaciones preliminares que sirvieron de base para la etapa posterior de diseño y optimización de la formulación. Se aplicó un diseño de experimentos con mezcla, para lo cual se emplearon como variables independientes la concentración de Carbopol 940, trietanolamina y hidroxipropilmetilcelulosa. Se evaluó la influencia de estos componentes en el pH, el área de extensibilidad y en algunas propiedades organolépticas. A partir de estos resultados, se seleccionó una formulación óptima.

  10. A multiple unit floating drug delivery system of piroxicam using eudragit polymer

    Directory of Open Access Journals (Sweden)

    Kale R

    2007-01-01

    Full Text Available A floating drug delivery system of piroxicam in the form of microspheres was prepared using an enteric polymer and emulsification solvent-evaporation method. The microspheres remained buoyant continuously over the surface of acidic media containing surfactant for a period of 8-12 h in vitro . Differential scanning calorimetry and X-ray diffraction studies showed that drug incorporated in the outer shell of the polymer was completely amorphous. Scanning electron micrographs indicated that the microsphere is perfect sphere with an internal hollow cavity enclosed by a rigid shell of polymer. The micromeritic properties of microspheres were found to be much improved compared with original drug crystals. The in vitro drug release behavior of the floating microspheres was characterized as an enteric property. Polymer being soluble above pH 7.0, the drug release rates from microspheres changed dramatically above and below pH 7.0. At intestinal pH the drug release was faster and continuous as compared to the amount released at gastric pH.

  11. Comparison the Analgesic Effects of Single Dose Administration of Tramadol or Piroxicam on Postoperative Pain after Cesarean Delivery

    Directory of Open Access Journals (Sweden)

    Amir Farshchi

    2010-05-01

    Full Text Available "nA multimodal approach to postcesarean pain management may enhance analgesia and reduce side effects after surgery. We investigated postoperative pain in a double-blinded, randomized, single-dose comparison of the monoaminergic and µ-opioid agonist tramadol, 100 mg (Group T and piroxicam 20 mg (Group P given IM alone- single dose in 150 patients who had elective cesarean delivery. All patients were assessed at 0, 6, 12 and 24 hours post operation for pain degree (by Visual Analogue Score: VAS 1-10, nausea and vomiting. Pain degree was classified as: Painless: 0, Mild: 1-4, Moderate: 5-8, Severe: 9-10. There was no significant difference between the efficacy of tramadol and piroxicam injections (P>0.05. Pain intensity decreased markedly over time in both groups. Mean±SEM pain degrees were as follows: P=7.7±0.5, T=8.2±0.8 after 0 hours; P=5.4±0.6, T=6.1±0.5 after 6 hours; P=3.3±0.4, T=3.4±0.7 after 12 hours; P=1.1±0.4, T=1.3±0.5 after 24 hours of surgery. Side effects were similarly minimal with all treatments. It might be concluded that i.m. injections of 20 mg piroxicam (single dose therapy could relieve postoperative pain after cesarean section as well as tramadol and it could reduce opioid analgesic requirements with less adverse side effects during the first postoperative 24 h.

  12. Predictive validity and immune cell involvement in the pathogenesis of piroxicam-accelerated colitis in interleukin-10 knockout mice.

    Science.gov (United States)

    Holgersen, Kristine; Kvist, Peter Helding; Hansen, Axel Kornerup; Holm, Thomas Lindebo

    2014-07-01

    Piroxicam administration is a method for induction of enterocolitis in interleukin-10 knockout (IL-10 k.o.) mice. The piroxicam-accelerated colitis (PAC) IL-10 k.o. model combines a dysregulated immune response against the gut microbiota with a decreased mucosal integrity. The predictive validity and pathogenic mechanisms of the model have not been thoroughly investigated. In this study, IL-10 k.o. mice received piroxicam in the chow, and model qualification was performed by examining the efficacy of prophylactic anti-IL-12/23p40 monoclonal antibody (mAb), anti-TNFα mAb, cyclosporine A (CsA) and oral prednisolone treatment. To evaluate cell involvement in the disease pathogenesis, specific cell subsets were depleted by treatment with anti-CD4 mAb, anti-CD8 mAb or clodronate-encapsulated liposomes. T cell receptor co-stimulation was blocked by CTLA4-Ig. Cytokine profiling ELISAs and calprotectin immunohistochemistry were performed on colon tissue. Treatments with anti-IL-12/23p40 mAb and CsA prevented disease in PAC IL-10 k.o. mice and reduced IFNγ, IL-17A, MPO and calprotectin levels in colon. Anti-TNFα mAb treatment caused amelioration of selected clinical parameters. No effect of prednisolone was detected. Depletion of CD8(+) cells tended to increase mortality, whereas treatment with anti-CD4 mAb or CTLA4-Ig had no significant effect on disease development. Clodronate liposome treatment induced a loss of body weight; nevertheless macrophage depletion was associated with a significant reduction in colonic pathology. In conclusion, reference drugs with known efficacy in severe inflammatory bowel disease were efficacious in the PAC IL-10 k.o. model. Our data indicate that in this model macrophages are a main driver of colitis, whereas CD4(+) cells are not.

  13. Piroxicam fails to reduce myocellular enzyme leakage and delayed onset muscle soreness induced by isokinetic eccentric exercise

    Directory of Open Access Journals (Sweden)

    J-L. Croisier

    1996-01-01

    Full Text Available To test the hypothesis that delayed onset muscular soreness (DOMS following intense eccentric muscle contraction could be due to increased production of prostaglandin E2 (PGE2, ten healthy male subjects were studied. Using a double-blind randomized crossover design, each subject performed two isokinetic tests separated by a period of at least 6 weeks: once with placebo, and once with piroxicam (Feldene®. They were given one capsule containing either placebo or piroxicam (20 mg per day for 6 days with initial doses given starting 3 days prior to isokinetic testing. Exercise consisted of eight stages of five maximal contractions of the knee extensor and flexor muscle groups of both legs separated by 1 min rest phases, on a Kin Trex device at 60°/s angular velocity. The subjective presence and intensity of DOMS were evaluated using a visual analogue scale immediately after, and 24 and 48 h after each test. The mean plasma concentration of PGE2 measured at rest and after exercise was significantly lower in the group treated with piroxicam (p < 0.05. However, statistical analysis (two-way ANOVA test revealed that exercise did not cause any significant change of mean plasma PGE2 over time in either of the two groups. Eccentric work was followed by severe muscle pain in extensor and flexor muscle groups. Maximal soreness was noted 48 h postexercise. Serum creatine kinase activity and the serum concentration of myoglobin increased significantly, and reached peak values 48 h after exercise in both experimental conditions (p < 0.001. By paired t-test, it appeared that there were no significant differences in the serum levels of these two markers of muscle damage between the two groups at any time point. We conclude that: (1 oral administration of piroxicam fails to reduce muscle damage and DOMS caused by strenuous eccentric exercise; and (2 the hypothetical role of increased PGE2 production in eccentric exercise-induced muscle damage, DOMS, and reduced

  14. Spectrofluorimetric determination of 2-aminopyridine as a potential impurity in piroxicam and tenoxicam within the pharmacopoeial limit.

    Science.gov (United States)

    Barary, Magda H; Abdel-Hay, Mohamed H; Sabry, Suzy M; Belal, Tarek S

    2004-01-27

    The British Pharmacopoeia defines 2-aminopyridine (2-AP) as a potential impurity in piroxicam (PX) and tenoxicam (TX). Selective spectrofluorimetric determination of 2-AP in PX and TX, within or near the pharmacopoeial level, 0.2%, was developed, based on the measurement of the native fluorescence either in aqueous 0.1N sulfuric acid or in dioxane. Accordingly, this approach was followed for confirming purity of PX and TX in bulk and pharmaceutical preparations. The study was also extended to include simultaneous determinations of PX/2-AP and TX/2-AP systems based on selective fluorescence measurements in the cited solvents.

  15. Piroxicam fails to reduce myocellular enzyme leakage and delayed onset muscle soreness induced by isokinetic eccentric exercise

    Science.gov (United States)

    Croisier, J-L.; Monfils, T.; Deby-Dupon, G.; Fafchamps, M.; Venneman, I.; Crielaard, J-M.; Juchmès-Ferir, A.; Lhermerout, C.; Lamy, M.; Deby, C.

    1996-01-01

    To test the hypothesis that delayed onset muscular soreness (DOMS) following intense eccentric muscle contraction could be due to increased production of prostaglandin E2 (PGE2), ten healthy male subjects were studied. Using a double-blind randomized crossover design, each subject performed two isokinetic tests separated by a period of at least 6 weeks: once with placebo, and once with piroxicam (Feldene®). They were given one capsule containing either placebo or piroxicam (20 mg) per day for 6 days with initial doses given starting 3 days prior to isokinetic testing. Exercise consisted of eight stages of five maximal contractions of the knee extensor and flexor muscle groups of both legs separated by 1 min rest phases, on a Kin Trex device at 60°/s angular velocity. The subjective presence and intensity of DOMS were evaluated using a visual analogue scale immediately after, and 24 and 48 h after each test. The mean plasma concentration of PGE2 measured at rest and after exercise was significantly lower in the group treated with piroxicam (p < 0.05). However, statistical analysis (two-way ANOVA test) revealed that exercise did not cause any significant change of mean plasma PGE2 over time in either of the two groups. Eccentric work was followed by severe muscle pain in extensor and flexor muscle groups. Maximal soreness was noted 48 h postexercise. Serum creatine kinase activity and the serum concentration of myoglobin increased significantly, and reached peak values 48 h after exercise in both experimental conditions (p < 0.001). By paired t-test, it appeared that there were no significant differences in the serum levels of these two markers of muscle damage between the two groups at any time point. We conclude that: (1) oral administration of piroxicam fails to reduce muscle damage and DOMS caused by strenuous eccentric exercise; and (2) the hypothetical role of increased PGE2 production in eccentric exercise-induced muscle damage, DOMS, and reduced isokinetic

  16. Inhibition of matrix metalloproteinase-2 and 9 by Piroxicam confer neuroprotection in cerebral ischemia: an in silico evaluation of the hypothesis.

    Science.gov (United States)

    Mazumder, Muhammed Khairujjaman; Bhattacharya, Pallab; Borah, Anupom

    2014-12-01

    Matrix metalloproteinases are zinc-containing endopeptidases that are involved in extracellular matrix (ECM) remodeling cascade in many neurological disorders, including cerebral ischemia (CI). Remodeling of the ECM followed by disruption of the blood-brain barrier (BBB) is one of the major factors contributing to the ultimate neurodegeneration in CI. BBB disruption causes a cascade of pathophysiologies that trigger Anoikis-like cell death. While inhibition of MMP-2 and MMP-9 decreases the extent of neuronal damage in CI, MMP-2/9 knock-out mice have reduced infarct volume in experimental animal models of CI. Piroxicam, which is a non-steroidal anti-inflammatory drug (NSAID), has been demonstrated to be protective against aquaporin-4 and acid-sensing ion channel 1a--mediated neurodegeneration in CI. However, no report exists on the inhibitory action of Piroxicam on MMPs. We tested the hypothesis that Piroxicam, with its larger molecular size and more number of interacting pharmacophores, can inhibit MMP-2 and MMP-9. A comparative study on the inhibitory potential of Piroxicam with other reported MMP-inhibitors, viz., Aspirin, Melatonin and Doxycycline, has also been performed. Since the drug has already been reported to be neuroprotective through its inhibitory action in other pathways, it can be the drug of choice in the therapeutic management and prevention of neurodegeneration in CI.

  17. Application of Taguchi Method to Investigate the Effects of Process Factors on the Production of Industrial Piroxicam Polymorphs and Optimization of Dissolution Rate of Powder.

    Science.gov (United States)

    Shahbazian, Alen; Davood, Asghar; Dabirsiaghi, Alireza

    2016-01-01

    Piroxicam has two different crystalline forms (known as needle and cubic forms), that they are different in physicochemical properties such as biological solubility. In the current research, using Taguchi experimental design approach the influences of five operating variables on formation of the piroxicam polymorph shapes in recrystallization were studied. The variables include type of solvent, cooling methods, type of mixture paddle, pH, and agitator speed. Statistical analysis of results revealed the significance order of factors affecting the product quality and quantity. At first using the Taguchi experimental method, the influence of process factors on the yield, particle size and dissolution rate of piroxicam powder was statistically investigated. The optimum conditions to achieve the best dissolution rate of piroxicam were determined experimentally. The results were analyzed using Qualitek4 software and it was revealed that the type of solvent and method of cooling respectively are the most important factors that affect the dissolution rate. It was also experimentally achieved that some factors such as type of agitator paddle, pH and agitation rate have no significant effects on dissolution rate.

  18. Structure investigation, spectral, thermal, X-ray and mass characterization of piroxicam and its metal complexes

    Science.gov (United States)

    Zayed, M. A.; Nour El-Dien, F. A.; Mohamed, Gehad G.; El-Gamel, Nadia E. A.

    2004-10-01

    [M(H 2L) 2](A) 2. yH 2O (where H 2L: neutral piroxicam (Pir), A: Cl - in case of Ni(II) or acetate anion in case of Cu(II) and Zn(II) ions and y=0-2.5) and [M(H 2L) 3](A) z. yH 2O (A: SO 42- in case of Fe(II) ion ( z=1) or Cl - in case of Fe(III) ( z=3) and Co(II) ions ( z=2) and y=1-4) chelates are prepared and characterized using elemental analyses, IR, magnetic and electronic reflectance measurements, mass spectra and thermal analyses. IR spectra reveal that Pir behaves a neutral bidentate ligand coordinated to the metal ions through the pyridyl-N and carbonyl-O of the amide moiety. The reflectance and magnetic moment measurements reveal that these chelates have tetrahedral, square planar and octahedral geometrical structures. Mass spectra and thermal analyses are also used to confirm the proposed formulae and the possible fragments resulted from fragmentation of Pir and its chelates. The thermal behaviour of the chelates (TGA and DTA) are discussed in detail and the thermal stability of the anhydrous chelates follow the order Ni(II)≅Cu(II)

  19. Increased localized delivery of piroxicam by cationic nanoparticles after intra-articular injection

    Science.gov (United States)

    Kim, Sung Rae; Ho, Myoung Jin; Kim, Sang Hyun; Cho, Ha Ra; Kim, Han Sol; Choi, Yong Seok; Choi, Young Wook; Kang, Myung Joo

    2016-01-01

    Piroxicam (PRX), a potent nonsteroidal anti-inflammatory drug, is prescribed to relieve postoperative and/or chronic joint pain. However, its oral administration often results in serious gastrointestinal adverse effects including duodenal ulceration. Thus, a novel cationic nanoparticle (NP) was explored to minimize the systemic exposure and increase the retention time of PRX in the joint after intra-articular (IA) injection, by forming micrometer-sized electrostatic clusters with endogenous hyaluronic acid (HA) in the synovial cavity. PRX-loaded NPs consisting of poly(lactic-co-glycolic acid), Eudragit RL, and polyvinyl alcohol were constructed with the following characteristics: particle size of 220 nm, zeta potential of 11.5 mV in phosphate-buffered saline, and loading amount of 4.0% (w/w) of PRX. In optical and hyperspectral observations, the cationic NPs formed more than 50 μm-sized aggregates with HA, which was larger than the intercellular gaps between synoviocytes. In an in vivo pharmacokinetic study in rats, area under the plasma concentration–time curve (AUC0–24 h) and maximum plasma concentration (Cmax) of PRX after IA injection of the cationic NPs were <70% (P<0.05) and 60% (P<0.05), respectively, compared to those obtained from drug solution. Moreover, the drug concentration in joint tissue 24 h after dosing with the cationic NPs was 3.2-fold (P<0.05) and 1.8-fold (P<0.05) higher than that from drug solution and neutrally charged NPs, respectively. Therefore, we recommend the IA cationic NP therapy as an effective alternative to traditional oral therapy with PRX, as it increases drug retention selectively in the joint. PMID:27895468

  20. Synthesis of piroxicam loaded novel electrospun biodegradable nanocomposite scaffolds for periodontal regeneration.

    Science.gov (United States)

    Farooq, Ariba; Yar, Muhammad; Khan, Abdul Samad; Shahzadi, Lubna; Siddiqi, Saadat Anwar; Mahmood, Nasir; Rauf, Abdul; Qureshi, Zafar-ul-Ahsan; Manzoor, Faisal; Chaudhry, Aqif Anwar; ur Rehman, Ihtesham

    2015-11-01

    Development of biodegradable composites having the ability to suppress or eliminate the pathogenic micro-biota or modulate the inflammatory response has attracted great interest in order to limit/repair periodontal tissue destruction. The present report includes the development of non-steroidal anti-inflammatory drug encapsulated novel biodegradable chitosan (CS)/poly(vinyl alcohol) (PVA)/hydroxyapatite (HA) electro-spun (e-spun) composite nanofibrous mats and films and study of the effect of heat treatment on fibers and films morphology. It also describes comparative in-vitro drug release profiles from heat treated and control (non-heat treated) nanofibrous mats and films containing varying concentrations of piroxicam (PX). Electrospinning was used to obtain drug loaded ultrafine fibrous mats. The physical/chemical interactions were evaluated by Fourier Transform Infrared (FT-IR) spectroscopy. The morphology, structure and pore size of the materials were investigated by scanning electron microscopy (SEM). The thermal behavior of the materials was investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Control (not heat treated) and heat treated e-spun fibers mats and films were tested for in vitro drug release studies at physiological pH7.4 and initially, as per requirement burst release patterns were observed from both fibers and films and later sustained release profiles were noted. In vitro cytocompatibility was performed using VERO cell line of epithelial cells and all the synthesized materials were found to be non-cytotoxic. The current observations suggested that these materials are potential candidates for periodontal regeneration.

  1. Indirect spectrophotometric determination of piroxicam and tenoxicam through oxidation with potassium permanganate

    Directory of Open Access Journals (Sweden)

    A.S. Amin

    2010-04-01

    Full Text Available Three rapid, simple, accurate and selective validated spectrophtometric methods (A, B and C for the determination of piroxicam (PX and tenoxicam (TX in bulk sample and in dosage forms are described. The methods are based on the oxidation of the studied drugs by a known excess of potassium permanganate in sulfuric acid medium and subsequent determination of unreacted oxidant by reacting it with Methylene Blue (Basic Blue 9 dye (method A, Acid Red 27 (Amaranth dye (method B and Acid Orange 7 (orange II dye (method C, in the same medium at a suitable λmax = 660, 520 and 485 nm, respectively. The reacted oxidant was found to be corresponding to the drug content. Regression analysis of Beer-Lambert plots showed good correlations in the concentration ranges 1.0-8.0, 1.0-9.0 and 1.0-7.2 μg mL-1 using methods A, B and C, respectively, for PX and 0.3-7.0, 0.3-1.6 and 0.3-2.5 μg mL-1 using methods A, B and C, respectively, for TX. The stoichiometric ratios for the cited drugs to oxidant were studied. The optimum reaction conditions and other analytical parameters were evaluated. The proposed methods were applied successfully to determine the examined drugs either in pure form or pharmaceutical formulations with good accuracy and precision. The relative standard deviations were ≤ 0.33 with recoveries 98.9-101.7% for PX and ≤ 0.49 with recoveries 99.4-102.0% for TX.

  2. Solid-state, triboelectrostatic and dissolution characteristics of spray-dried piroxicam-glucosamine solid dispersions.

    Science.gov (United States)

    Adebisi, Adeola O; Kaialy, Waseem; Hussain, Tariq; Al-Hamidi, Hiba; Nokhodchi, Ali; Conway, Barbara R; Asare-Addo, Kofi

    2016-10-01

    This work explores the use of both spray drying and d-glucosamine HCl (GLU) as a hydrophilic carrier to improve the dissolution rate of piroxicam (PXM) whilst investigating the electrostatic charges associated with the spray drying process. Spray dried PXM:GLU solid dispersions were prepared and characterised (XRPD, DSC, SEM). Dissolution and triboelectric charging were also conducted. The results showed that the spray dried PXM alone, without GLU produced some PXM form II (DSC results) with no enhancement in solubility relative to that of the parent PXM. XRPD results also showed the spray drying process to decrease the crystallinity of GLU and solid dispersions produced. The presence of GLU improved the dissolution rate of PXM. Spray dried PXM: GLU at a ratio of 2:1 had the most improved dissolution. The spray drying process generally yielded PXM-GLU spherical particles of around 2.5μm which may have contributed to the improved dissolution. PXM showed a higher tendency for charging in comparison to the carrier GLU (-3.8 versus 0.5nC/g for untreated material and -7.5 versus 3.1nC/g for spray dried materials). Spray dried PXM and spray dried GLU demonstrated higher charge densities than untreated PXM and untreated GLU, respectively. Regardless of PXM:GLU ratio, all spray dried PXM:GLU solid dispersions showed a negligible charge density (net-CMR: 0.1-0.3nC/g). Spray drying of PXM:GLU solid dispersions can be used to produce formulation powders with practically no charge and thereby improving handling as well as dissolution behaviour of PXM.

  3. Synthesis of piroxicam loaded novel electrospun biodegradable nanocomposite scaffolds for periodontal regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Farooq, Ariba [Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Yar, Muhammad, E-mail: drmyar@ciitlahore.edu.pk [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Khan, Abdul Samad; Shahzadi, Lubna; Siddiqi, Saadat Anwar [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Mahmood, Nasir [Department of Allied Health Sciences and Chemical Pathology, University of Health Sciences, Lahore (Pakistan); Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore (Pakistan); Rauf, Abdul [Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Qureshi, Zafar-ul-Ahsan [Veterinary Research Institute, Lahore (Pakistan); Manzoor, Faisal; Chaudhry, Aqif Anwar [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Rehman, Ihtesham ur [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Department of Materials Science and Engineering, The Kroto Research Institute, The University of Sheffield, North Campus, Broad Lane, Sheffield S3 7HQ (United Kingdom)

    2015-11-01

    Development of biodegradable composites having the ability to suppress or eliminate the pathogenic micro-biota or modulate the inflammatory response has attracted great interest in order to limit/repair periodontal tissue destruction. The present report includes the development of non-steroidal anti-inflammatory drug encapsulated novel biodegradable chitosan (CS)/poly(vinyl alcohol) (PVA)/hydroxyapatite (HA) electro-spun (e-spun) composite nanofibrous mats and films and study of the effect of heat treatment on fibers and films morphology. It also describes comparative in-vitro drug release profiles from heat treated and control (non-heat treated) nanofibrous mats and films containing varying concentrations of piroxicam (PX). Electrospinning was used to obtain drug loaded ultrafine fibrous mats. The physical/chemical interactions were evaluated by Fourier Transform Infrared (FT-IR) spectroscopy. The morphology, structure and pore size of the materials were investigated by scanning electron microscopy (SEM). The thermal behavior of the materials was investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Control (not heat treated) and heat treated e-spun fibers mats and films were tested for in vitro drug release studies at physiological pH 7.4 and initially, as per requirement burst release patterns were observed from both fibers and films and later sustained release profiles were noted. In vitro cytocompatibility was performed using VERO cell line of epithelial cells and all the synthesized materials were found to be non-cytotoxic. The current observations suggested that these materials are potential candidates for periodontal regeneration. - Highlights: • Novel non-steroidal anti-inflammatory drug encapsulated biodegradable electrospun nanocomposite scaffolds were synthesized. • Heat treatment displayed great influence on the morphology of scaffolds. • Fiber diameter was decreased and pore size was increased after heat

  4. Piroxicam and intracavitary platinum-based chemotherapy for the treatment of advanced mesothelioma in pets: preliminary observations

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    Citro Gennaro

    2008-05-01

    Full Text Available Abstract Malignant Mesothelioma is an uncommon and very aggressive tumor that accounts for 1% of all the deaths secondary to malignancy in humans. Interestingly, this neoplasm has been occasionally described in companion animals as well. Aim of this study was the preclinical evaluation of the combination of piroxicam with platinum-based intracavitary chemotherapy in pets. Three companion animals have been treated in a three years period with this combination. Diagnosis was obtained by ultrasonographic exam of the body cavities that evidenced thickening of the mesothelium. A surgical biopsy further substantiated the diagnosis. After drainage of the malignant effusion from the affected cavity, the patients received four cycles of intracavitary CDDP at the dose of 50 mg/m2 every three weeks if dogs or four cycles of intracavitary carboplatin at the dose of 180 mg/m2 (every 3 weeks if cats, coupled with daily administration of piroxicam at the dose of 0.3 mg/kg. The therapy was able to arrest the effusion in all patients for variable remission times: one dog is still in remission after 3 years, one dog died of progressive disease after 8 months and one cat died due to progressive neoplastic growth after six months, when the patient developed a mesothelial cuirass. The combination showed remarkable efficacy at controlling the malignant effusion secondary to MM in our patients and warrants further investigations.

  5. Does Piroxicam really protect ischemic neurons and influence neuronal firing in cerebral ischemia? An exploration towards therapeutics.

    Science.gov (United States)

    Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana

    2013-09-01

    Cerebral ischemia is still one of the most confusing and enigmatic neurological disorders with least understood injuries. The EEG measures have been traditionally used to detect residual neural dysfunctions after cerebral ischemia although having several shortcomings, yielding controversial and inconsistent results. It is feasible to hypothesize that advanced EEG research can overcome these shortcomings and provide more clear information regarding the long lasting neural impairment in the subjects suffered from brain stroke. To our understanding, EEG power spectrum density measures can significantly contribute towards intervening drug administered diseased model and give us correct status of neuronal firing after an insult. On the basis of our findings we hypothesize that Piroxicam, a non-steroidal anti-inflammatory drug (NSAID) can protect neurons and improves neuronal firing after ischemia/reperfusion injury in animal model of focal cerebral ischemia. This is the first ever finding which advocates the role of Piroxicam, a NSAID in neuronal firing apart from its other neuroprotective roles. Thus, we consider the possibility of modulation of neuronal firing as a therapeutic strategy to help prevent neuronal dysfunctions in cerebral ischemia.

  6. The piroxicam complex of copper(II), trans-[Cu(Pir)2(THF)2], and its interaction with DNA

    Science.gov (United States)

    Hadadzadeh, Hassan; Salimi, Mona; Weil, Matthias; Jannesari, Zahra; Darabi, Farivash; Abdi, Khatereh; Khalaji, Aliakbar Dehno; Sardari, Soroush; Ahangari, Reza

    2012-08-01

    The mononuclear Cu(II) complex, trans-[Cu(Pir)2(THF)2], where Pir is 4-hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (piroxicam), has been prepared and characterized by elemental analysis, spectroscopic methods (UV-Vis, IR, and 1H NMR) and single crystal X-ray structure analysis. The molecular structure of the centrosymmetric complex is made up of two monoanionic bidentate Pir ligands coordinated to the Cu(II) atom through the pyridyl N atom and the carbonyl O atom of the amide group in equatorial positions. The elongated rhombic octahedral (ERO) coordination of the CuNONOO2″ chromophore is completed by the O atoms of two THF molecules in axial positions. A strong intramolecular hydrogen bond between the amide N-H function and the enolate O atom confirms the ZZZ conformation of piroxicam. In addition, CD spectroscopy and gel electrophoresis assays have been used to investigate the interaction of the complex with DNA. The results revealed that the binding of the complex with DNA led to DNA backbone distortion.

  7. Systematic Development of Transethosomal Gel System of Piroxicam: Formulation Optimization, In Vitro Evaluation, and Ex Vivo Assessment.

    Science.gov (United States)

    Garg, Varun; Singh, Harmanpreet; Bhatia, Amit; Raza, Kaisar; Singh, Sachin Kumar; Singh, Bhupinder; Beg, Sarwar

    2017-01-01

    Piroxicam is used in the treatment of rheumatoid arthritis, osteoarthritis, and other inflammatory diseases. Upon oral administration, it is reported to cause ulcerative colitis, gastrointestinal irritation, edema and peptic ulcer. Hence, an alternative delivery system has been designed in the form of transethosome. The present study describes the preparation, optimization, characterization, and ex vivo study of piroxicam-loaded transethosomal gel using the central composite design. On the basis of the prescreening study, the concentration of lipids and ethanol was kept in the range of 2-4% w/v and 0-40% v/v, respectively. Formulation was optimized by measuring drug retention in the skin, drug permeation, entrapment efficiency, and vesicle size. Optimized formulation was incorporated in hydrogel and compared with other analogous vesicular (liposomes, ethosomes, and transfersomes) gels for the aforementioned responses. Among the various lipids used, soya phosphatidylcholine (SPL 70) and ethanol in various percentages were found to affect drug retention in the skin, drug permeation, vesicle size, and entrapment efficiency. The optimized batch of transethosome has shown 392.730 μg cm(-2) drug retention in the skin, 44.312 μg cm(-2) h(-1) drug permeation, 68.434% entrapment efficiency, and 655.369 nm vesicle size, respectively. It was observed that the developed transethosomes were found superior in all the responses as compared to other vesicular formulations with improved stability and highest elasticity. Similar observations were noted with its gel formulation.

  8. Development and in vitro evaluation of an enteric-coated multiparticulate drug delivery system for the administration of piroxicam to dogs.

    Science.gov (United States)

    Debunne, Ann; Vervaet, Chris; Remon, Jean Paul

    2002-11-01

    The aim of the study was to develop enteric-coated pellets for the administration of piroxicam (a poorly water-soluble drug) to small animals in order to avoid local gastrointestinal irritation, one of the major side effects of nonsteroidal anti-inflammatory drugs after oral ingestion. Pellets were made by an extrusion-spheronization process. The influence of several excipients on the in vitro drug release was evaluated. Piroxicam release from the uncoated pellets was measured in phosphate buffer (pH 6.8) using the paddle dissolution method (USP XXIII). The enteric-coated pellets were tested in 0.1 N HCl and phosphate buffer, pH 6.8. The addition of sodium croscarmellose (Ac-Di-Sol) did not influence the piroxicam release from microcrystalline cellulose pellets. Sodium carboxymethyl starch (Explotab) increased the release from 30 to 65% at 45 min. The incorporation of sodium carboxymethyl cellulose on its own or as a co-processed blend with microcrystalline cellulose (Avicel RC 581 and CL 611) enhanced the release of piroxicam at 45 min from 30% (pure Avicel PH 101) to 95% (combination of Avicel PH 101 and CL 611 in a ratio of 1:3). Additional use of cyclodextrins had only a minor influence on the dissolution rate. An Eudragit L 30 D-55 and FS 30 D (6/4) film was applied to the core pellets (containing 2.5% (w/w) piroxicam and a combination of Avicel PH 101 and CL 611 in a ratio of 1:3) in order to obtain gastroresistant properties. The coated pellets retained their dissolution characteristics after compression into fast disintegrating tablets because waxy cushioning beads were added to minimize film damage.

  9. Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with CYP2C8*3 and CYP2C9

    Directory of Open Access Journals (Sweden)

    Calvo AM

    2017-07-01

    Full Text Available Adriana Maria Calvo, Paulo Zupelari-Gonçalves, Thiago José Dionísio, Daniel Thomas Brozoski, Flávio Augusto Faria, Carlos Ferreira Santos Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, São Paulo, Brazil Objective: Nonsteroidal anti-inflammatory drugs (NSAIDs are metabolized by the cytochrome P450 enzymes (CYPs, predominantly CYP2C8 and CYP2C9. The aim of this study was to evaluate the possible association of polymorphisms in the CYP2C8*3 and CYP2C9 genes with the clinical efficacy of oral piroxicam (20 mg daily for 4 days after lower third molar surgeries with regard to postoperative pain, swelling, trismus, adverse reactions, need for rescue medication and the volunteer’s overall satisfaction. Materials and methods: For this purpose, 102 volunteers were genotyped for CYP2C8*3 and CYP2C9 polymorphisms. Briefly, genomic DNA was isolated from saliva collected from volunteers subjected to invasive lower third molar surgeries, and the preoperative, intraoperative and postoperative parameters were collected and analyzed. Results: An equal amount of piroxicam sufficiently managed postoperative pain and inflammatory symptoms, with visual analog pain scores typically <40 mm for all genotypes investigated. Furthermore, only two out of 102 volunteers heterozygous for CYP2C8*3 and CYP2C9*3 reported adverse side effects. Conclusion: In general, slow metabolizers of piroxicam, who were volunteers with mutant alleles, were indifferent from normal metabolizers with the wild-type alleles and therefore did not require specialized piroxicam doses to manage postoperative pain and inflammation. Keywords: piroxicam, lower third molar surgery, P450, CYP2C8, CYP2C9, pharmacogenetics 

  10. The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors

    Directory of Open Access Journals (Sweden)

    Campione E

    2015-10-01

    Full Text Available Elena Campione,1 Evelin Jasmine Paternò,2 Eleonora Candi,3,4 Mattia Falconi,5 Gaetana Costanza,2 Laura Diluvio,1 Alessandro Terrinoni,4 Luca Bianchi,1 Augusto Orlandi2,6,7 1Department of Dermatology, 2Department of Biomedicine and Prevention, 3Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, 4Biochemistry Laboratory IDI-IRCCS, Faculty of Medicine, University of Rome “Tor Vergata”, 5Department of Biology, University of Rome “Tor Vergata”, 6Institute of Anatomic Pathology, University of Rome “Tor Vergata”, 7Tor Vergata University-Policlinic of Rome, Rome, Italy Abstract: Piroxicam (PXM, a nonsteroidal anti-inflammatory drug, is an enolic benzothiazine and a potent member of the oxicam series. The drug suppresses the synthesis of proinflammatory enzymes, such as cyclooxygenases-1 and -2 (COX-1 and 2, downregulates the production of prostaglandins (PGs and tromboxanes, and inhibits polyamines production by blocking ornithine decarboxylase induction involved in nonmelanoma skin carcinogenesis. In addition, PXM is able to induce tumor cell apoptosis and suppresses metalloproteinase 2 activities. Skin carcinogenesis is a multistep process in which the accumulation of genetic events leads to a gradually dysplastic cellular expression, deregulation of cell growth, and carcinomatous progression. COX-1 upregulation plays a significant role in PG and vascular epidermal growth factor production supporting tumor growth. Increased level of PGs in premalignant and/or malignant cutaneous tumors is also favored by upregulation of COX-2 and downregulation of the tumor suppressor gene 15-hydroxy-prostaglandin dehydrogenase. Chemoprevention can be a hopeful approach to inhibit carcinoma occurrence before an invasive tumor develops. The chemopreventive effect of nonsteroidal anti-inflammatory drugs on nonmelanoma skin cancers has been established. In this study, we highlighted the different modalities of action

  11. Transbuccal permeation, anti-inflammatory activity and clinical efficacy of piroxicam formulated in different gels.

    Science.gov (United States)

    Attia, M A; El-Gibaly, I; Shaltout, S E; Fetih, G N

    2004-05-19

    In attempts to avoid the systemic side effects of piroxicam (PC) (e.g. gastrotoxicity), several buccal gel formulations containing PC were prepared and their effects on the characteristics of the drug permeation through rabbit buccal mucosa in-vitro were evaluated using a Franz-type diffusion cell. The general rank order of the total flux of 0.5% PC from gels was found to be: hydroxypropylmethylcellulose (HPMC, 2.5%) > hydroxypropylcellulose (HPC, 2.5%) >or= sodium alginate (Na alg., 7%) > methylcellulose (MC, 3%) > hydroxyethylcellulose (HEC, 1.5%) > carbopol 934 (Carb. 934, 1%) >or= sodium carboxymethylcellulose (NaCMC, 2%) > pluronic F-127 (PF-127, 20%) > polyvinyl alcohol (PVA, 10%). The effect of various penetration enhancers 1% sodium lauryl sulphate (NaLS), 3% sodium deoxycholate (NaDC), 3% sodium tauroglycocholate (NaTGC) on the rate of permeation across the excised buccal mucosa (of 0.5% PC in gels prepared using 3% MC, 2.5% HPMC or 7% Na alg. base) and histology of the buccal epithelium was also investigated. Pharmacodynamic evaluation of the anti-inflammatory activity of PC in these gel formulations (containing 3% NaDC as an enhancer) was carried out using the kaolin-induced rat paw oedema method. The results obtained indicated that PC administered in 7% Na alg. or 2.5% HPMC gel bases was significantly more effective than the 3% MC gel and oral drug solution in suppressing oedema formation in rats. Comparative clinical studies were conducted in patients with post-operative dental pain and oedema following maxillofacial operations. The results revealed that 7% Na alg. and 2.5% HPMC gel formulations applied to the buccal mucosa were slightly better than or equally effective to the orally administered commercial product (Feldene Flash) tablet) in reducing pain level, swelling and tenderness within a period of 4 days. These findings suggest that PC (0.5%) administered in the buccal gel may present a potential therapeutical use as a strong anti

  12. Mechanical Anisotropy and Pressure Induced Structural Changes in Piroxicam Crystals Probed by In Situ Indentation and Raman Spectroscopy

    Science.gov (United States)

    Manimunda, Praveena; Hintsala, Eric; Asif, Syed; Mishra, Manish Kumar

    2017-01-01

    The ability to correlate mechanical and chemical characterization techniques in real time is both lacking and powerful tool for gaining insights into material behavior. This is demonstrated through use of a novel nanoindentation device equipped with Raman spectroscopy to explore the deformation-induced structural changes in piroxicam crystals. Mechanical anisotropy was observed in two major faces ( 0bar{1}1 ) and (011), which are correlated to changes in the interlayer interaction from in situ Raman spectra recorded during indentation. The results of this study demonstrate the considerable potential of an in situ Raman nanoindentation instrument for studying a variety of topics, including stress-induced phase transformation mechanisms, mechanochemistry, and solid state reactivity under mechanical forces that occur in molecular and pharmaceutical solids.

  13. Femtosecond dynamics of a non-steroidal anti-inflammatory drug (piroxicam) in solution: The involvement of twisting motion

    Science.gov (United States)

    Gil, Michał; Douhal, Abderrazzak

    2008-06-01

    In this contribution, we report on fast and ultrafast dynamics of a non-steroidal anti-inflammatory drug, piroxicam (PX), in methyl acetate (MAC) and triacetin (TAC), two solvents of different viscosities. The enol form of PX undergoes a femtosecond (shorter than 100 fs) electronically excited state intramolecular proton-transfer reaction to produce keto tautomers. These structures exhibit an internal twisting motion to generate keto rotamers in ˜2-5 ps, a time being longer in TAC. The transient absorption/emission spectrum is very broad indicating that the potential-energy surface at the electronically excited state is very flat, and reflecting the involvement of several coordinates along which the wavepacket of the fs-produced structures evolve.

  14. Determination of piroxicam in pharmaceutical preparations by ultraviolet direct spectrophotometry, ultraviolet difference spectrophotometry and high performance liquid chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Hackmann, E.R.M.; Santos Gianotto, E.A. dos; Miritello Santoro, M.I.R. (Universidade de Sao Paulo (Brazil))

    1993-02-01

    Piroxicam in pharmaceutical preparations (capsules (C), tablets (T), oral drops (OD), suppositories (S) and simulated sample (SS)) was determined by UV direct spectrophotometry (UVS) at 333 nm, by UV difference spectrophotometry (UVDS) at 327 nm, and in C and T, by high performance liquid chromatography (HPLC). For UVS, Beer's law was obeyed in the range 3.0-8.5 [mu]g/mL. The coefficient of correlation (CC), absolute precision (AP) and relative precision (RP) were 0.9999, 0.02 and 0.33%, respectively. The coefficient of variation (CV) for C, T, OD, S and SS were 0.48%, 0.35%, 0.48% and 0.19%, respectively. The recovery average (RA) was 100.22%. For UVDS, Beer's law was obeyed in the range 5.0-15.0 [mu]g/mL. The CC, AP and RP were respectively 0.9999, 0.05 and 0.47%. The CV for C, T, OD, S and SS were 0.64%, 0.84%, 0.62%, 0.54% and 0.15%, respectively. The RA was 99.02%. In HPLC determination, a LiChrospher[reg sign] 100 RP-18 (5 [mu]m) in LiChroCART[reg sign] 125-4 column at ambient temperature with a mobile phase consisting of methanol: (buffer solution citric acid-dibasic sodium phosphate pH 3.0) (55:45) and UV detection at 254 nm enabled the determination of piroxicam in C and T. The response peak area versus concentration presented linearity in the range 10.0-100.0 [mu]g/mL. The CC, AP and RP were 0.9997, 0.45 and 0.90%, respectively. The CV was 0.51%-0.82% and the RA, 97.13%. 14 refs., 1 fig., 5 tabs.

  15. Evaluation and enhancement of physical stability of semi-solid dispersions containing piroxicam into hard gelatin capsules.

    Science.gov (United States)

    Karataş, Ayşegül; Bekmezci, Serife

    2013-01-01

    The aim of the study was to investigate the physical stability of the semi-solid dispersions into the hard gelatine capsules prepared with Gelucire 44/14, Labrasol and different additives such as microcrystalline cellulose (MCC), mannitol and lactose (alpha-monohydrate) used for enhancing the stability of the formulations. The master dispersion prepared with only Gelucire 44/14 (20% w/w) and Labrasol (80% w/w) was stored in a refrigerator (5 +/- 3 degrees C), while the modified dispersions with the additives (2% w/w) were kept in a climatic chamber (25 +/- 2 degrees C / 60 +/- 5% RH) for 12 months. Dissolution tests of the semi-solid dispersions were performed in media with different pH's immediatly after preparation and after 3, 6 and 12 months of storage. FTIR and DSC studies were also carried out at the same time points. The ideal storage condition for the master dispersion was found to be at 5 degrees C. The addition of MCC, mannitol and lactose (alpha-monohydrate) to the original dispersion afforded a solidification effect on the formulation at room temperature and showed the same dissolution behavior (not less than 85% of piroxicam within 30 min in pH 1.2, 4.5 and 6.8; and water) with the master. The dispersion including lactose was stable at 25 degrees C for 12 months. However, the ideal period of storage for the modified dispersions including MCC and mannitol was 6 months at 25 degrees C. FTIR and DSC results both confirmed the amorphous state of piroxicam in all semi-solid dispersions under storage conditions for 12 months.

  16. A novel extraction technique based on carbon nanotubes reinforced hollow fiber solid/liquid microextraction for the measurement of piroxicam and diclofenac combined with high performance liquid chromatography.

    Science.gov (United States)

    Song, Xin-Yue; Shi, Yan-Ping; Chen, Juan

    2012-10-15

    A novel design of carbon nanotubes reinforced hollow fiber solid/liquid phase microextraction (CNTs-HF-SLPME) was developed to determine piroxicam and diclofenac in different real water samples. Functionalized multi-walled carbon nanotubes (MWCNTs) were held in the pores of hollow fiber with sol-gel technology. The pores and lumen of carbon nanotubes reinforced hollow fiber were subsequently filled with a μL volume of organic solvent (1-octanol), and then the whole assembly was used for the extraction of the target analytes in direct immersion sampling mode. The target analytes were extracted from the sample by two extractants, one of which is organic solvent placed inside the pores and lumen of hollow fiber and the other one is CNTs held in the pores of hollow fiber. After extraction, the analytes were desorbed in acetonitrile and analyzed using high performance liquid chromatography. This novel extraction mode showed more excellent extraction performance in comparison with conventional hollow fiber liquid microextraction (without adding CNTs) and carbon nanotubes reinforced hollow fiber solid microextraction (CNTs held in the pores of hollow fiber, but no organic solvents placed inside the lumen of hollow fiber) under the respective optimum conditions. This method provided 47- and 184-fold enrichment factors for piroxicam and diclofenac, respectively, good inter-fiber repeatability and batch-to-batch reproducibility. Linearity was observed in the range of 20-960 μg L(-1) for piroxicam, and 10-2560 μg L(-1) for diclofenac, with correlation coefficients of 0.9985 and 0.9989, respectively. The limits of detection were 4.58 μg L(-1) for piroxicam and 0.40 μg L(-1) for diclofenac.

  17. Crystal structure of a 2:1 piroxicam–gentisic acid co-crystal featuring neutral and zwitterionic piroxicam mol­ecules

    Science.gov (United States)

    Horstman, Elizabeth M.; Bertke, Jeffery A.; Woods, Toby J.; Kenis, Paul J. A.

    2016-01-01

    A new 2:1 co-crystal of piroxicam and gentisic acid [systematic name: 4-hy­droxy-1,1-dioxo-N-(pyridin-2-yl)-2H-1λ6,2-benzo­thia­zine-3-carboxamide–2-(4-oxido-1,1-dioxo-2H-1λ6,2-benzo­thia­zine-3-amido)­pyridin-1-ium–2,5-di­hydroxy­benzoic acid, 2C15H13N3O4S·C7H6O4] has been synthesized using a microfluidic platform and initially identified using Raman spectroscopy. In the co-crystal, one piroxicam mol­ecule is in its neutral form and an intra­molecular O—H⋯O hydrogen bond is observed. The other piroxicam mol­ecule is zwitterionic (proton transfer from the OH group to the pyridine N atom) and two intra­molecular N—H⋯O hydrogen bonds occur. The gentisic acid mol­ecule shows whole-mol­ecule disorder over two sets of sites in a 0.809 (2):0.191 (2) ratio. In the crystal, extensive hydrogen bonding between the components forms layers propagating in the ab plane. PMID:27980814

  18. Safety evaluation of combination toceranib phosphate (Palladia®) and piroxicam in tumour-bearing dogs (excluding mast cell tumours): a phase I dose-finding study.

    Science.gov (United States)

    Chon, E; McCartan, L; Kubicek, L N; Vail, D M

    2012-09-01

    Toceranib phosphate and piroxicam have individually demonstrated antineoplastic activity. Additionally, non-steroidal anti-inflammatory therapy is often warranted in aged cancer-bearing dogs for management of osteoarthritis comorbidity. As concurrent use may be warranted for a given individual and the adverse event (AE) profile for each can be overlapping (gastrointestinal), a phase I trial was performed in tumour-bearing (non-mast cell) dogs to establish the safety of the combination using a standard 3+3 cohort design. Five dose-escalating cohorts, up to and including approved label dosage for toceranib and standard dosage for piroxicam, were completed without observing a frequency of dose-limiting AEs necessitating cohort closure. Therefore, the combination of standard dosages of both drugs (toceranib, 3.25 mg kg(-1), every other day; piroxicam, 0.3 mg kg(-1) daily) is generally safe. Several antitumour responses were observed. As with single-agent toceranib, label-indicated treatment holidays and dose reductions (e.g. 2.5-2.75 mg kg(-1)) may occasionally be required owing to gastrointestinal events.

  19. Comparative study of the safety and efficacy of ebrotidine versus ranitidine and placebo in the prevention of piroxicam-induced gastroduodenal lesions.

    Science.gov (United States)

    Puscas, I; Puscas, C; Coltau, M; Pasca, R; Torres, J; Márquez, M; Herrero, E; Fillat, O; Ortiz, J A

    1997-04-01

    This study assessed the efficacy of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) versus ranitidine and placebo in preventing gastroduodenal lesions induced by piroxicam. Thirty patients with rheumatic disease, who were divided into 5 groups, received an oral treatment of piroxicam 20 mg once daily for 6 days plus ebrotidine 400 mg/day (Group I); ebrotidine 800 mg/day (Group II); ranitidine 150 mg/day (Group III); ranitidine 300 mg/day (Group IV); or placebo (Group V). Patients were endoscopically examined before and after treatment. Lanza's score was also determined, and laboratory tests were performed. The results of this study showed that the most powerful protective effect against mucosal gastric lesions induced by piroxicam was achieved with 800 mg/day of ebrotidine. Ranitidine at doses of 150 mg/day did not protect gastric mucosa, and the 300 mg/day dose exerted a poor gastroprotective effect.

  20. Immunomodulatory effect of NSAID in geriatric patients with acute infection: effects of piroxicam on chemokine/cytokine secretion patterns and levels of heat shock proteins. A double-blind randomized controlled trial. (ISRCTN58517443).

    Science.gov (United States)

    Beyer, Ingo; Njemini, Rose; Bautmans, Ivan; Demanet, Christian; Mets, Tony

    2012-03-01

    Inflammation in older persons is associated with frailty, cachexia, and disability. We hypothesized that NSAID treatment in addition to antibiotics in older patients with acute infection might rapidly reduce inflammatory cytokines and might be of therapeutic potential to improve outcomes. A double-blind controlled trial was conducted in geriatric patients admitted for acute infection. Patients were randomized to receive either 10 mg piroxicam or placebo. Patients ≥70 years with CRP levels >10 mg/L of acute infectious origin were eligible. Twenty-five cyto-/chemokines as well as heat shock proteins Hsp27 (HSPB1) and Hsp70 (HSPA1A) were measured the first 4 days and then weekly until discharge, with a maximum of 3 weeks. Thirty Caucasian patients were included (median age 84.5 years, 67% female, median CRP 87.5 mg/L). In the piroxicam group, IL-6 and IP-10/CXCL10 decreased significantly during the study period. Relationships between cytokines were disrupted in the piroxicam group: for 12 out of 20 cytokines the number of correlations between changes in serum levels was significantly lower compared to placebo. Serum Hsp70 levels decreased significantly in the piroxicam group, but not in the placebo group. Without heat challenge, intracellular levels of Hsp70 in monocytes decreased in both groups, whereas HsP27 in monocytes increased with piroxicam with a significant difference compared to placebo at 3 weeks. Piroxicam in this setting cannot be considered merely as an anti-inflammatory drug, but rather as an immunomodulator. Further studies are needed to establish whether these effects can change functional outcomes in geriatric patients.

  1. Direct evaluation of molecular States of piroxicam/poloxamer nanosuspension by suspended-state NMR and Raman spectroscopies.

    Science.gov (United States)

    Hasegawa, Yuki; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

    2015-05-04

    A nanosuspension of piroxicam (PXC) and poloxamer 407 (poloxamer) prepared by the wet milling method was directly evaluated at the molecular level from the viewpoint of both solution and solid phases. (13)C solution-state NMR measurements revealed a reduction in the concentration of dissolved poloxamer in the nanosuspension. Furthermore, the fraction of dissolved poly(ethylene oxide) (PEO) chain, which is the hydrophilic part of poloxamer, was higher than that of dissolved poly(propylene oxide) (PPO) chain, the hydrophobic part. (13)C suspended-state NMR and Raman spectroscopies detected both solid-state PXC and poloxamer involved in the nanoparticles. Interestingly, the coexistence of crystalline and amorphous PXC in the nanoparticle was demonstrated. The yellow color of the nanosuspension strongly supported the existence of amorphous PXC. Changes in the peak intensity depending on the contact time in the suspended-state NMR spectrum revealed that the PEO chain of poloxamer in the nanoparticle had higher mobility compared with the PPO chain. The PEO chain should project into the water phase and form the outer layer of the nanoparticles, whereas the PPO chain should face the inner side of the nanoparticles. Amorphous PXC could be stabilized by intermolecular interaction with the PPO chain near the surface of the nanoparticles, whereas crystalline PXC could form the inner core.

  2. Colon specific CODES based Piroxicam tablet for colon targeting: statistical optimization, in vivo roentgenography and stability assessment.

    Science.gov (United States)

    Singh, Amit Kumar; Pathak, Kamla

    2015-03-01

    This study was aimed to statistically optimize CODES™ based Piroxicam (PXM) tablet for colon targeting. A 3(2) full factorial design was used for preparation of core tablet that was subsequently coated to get CODES™ based tablet. The experimental design of core tablets comprised of two independent variables: amount of lactulose and PEG 6000, each at three different levels and the dependent variable was %CDR at 12 h. The core tablets were evaluated for pharmacopoeial and non-pharmacopoeial test and coated with optimized levels of Eudragit E100 followed by HPMC K15 and finally with Eudragit S100. The in vitro drug release study of F1-F9 was carried out by change over media method (0.1 N HCl buffer, pH 1.2, phosphate buffer, pH 7.4 and phosphate buffer, pH 6.8 with enzyme β-galactosidase 120 IU) to select optimized formulation F9 that was subjected to in vivo roentgenography. Roentgenography study corroborated the in vitro performance, thus providing the proof of concept. The experimental design was validated by extra check point formulation and Diffuse Reflectance Spectroscopy revealed absence of any interaction between drug and formulation excipients. The shelf life of F9 was deduced as 12 months. Conclusively, colon targeted CODES™ technology based PXM tablets were successfully optimized and its potential of colon targeting was validated by roentgenography.

  3. Towards improved solubility of poorly water-soluble drugs: cryogenic co-grinding of piroxicam with carrier polymers.

    Science.gov (United States)

    Penkina, Anna; Semjonov, Kristian; Hakola, Maija; Vuorinen, Sirpa; Repo, Timo; Yliruusi, Jouko; Aruväli, Jaan; Kogermann, Karin; Veski, Peep; Heinämäki, Jyrki

    2016-01-01

    Amorphous solid dispersions (SDs) open up exciting opportunities in formulating poorly water-soluble active pharmaceutical ingredients (APIs). In the present study, novel catalytic pretreated softwood cellulose (CPSC) and polyvinylpyrrolidone (PVP) were investigated as carrier polymers for preparing and stabilizing cryogenic co-ground SDs of poorly water-soluble piroxicam (PRX). CPSC was isolated from pine wood (Pinus sylvestris). Raman and Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used for characterizing the solid-state changes and drug-polymer interactions. High-resolution scanning electron microscope (SEM) was used to analyze the particle size and surface morphology of starting materials and final cryogenic co-ground SDs. In addition, the molecular aspects of drug-polymer interactions and stabilization mechanisms are presented. The results showed that the carrier polymer influenced both the degree of amorphization of PRX and stabilization against crystallization. The cryogenic co-ground SDs prepared from PVP showed an enhanced dissolution rate of PRX, while the corresponding SDs prepared from CPSC exhibited a clear sustained release behavior. In conclusion, cryogenic co-grinding provides a versatile method for preparing amorphous SDs of poorly water-soluble APIs. The solid-state stability and dissolution behavior of such co-ground SDs are to a great extent dependent on the carrier polymer used.

  4. Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study.

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    Cheryl A London

    Full Text Available We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI and overall survival (OS in dogs with appendicular osteosarcoma (OSA following amputation and carboplatin chemotherapy.This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126 received carboplatin chemotherapy (4 doses following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8 were removed from the study for therapy-associated adverse events compared to control dogs (n = 1. The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274; the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08. The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib.The addition of toceranib to metronomic

  5. Effects of D-002, a product isolated from beeswax, on gastric symptoms of patients with osteoarthritis treated with piroxicam: a pilot study.

    Science.gov (United States)

    Illnait, José; Terry, Héctor; Más, Rosa; Fernández, Lilia; Carbajal, D

    2005-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are indicated for treatment of rheumatoid arthritis and osteoarthritis, but often induce gastric adverse experiences (AE), including gastric ulcers and complications. Inhibitors of proton pump and H(2) antagonists are very effective for duodenal ulcer; meanwhile, cytoprotective drugs are more effective for gastric ulcer. D-002 is a mixture of higher aliphatic alcohols obtained from beeswax, wherein triacontanol is the most abundant. D-002 induces anti-ulcer effects through a cytoprotective mechanism, being more effective in protecting against ethanol- and NSAID-induced ulcers. The present double-blind, placebo-controlled clinical study was undertaken to investigate the effects of D-002 on gastric symptoms associated to piroxicam use on patients suffering osteoarthritis. Fifty-nine patients, all taking piroxicam, 20 mg/day, were randomized to placebo or D-002 (40 or 100 mg/day) for 14 days. The primary efficacy variable was the reduction on the frequency of patients with gastric AE compared with placebo. Pain evolution was investigated to discard any influence on D-002 on the analgesic effect of piroxicam. The frequency of patients treated with D-002, 40 and 100 mg/day, reporting acidity [0 of 18 (0%) and 1 of 21 (4.8%), respectively] was lower (P < .05) than in placebo [6 of 20 (30%)]. Also, the frequency of patients treated with 100 mg/day reporting some gastric AE [5 of 21 (23.8%)] was lower (P < .05) than in placebo [13 of 20 (65.0%)]. The analgesic effect of piroxicam was unaffected with D-002. Treatment was well tolerated. Two patients discontinued from the study because of gastrointestinal AE: one in the placebo group and the other treated with D-002, 40 mg/day. Other three patients discontinued because of other AE: mildly uncontrolled hypertension (one in the placebo group, one treated with D-002, 40 mg/day) and headache (one treated with D-200, 100 mg/day). It is concluded that D-002 could be useful for

  6. Differential modulation of transforming growth factor-betas and cyclooxygenases in the platelet lysates of male F344 rats by dietary lipids and piroxicam.

    Science.gov (United States)

    Raju, Jayadev; Bird, Ranjana P

    2002-02-01

    Platelets are implicated in the pathogenesis of various chronic diseases including cancer. The main objective of the present study was to determine if dietary fish oil and piroxicam, known modulators of colon tumorigenesis, effect transforming growth factor (TGF)-betas and cyclooxygenase (COX) isozymes in the platelets of colon tumor-bearing male F344 rats. TGF-betas and COXs are important in the development of chronic illnesses including colon cancer. Animals harboring preneoplastic colonic lesions were randomly allocated to a low fat diet (5% by weight--low corn oil, LFC) and three high fat diets (23% by weight--high corn oil, HFC; high corn oil containing 150-ppm piroxicam, HFC+P; and high fish oil, HFF) for 16 weeks. TGF-beta1, TGF-beta2, COX-1 and COX-2 protein levels were assessed in the platelets by Western blot analysis. Active TGF-beta1 (12.5 kDa) level was significantly lower in the platelets of the HFC+P group (p level was significantly lower in the platelets of the HFF group (p protein in the platelets. However a 29-kDa protein, potentially a precursor of TGF-beta2, was detected in the platelets of all the groups and was significantly lower in the HFC+P and HFF groups than in LFC and HFC (p level was significantly lower in the HFF group than the other three groups (p protein was detected in the platelets of all diet groups. Piroxicam in the presence of high corn oil (HFC+P) significantly lowered the level of COX-2 (p level. These findings conclusively show that LFC and HFC differ from HFF and HFC+P, and piroxicam differs from fish oil, in regulating the levels of TGF-betas and COX in the platelets. This supports the conjecture that the levels of bioactive constituents of the platelets are profoundly modulated by dietary lipids, which in turn could influence the pathogenesis of chronic illnesses.

  7. Preparo e caracterização de micropartículas de acetobutirato de celulose e poli(3-hidroxibutirato contendo piroxicam - DOI: 10.4025/actascihealthsci.v31i1.4428 Preparation and characterization of cellulose acetate butyrate and poly(3-hydroxybutyrate microparticles containing piroxicam - DOI: 10.4025/actascihealthsci.v31i1.4428

    Directory of Open Access Journals (Sweden)

    Melissa Zétola

    2009-05-01

    Full Text Available O objetivo deste trabalho foi avaliar a influência da massa molar do acetobutirato de celulose (ABC e da adição de poli(3-hidroxibutirato [PHB] sobre a morfologia das micropartículas, a eficiência de encapsulação e os perfis de liberação do piroxicam. As micropartículas foram preparadas por meio da técnica de emulsão/evaporação do solvente O/A e caracterizadas quanto à morfologia por microscopia eletrônica de varredura. O teor de fármaco nas micropartículas foi determinado utilizando o método de espectrofotometria de absorção na região do ultravioleta; os ensaios de liberação realizados, utilizando tampão fosfato pH 6,8. As micropartículas obtidas apresentaram formas irregulares, e aquelas preparadas a partir do ABC com maior massa molar apresentaram maior tamanho. Mediante planejamento fatorial, observou-se que as variáveis analisadas (massa molar do ABC e adição de PHB não influenciaram a eficiência de encapsulação do piroxicam, mas exerceram influência sobre a quantidade inicial de piroxicam liberada a partir das micropartículas.This work aims to evaluate the influence of the cellulose acetate butyrate (CAB molar weight and the addition of poly(3-hydroxybutyrate [PHB] on microparticle morphology, encapsulation efficiency and release profile of piroxicam. The microparticles were prepared using the O/W emulsion/solvent evaporation technique and characterized according to the morphology using scanning electron microscopy. The drug content in the microparticles was determined through UV spectrophotometry and a dissolution assay was conducted using phosphate buffer pH 6.8. The obtained microparticles presented irregular shape; the ones prepared with CAB with large molar weight presented a larger size. Through a factorial design, it was observed that the analyzed variables (CAB molar weight and PHB addition did not influence the encapsulation efficiency, but did influence the initial release of piroxicam from the

  8. Piroxicam inhibits NMDA receptor-mediated excitotoxicity through allosteric inhibition of the GluN2B subunit: an in silico study elucidating a novel mechanism of action of the drug.

    Science.gov (United States)

    Mazumder, Muhammed Khairujjaman; Borah, Anupom

    2014-12-01

    Hyperactivation of GluN2B subunit containing N-methyl-d-aspartate receptors (NMDARs) significantly contributes to the development of several neurodegenerative diseases through a process called excitotoxicity. NMDARs are voltage-gated Ca2+ channels which when activated lead to excessive influx of Ca2+ into neurons thereby exacerbating several calcium-dependent pathways that cause oxidative stress and apoptosis. Several drugs are presently in use to counter the NMDAR-mediated excitotoxic events among which Ifenprodil and its derivatives are GluN2B selective allosteric antagonists. Certain non-steroidal anti-inflammatory drugs (NSAIDs) have also been reported to inhibit NMDARs and the resultant pathologies. Meanwhile, Piroxicam, which is a NSAID, has been reported to be protective in cerebral ischemia-induced neurodegeneration through various pathways. Since Piroxicam has more number of interacting groups as compared to other NSAIDs and also has structural similarities with Ifenprodil, we thought it prudent that Piroxicam may inhibit NMDARs similar to Ifenprodil. By using molecular docking as a tool, we validated the hypothesis and hereby report for the first time that Piroxicam can inhibit GluN2B containing NMDARs through allosteric mode similar to the well known selective antagonist--Ifenprodil; and thus can be a therapeutic drug for the prevention of excitotoxic neurodegeneration.

  9. Analysis of Piroxicam in Pharmaceutical Formulation and Human Urine by Dispersive Liquid–Liquid Microextraction Combined with Spectrophotometry

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    Nakisa Seyyedeh Tutunchi

    2013-02-01

    Full Text Available Purpose: Piroxicam, is non–steroidal anti–inflammatory and analgesic agent, which is widely used in the treatment of patients with rheumatologic disorders. A new analytical approach based on the dispersive liquid–liquid microextraction (DLLME has been developed for the extraction and determination of PX in pharmaceutical preparation and human urine. Methods: From the PX standard solution or solutions prepared from real samples, aliquot volumes were pipetted into centrifuge tubes and mixed with acetate buffer at pH 3.0 and NaCl solution. The contents were subjected to the DLLME, so 700 μL of methanol containing 70 μL of chloroform was injected rapidly into a sample solution. A cloudy solution was rapidly produced and the PX extracted into dispersed fine droplets. The mixture was centrifuged, thus these fine droplets of chloroform were settled. The supernatant aqueous phase was readily decanted, then the remained organic phase was diluted with ethanol and the absorbance measured at 355 ± 3 nm against a reagent blank. Results: The main factors affecting the extraction efficiency such as pH, extraction and disperser solvent types and etc. were studied and optimized systematically. Under optimized conditions, the calibration graphs were linear over the range of 0.2 to 4.8 μg/mL. The limit of detection and relative standard deviation were found to be 0.058 μg/mL and 2.83%, respectively. Relative recoveries in the spiked samples ranged from 97 to 110%. Conclusion: Using the developed method PX can be analyzed in pharmaceutical formulation and human urine sample in a simpler, cheaper and more rapid manner.

  10. Analysis of Piroxicam in Pharmaceutical Formulation and Human Urine by Dispersive Liquid–Liquid Microextraction Combined with Spectrophotometry

    Science.gov (United States)

    Bavili Tabrizi, Ahad; Seyyedeh Tutunchi, Nakisa

    2013-01-01

    Purpose: Piroxicam, is non–steroidal anti–inflammatory and analgesic agent, which is widely used in the treatment of patients with rheumatologic disorders. A new analytical approach based on the dispersive liquid–liquid microextraction (DLLME) has been developed for the extraction and determination of PX in pharmaceutical preparation and human urine. Methods: From the PX standard solution or solutions prepared from real samples, aliquot volumes were pipetted into centrifuge tubes and mixed with acetate buffer at pH 3.0 and NaCl solution. The contents were subjected to the DLLME, so 700 µL of methanol containing 70 µL of chloroform was injected rapidly into a sample solution. A cloudy solution was rapidly produced and the PX extracted into dispersed fine droplets. The mixture was centrifuged, thus these fine droplets of chloroform were settled. The supernatant aqueous phase was readily decanted, then the remained organic phase was diluted with ethanol and the absorbance measured at 355 ± 3 nm against a reagent blank. Results: The main factors affecting the extraction efficiency such as pH, extraction and disperser solvent types and etc. were studied and optimized systematically. Under optimized conditions, the calibration graphs were linear over the range of 0.2 to 4.8 µg/mL. The limit of detection and relative standard deviation were found to be 0.058 µg/mL and 2.83%, respectively. Relative recoveries in the spiked samples ranged from 97 to 110%. Conclusion: Using the developed method PX can be analyzed in pharmaceutical formulation and human urine sample in a simpler, cheaper and more rapid manner. PMID:24312810

  11. Ethyl cellulose nanoparticles as a platform to decrease ulcerogenic potential of piroxicam: formulation and in vitro/in vivo evaluation

    Science.gov (United States)

    El-Habashy, Salma E; Allam, Ahmed N; El-Kamel, Amal H

    2016-01-01

    Nanoparticles (NPs) have long gained significant interest for their use in various drug formulations in order to increase bioavailability, prolong drug release, and decrease side effects of highly toxic drugs. The objective of this investigation was to evaluate the potential of ethyl cellulose-based NPs (EC-NPs) to modulate the release and reduce ulcerogenicity of piroxicam (PX) after oral administration. PX-loaded EC-NPs were prepared by solvent evaporation technique using different stabilizers at three concentration levels. Morphological examination of selected formulas confirmed the formation of spherical NPs with slightly porous surface. Formulation containing poloxamer-stabilized EC-NPs (P188/0.2), having a particle size of 240.26±29.24 nm, polydispersity index of 0.562±0.030, entrapment efficiency of 85.29%±1.57%, and modulated release of PX (88% after 12 hours), was selected as the optimum formulation. Differential scanning calorimetry demonstrated the presence of PX in an amorphous form in the NPs. Fourier-transform infrared spectroscopy revealed the possible formation of hydrogen bond and the absence of chemical interaction. In vivo study, evaluation of pharmacokinetic parameters, evaluation of gastric irritation potential, and histological examination were conducted after administration of the selected formulation. Time to reach maximum plasma concentration, tmax, of poloxamer-stabilized EC-NPs was significantly higher than that of Feldene® 20 mg capsules (P≤0.001). Encapsulation of the acidic, gastric offender PX into NPs managed to significantly suppress gastric ulceration potential in rats (P≤0.05) as compared to that of PX suspension. A reduction of 66% in mean ulcer index was observed. In conclusion, poloxamer-stabilized EC-NPs (P188/0.2) had a significant potential of offsetting deleterious side effects common in PX use. PMID:27307735

  12. Vibrational spectra (FT-IR, FT-Raman), frontier molecular orbital, first hyperpolarizability, NBO analysis and thermodynamics properties of Piroxicam by HF and DFT methods.

    Science.gov (United States)

    Suresh, S; Gunasekaran, S; Srinivasan, S

    2015-03-05

    The solid phase FT-IR and FT-Raman spectra of 4-Hydroxy-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (Piroxicam) have been recorded in the region 4000-400 and 4000-100cm(-1) respectively. The molecular geometry, harmonic vibrational frequencies and bonding features of piroxicam in the ground state have been calculated by Hartree-Fock (HF) and density functional theory (DFT) methods using 6-311++G(d,p) basis set. The calculated harmonic vibrational frequencies are scaled and they are compared with experimental obtained by FT-IR and FT-Raman spectra. A detailed interpretation of the vibrational spectra of the title compound has been made on the basis of the calculated potential energy distribution (PED). The electronic properties, such as HOMO and LUMO energies, molecular electrostatic potential (MESP) are also performed. The linear polarizability (α) and the first order hyper polarizability (β) values of the title compound have been computed. The molecular stability arising from hyper conjugative interaction, charge delocalization has been analyzed using natural bond orbital (NBO) analysis.

  13. Vibrational spectra (FT-IR, FT-Raman), frontier molecular orbital, first hyperpolarizability, NBO analysis and thermodynamics properties of Piroxicam by HF and DFT methods

    Science.gov (United States)

    Suresh, S.; Gunasekaran, S.; Srinivasan, S.

    2015-03-01

    The solid phase FT-IR and FT-Raman spectra of 4-Hydroxy-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (Piroxicam) have been recorded in the region 4000-400 and 4000-100 cm-1 respectively. The molecular geometry, harmonic vibrational frequencies and bonding features of piroxicam in the ground state have been calculated by Hartree-Fock (HF) and density functional theory (DFT) methods using 6-311++G(d,p) basis set. The calculated harmonic vibrational frequencies are scaled and they are compared with experimental obtained by FT-IR and FT-Raman spectra. A detailed interpretation of the vibrational spectra of the title compound has been made on the basis of the calculated potential energy distribution (PED). The electronic properties, such as HOMO and LUMO energies, molecular electrostatic potential (MESP) are also performed. The linear polarizability (α) and the first order hyper polarizability (β) values of the title compound have been computed. The molecular stability arising from hyper conjugative interaction, charge delocalization has been analyzed using natural bond orbital (NBO) analysis.

  14. Pharmacokinetic Study of Piroxicam Patches in Rats%吡罗昔康贴片在大鼠体内的药代动力学研究

    Institute of Scientific and Technical Information of China (English)

    杨媛; 胡晓

    2012-01-01

    目的 通过研究吡罗昔康在大鼠体内的药代动力学过程及其分布特点,探索其经皮给药系统的药物转运特性.方法 高效液相色谱法(HPLC)测定吡罗昔康经皮给药后不同时间点大鼠血浆、关节中吡罗昔康的浓度;大鼠右肩部应用2、4、6 mg吡罗昔康贴片后,用DAS软件处理时间-血药浓度数据,计算药代动力学参数.结果 大鼠局部给药4 mg后2、4、8h,关节中吡罗昔康质量分数分别为:(119±26)、(1 538±358)、(1 349±320)ng·g-1,血浆中呲罗昔康质量浓度分别为:(427±82)、(2 015±184)、(1 317±224)μg·L-1,它们的比值介于0.28和1.02之间;在2~6 mg剂量范围内,大鼠局部应用吡罗昔康贴片,血浆中吡罗昔康质量浓度4h达峰值,药峰质量浓度(Cmax)分别为:(925±118)、(1 980±135)、(2 644±337)μg·L-1,药时曲线下面积(AUC0-∞)分别为:(29 976±10 845)、(63 871±58 534)、(85 389±15 352)μg·L-1· h-1,Cmax、AUC0-∞随剂量的增高成比例增大.结论 吡罗昔康经皮给药后,可直接从用药部位渗透至局部深层的关节组织中并达到较高的质量浓度;在2~6 mg内,吡罗昔康贴片于大鼠体内呈线性动力学特征.%Objective To investigate the drug transport of transdermal delivery of piroxicam through observing its pharmacokinetic process and distribution characteristics. Methods Three doses of piroxicam (2,4 and 6 mg) were administered to right shoulders of rats. The concentrations of piroxicam in plasma and joint fluid were determined by high-pressure liquid chromatogra-phy(HPLC) and pharmacokinetic parameters were calculated by DAS 1. 0 software. Results At 2,4 and 6 hours after topical application of 4 mg piroxicam,the drug concentrations were (427 ± 82), (2 015 ±184) and (1 317±224)μg o L-1 in plasma, and (119±26),(1 538±358) and (1 349±320)ng o g-1in joint fluid,respectively. The ratio of joint fluid to plasma in piroxicam concentrations ranged from 0. 28 to 1. 02. The

  15. Ethyl cellulose nanoparticles as a platform to decrease ulcerogenic potential of piroxicam: formulation and in vitro/in vivo evaluation

    Directory of Open Access Journals (Sweden)

    El-Habashy SE

    2016-05-01

    Full Text Available Salma E El-Habashy, Ahmed N Allam, Amal H El-Kamel Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt Abstract: Nanoparticles (NPs have long gained significant interest for their use in various drug formulations in order to increase bioavailability, prolong drug release, and decrease side effects of highly toxic drugs. The objective of this investigation was to evaluate the potential of ethyl cellulose-based NPs (EC-NPs to modulate the release and reduce ulcerogenicity of piroxicam (PX after oral administration. PX-loaded EC-NPs were prepared by solvent evaporation technique using different stabilizers at three concentration levels. Morphological examination of selected formulas confirmed the formation of spherical NPs with slightly porous surface. Formulation containing poloxamer-stabilized EC-NPs (P188/0.2, having a particle size of 240.26±29.24 nm, polydispersity index of 0.562±0.030, entrapment efficiency of 85.29%±1.57%, and modulated release of PX (88% after 12 hours, was selected as the optimum formulation. Differential scanning calorimetry demonstrated the presence of PX in an amorphous form in the NPs. Fourier-transform infrared spectroscopy revealed the possible formation of hydrogen bond and the absence of chemical interaction. In vivo study, evaluation of pharmacokinetic parameters, evaluation of gastric irritation potential, and histological examination were conducted after administration of the selected formulation. Time to reach maximum plasma concentration, tmax, of poloxamer-stabilized EC-NPs was significantly higher than that of Feldene® 20 mg capsules (P≤0.001. Encapsulation of the acidic, gastric offender PX into NPs managed to significantly suppress gastric ulceration potential in rats (P≤0.05 as compared to that of PX suspension. A reduction of 66% in mean ulcer index was observed. In conclusion, poloxamer-stabilized EC-NPs (P188/0.2 had a significant potential of

  16. 高效液相色谱法测定铌罗昔康片的含量%Determination of Piroxicam Tablets by High Performance Liquid Chromatography

    Institute of Scientific and Technical Information of China (English)

    张宏祥; 刘燕

    2011-01-01

    Objective: A method determining the piroxicam tablets is explored.Methods: GL Sciences Inertsil ODSSP(5μm, 250×4.6mm)column was used.The mobile phase was acetonitrile - phosphate buffer solution (disodium hydrogen phosphate 7.15g, dissolved in water into 1000mL, adjusted with 20% citric acid solution, pH 5.0) (40:60).The detection wavelength was 358nm.The column temperature was 35℃ and the flow rate was 1.0mL·min-1.Results: Piroxicam in the 21.26 ~ 106.30 mg·L-1 within the sample volume and the peak area showed good linearity (r = 0.9999).The average recovery rate was 99.68%(n=6), and RSD was 0.88%.Conclusion: The determination of piroxicam tablets by HPLC is specific,accurate and reliable.%目的探讨吡罗昔康片含量测定的方法.方法采用GL Sciences Inertsil ODS-SP(5μm,250x4.6mm)色谱柱,以乙腈-磷酸盐缓冲液(取磷酸氮二钠7.15g,加水溶解成1OOOML,用20%柠檬酸溶液调节PH值为5.0)(40:60)为流动相,检测波长为358nm,柱温为35℃,流速为1.OmL.min-1.结果吡罗昔康在21.26~106.30 mg.L-1,范围内进样量与峰面积呈良好线性关系(r=0.9999),平均回收率为99.68% (n=6),RSD为0.88%.结论HPLC法测定吡罗昔康片的含量,专属性强,结果准确可靠.

  17. A mononuclear zinc(II) complex with piroxicam: crystal structure, DNA- and BSA-binding studies; in vitro cell cytotoxicity and molecular modeling of oxicam complexes.

    Science.gov (United States)

    Jannesari, Zahra; Hadadzadeh, Hassan; Amirghofran, Zahra; Simpson, Jim; Khayamian, Taghi; Maleki, Batool

    2015-02-05

    A new mononuclear Zn(II) complex, trans-[Zn(Pir)2(DMSO)2], where Pir(-) is 4-hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (piroxicam), has been synthesized and characterized. The crystal structure of the complex was obtained by the single crystal X-ray diffraction technique. The interaction of the complex with DNA and BSA was investigated. The complex interacts with FS-DNA by two binding modes, viz., electrostatic and groove binding (major and minor). The microenvironment and the secondary structure of BSA are changed in the presence of the complex. The anticancer effects of the seven complexes of oxicam family were also determined on the human K562 cell lines and the results showed reasonable cytotoxicities. The interactions of the oxicam complexes with BSA and DNA were modeled by molecular docking and molecular dynamic simulation methods.

  18. A mononuclear zinc(II) complex with piroxicam: Crystal structure, DNA- and BSA-binding studies; in vitro cell cytotoxicity and molecular modeling of oxicam complexes

    Science.gov (United States)

    Jannesari, Zahra; Hadadzadeh, Hassan; Amirghofran, Zahra; Simpson, Jim; Khayamian, Taghi; Maleki, Batool

    2015-02-01

    A new mononuclear Zn(II) complex, trans-[Zn(Pir)2(DMSO)2], where Pir- is 4-hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (piroxicam), has been synthesized and characterized. The crystal structure of the complex was obtained by the single crystal X-ray diffraction technique. The interaction of the complex with DNA and BSA was investigated. The complex interacts with FS-DNA by two binding modes, viz., electrostatic and groove binding (major and minor). The microenvironment and the secondary structure of BSA are changed in the presence of the complex. The anticancer effects of the seven complexes of oxicam family were also determined on the human K562 cell lines and the results showed reasonable cytotoxicities. The interactions of the oxicam complexes with BSA and DNA were modeled by molecular docking and molecular dynamic simulation methods.

  19. 顶空气相色谱法测定吡罗昔康原料药有机溶剂残留量%Determination of residual by headspace gas chromatography organic solvents in piroxicam

    Institute of Scientific and Technical Information of China (English)

    李育; 赵靖霞; 杨根金; 董昕; 李玲; 苏笠; 张薇

    2011-01-01

    Objective To establish a headspace capillary gas chromatgraphy for determination the residual organic solvents in piroxicam. Methods The residual solvents in piroxicam which are methanol , ethanol, toluene and dimethybenzene were determined by headspace GC on HP-INNOWax column(30 m ×0. 32 mm × 0. 25 μm) ,with FID detector, high purity nitrogen as the carry gas. Results Four residual organic solvents consisting of methanol, ethanol, toluene and dimethybenzene in piroxicam were completely separated and the samples coincided with the requirements. Conclusion The method is sensitive and accurate. It is suitable to the determination of residual organic solvents in piroxicam.%目的 建立吡罗昔康原料药中有机溶剂残留量的气相色谱测定法.方法 采用顶空气相色谱,使用HP-INNO-WAX毛细管色谱柱(30 m×0.32 mm×0.25 μm);以高纯氮气为载气,FID为检测器,测定吡罗昔康原料药中甲醇、乙醇、甲苯及二甲苯4种有机溶剂的残留量.结果 4种有机溶剂均达到了完全分离,在所考察范围内线性关系良好.结论 该方法 灵敏度、准确度均达到有机溶剂残留量的检测要求,适用于吡罗昔康原料药中有机溶剂残留的检测.

  20. Enhancing Percutaneous Permeability of Piroxicam through Rat Skin by Essential Oil from Cyperus rotundus L.%香附挥发油对吡罗昔康体外促透皮作用研究

    Institute of Scientific and Technical Information of China (English)

    韩艳; 田亚珍; 覃华; 杜小燕; 王庆伟

    2012-01-01

    Objective To study the effects of essential oil from Cyperus rolundus L. on percutaneous permeability of piroxicam through rat shin in vitro, and provide the basis for screening penetration enhancers form traditional Chinese medicine and developing the transdermal formulation of piroxicam. Method Transdermal test was performed by the modified Franz diffusion cell in vitro and the cumulative permeation content of piroxicam was determined by HPLC. Results A good percutaneous permeability was obtained when the essential oil from Cyperus rotundus L. was more than 1%. The Cumulative permeation amount and the enhanced permeability factors of piroxicam with 5% Cyperus rotundus volatile oil and 5% azone were (188. 9 ± 19. 62)μg/cm2、(268.4 ±28. 81)μg/cm2 and 6. 156、6. 611. Conclusion The essential oil from Cyperus rotundus L. shows strong penetration enhancing effect for piroxicam.%目的 考察香附挥发油对吡罗昔康体外经SD大鼠皮渗透的影响,为开发中药透皮促进剂和吡罗昔康经皮渗透剂提供依据.方法 用改良的Franz扩散池进行体外透皮实验,HPLC法测定吡罗昔康含量.结果 浓度大于1%的香附挥发油,对吡罗昔康具有良好的促渗透作用.吡罗昔康中加入5%香附挥发油、5%氮酮后的累积渗透量及增渗倍数分别为(188.9±19.62) μg/cm2、(268.4±28.81) μg/cm2和6.156、6.611.结论 香附挥发油对吡罗昔康的体外渗透作用具有明显的促进作用.

  1. The influence of piroxicam, a non-selective cyclooxygenase inhibitor, on autonomic nervous system activity in experimental cyclophosphamide-induced hemorrhagic cystitis and bladder outlet obstruction in rats.

    Science.gov (United States)

    Dobrek, Łukasz; Baranowska, Agnieszka; Skowron, Beata; Thor, Piotr J

    2014-01-01

    Signs and symptoms of secondary overactive bladder (OAB) are observed both in course of infravesical obstruction of urine outflow in patients with benign prostatic hyperplasia, and as a result of development of hemorrhagic cystitis (HC) following administration of cyclophosphamide (CP). Non-steroidal antiinflammatory drugs (NSAIDs) alleviate symptoms of bladder overactivity reducing local synthesis of prostaglandins (PGs), but precise effects of those agents on functions of the autonomic nervous system (ANS) in course of OAB remain unknown. The purpose of this study was to evaluate the effect of piroxicam-induced prostaglandins (PGs) synthesis block on activity of the ANS in two experimental models of secondary OAB: bladder outlet obstruction (BOO) and cyclophosphamide-induced HC (CP-HC), by heart rate variability analysis (HRV). The experiment was performed on a group of rats with surgically induced 2-week BOO, and on a group of rats that were administered CP five times, with corresponding control groups. Study animals were given piroxicam (PRX) i.p. in two doses: 2 and 10 mg/kg b.w. In the BOO model, PRX in both doses revealed a trend for reduction of value of all non-normalized components of HRV. The lower PRX dose caused an increased nHF value, and PRX administered in the dose of 10 mg/kg b.w. caused an increase of the nLF value. In the CP-HC model, the lower PRX dose caused a trend for an increase of values of all non-normalized components, and the higher dose--for their decrease. Both doses of PRX in that model caused increase of the nLF value. Inhibition of PGs synthesis caused changes of ANS function in both models of OAB. Both in BOO and in CP-HC, PGs seem to be ANS-activating factors, responsible for maintenance of a high parasympathetic activity. In both models, inhibition of PGs synthesis with PRX administered at the dose of 10 mg/kg b.w. lead to functional reconstruction of ANS, with marked sympathetic predominance. That may contribute to reduction of

  2. Quantitative Analysis of Piroxicam Using Temperature-Controlled Ionic Liquid Dispersive Liquid Phase Microextraction Followed By Stopped-Flow Injection Spectrofluorimetry

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Ganjali

    2013-07-01

    Full Text Available Background:Piroxicam (PXM belongs to the wide class of non-steroidal anti-inflammatory drugs (NSAIDs. PXM has been widely applied in the treatment of rheumatoid arthritis, gonarthrosis, osteoarthritis, backaches, neuralgia, mialgia. In the presented work, a green and benign sample pretreatment method called temperature-controlled ionic liquid dispersive liquid phase microextraction (TCIL-DLPME was followed with stopped-flow injection spectrofluorimetry (SFIS for quantitation of PXM in pharmaceutical formulations and biological samples.Methods:Temperature-controlled ionic liquid dispersive liquid phase microextraction (TCIL-DLPME was applied as an environmentally friendly sample enrichment method to extract and isolate PXM prior to quantitation. Dispersion of 1-hexyl-3-methylimidazolium hexafluorophosphate ([Hmim][PF6] ionic liquid (IL through the sample aqueous solution was performed by applying a relatively high temperature. PXM was extracted into the extractor, and after phase separation, PXM in the final solution was determined by stopped-flow injection spectrofluorimetry (SFIS.Results and Major Conclusion:Different factors affecting the designed method such as IL amount, diluting agent, pH and temperature were investigated in details and optimized. The method provided a linear dynamic range of 0.2-150 μg l-1, a limit of detection (LOD of 0.046 μg l-1 and a relative standard deviation (RSD of 3.1%. Furthermore, in order to demonstrate the analytical applicability of the recommended method, it was applied for quantitation of PXM in real samples.

  3. Sensitive and selective spectrophotometric assay of piroxicam in pure form, capsule and human blood serum samples via ion-pair complex formation.

    Science.gov (United States)

    Alizadeh, Nina; Keyhanian, Fereshteh

    2014-09-15

    A simple, accurate and highly sensitive spectrophotometric method has been developed for the rapid determination of piroxicam (PX) in pure and pharmaceutical formulations. The proposed method involves formation of stable yellow colored ion-pair complexes of the amino derivative (basic nitrogen) of PX with three sulphonphthalein acid dyes namely; bromocresol green (BCG), bromothymol blue (BTB), bromophenol blue (BPB) in acidic medium. The colored species exhibited absorption maxima at 438, 429 and 432 nm with molar absorptivity values of 9.400×10(3), 1.218×10(3) and 1.02×10(4) L mol(-1) cm(-1) for PX-BCG, PX-BTB and PX-BPB complexes, respectively. The effect of optimum conditions via acidity, reagent concentration, time and solvent were studied. The reactions were extremely rapid at room temperature and the absorbance values remained constant for 48h. Beer's law was obeyed with a good correlation coefficient in the concentration ranges 1-100 μg mL(-1) for BCG, BTB complexes and 1-95 μg mL(-1) for BPB complex. The composition ratio of the ion-pair complexes were found to be 1:1 in all cases as established by Job's method. No interference was observed from common additives and excipients which may be present in the pharmaceutical preparations. The proposed method was successfully applied for the determination of PX in capsule and human blood serum samples with good accuracy and precision.

  4. Synthesis and thermal characterization of new ternary chelates of piroxicam and tenoxicam with glycine and DL-phenylalanine and some transition metals

    Science.gov (United States)

    Zayed, M. A.; El-Dien, F. A. Nour; Mohamed, Gehad G.; El-Gamel, Nadia E. A.

    2006-05-01

    The ternary chelates of piroxicam (Pir) and tenoxicam (Ten) with Fe(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) in the presence of various amino acids such as glycine (Gly) or DL-phenylalanine (PhA) were prepared and characterized with different physicochemical methods. IR spectra confirm that Pir and Ten behave as a neutral bidentate ligand coordinated to the metal ions via the pyridine- N and carbonyl group of the amide moiety. Gly molecule acted as a uninegatively monodentate ligand and coordinate to the metal ions through its deprotonated carboxylic group. In addition, PhA acted as a uninegatively bidentate ligand and coordinate to the metal ions through its deprotonated carboxylic and amino groups. The solid reflectance spectra and magnetic moment measurements confirm that all the chelates have octahedral geometrical structures while Cu(II)- and Zn(II)-ternary chelates with PhA have square planar geometrical structures. Thermal behaviour of the complexes is extensively studied using TG and DTA techniques. TG results show that water molecules (hydrated and coordinated) and anions are removed in the first and second steps while Gly, PhA, Pir and Ten are decomposed in the next and subsequent steps. The pyrolyses of the chelates into different gases are observed in the DTA curves as exo- or endothermic peaks. Also, phase transition states are observed in some chelates. Different thermodynamic parameters are calculated using Coats-Redfern method and the results are interpreted.

  5. Effects of low-dose cyclophosphamide with piroxicam on tumour neovascularization in a canine oral malignant melanoma-xenografted mouse model.

    Science.gov (United States)

    Choisunirachon, N; Jaroensong, T; Yoshida, K; Saeki, K; Mochizuki, M; Nishimura, R; Sasaki, N; Nakagawa, T

    2015-12-01

    Low-dose cyclophosphamide (CyLD) has shown promise in the treatment of several cancers; however, the effect of CyLD on canine oral malignant melanoma has never been explored. In this study, we investigated the effects of CyLD with or without piroxicam (Px) on tumour neovascularization and vascular normalization in a canine oral malignant melanoma-xenografted mice model. After treatment with CyLD, Px or a combination of both (CyPx), the growth of the tumour in the treatment groups was significantly suppressed compared to the control group at 30 days of treatment. Proliferation index was also significantly reduced by all treatments, only CyPx significantly lowered microvessel density and vascular endothelial growth factor (VEGF) levels. Additionally, CyLD significantly reduced the proportion of normal vessels and caused an imbalance between VEGF and thrombospondin-1. These results suggested that CyPx has potent anti-angiogenic effects in terms of both the number and quality of blood vessels in xenografted canine oral malignant melanoma.

  6. Sensitive and selective spectrophotometric assay of piroxicam in pure form, capsule and human blood serum samples via ion-pair complex formation

    Science.gov (United States)

    Alizadeh, Nina; Keyhanian, Fereshteh

    2014-09-01

    A simple, accurate and highly sensitive spectrophotometric method has been developed for the rapid determination of piroxicam (PX) in pure and pharmaceutical formulations. The proposed method involves formation of stable yellow colored ion-pair complexes of the amino derivative (basic nitrogen) of PX with three sulphonphthalein acid dyes namely; bromocresol green (BCG), bromothymol blue (BTB), bromophenol blue (BPB) in acidic medium. The colored species exhibited absorption maxima at 438, 429 and 432 nm with molar absorptivity values of 9.400 × 103, 1.218 × 103 and 1.02 × 104 L mol-1 cm-1 for PX-BCG, PX-BTB and PX-BPB complexes, respectively. The effect of optimum conditions via acidity, reagent concentration, time and solvent were studied. The reactions were extremely rapid at room temperature and the absorbance values remained constant for 48 h. Beer’s law was obeyed with a good correlation coefficient in the concentration ranges 1-100 μg mL-1 for BCG, BTB complexes and 1-95 μg mL-1 for BPB complex. The composition ratio of the ion-pair complexes were found to be 1:1 in all cases as established by Job’s method. No interference was observed from common additives and excipients which may be present in the pharmaceutical preparations. The proposed method was successfully applied for the determination of PX in capsule and human blood serum samples with good accuracy and precision.

  7. A Study on the HPLC Method for the Determination of Piroxicam Gel%吡罗昔康凝胶有效成分的高效液相色谱研究

    Institute of Scientific and Technical Information of China (English)

    陈浩; 糜志远; 刘万忠

    2000-01-01

    本文提出了采用内标法,将HPLC用于吡罗昔康凝胶有效成分测定的新方法。讨论了流动相及内标的选择,进样量和空白基质的影响等。在优化的实验条件下,吡罗昔康浓度在0.02~0.2 mg/mL范围内,其浓度与吡罗昔康和内标的峰面积之比呈线性关系。应用于实际样品分析,其结果与紫外分光光度法一致,平均回收率为 99.6%,相对标准偏差为1.0%。方法简单,准确度高,专属性强,可用于吡罗昔康凝胶样品的稳定性考察和质量控制。%In this paper, a new method for the determination of Piroxicam gel by the use of HPLC was reported. The main factors, including the selection of mobile phase and internal reference materials and effects of inject ion volume and matrix were investigated. Under optimum chromatographic condition s, the calibration graph was linear in the range of 0.02-0.2 mg/mL, the average recovery was 99.6% with a relative standard deviation of 1.0%. The method has be en applied to the determination of Piroxicam gel, and their results were in good agreement with those obtained by UV method. The proposed method was simple, acc urate, specific and applicable to the analysis of Piroxicam gel and quality cont rol.

  8. Liquid chromatographic method for the simultaneous determination of captopril, piroxicam, and amlodipine in bulk drug, pharmaceutical formulation, and human serum by programming the detector.

    Science.gov (United States)

    Sultana, Najma; Arayne, M Saeed; Ali, Saeeda Nadir

    2013-10-01

    A highly sensitive LC method with UV detection has been developed for the simultaneous determination of coadministered drugs captopril, piroxicam, and amlodipine in bulk drug, pharmaceutical formulations, and human serum at the isosbestic point (235 nm) and at individual λmax (220, 255, and 238 nm, respectively) by programming the detector with time to match the individual analyte's chromophore, which enhanced the sensitivity with linear range. The assay involved an isocratic elution of analytes on a Bondapak C18 (10 μm, 25 × 0.46 cm) column at ambient temperature using a mobile phase of methanol/water 80:20 at pH 2.9 and a flow rate of 1.0 mL/min. Linearity was found to be 0.25-25, 0.10-6.0, and 0.20-13.0 μg/mL with correlation coefficient >0.998 and detection limits of 7.39, 3.90, and 9.38 ng/mL, respectively, whereas calibration curves for wavelength-programmed analysis were 0.10-6.0, 0.04-2.56, and 0.10-10.0 μg/mL with correlation coefficient >0.998 and detection limits of 5.79, 2.68, and 3.87 ng/mL, respectively. All the validated parameters were in the acceptable range. The recovery of drugs was 99.32-100.39 and 98.65-101.96% in pharmaceutical formulation and human serum, respectively, at the isosbestic point and at individual λmax . This method is applicable for the analysis of drugs in bulk drug, tablets, serum, and in clinical samples without interference of excipients or endogenous serum components.

  9. 吡罗昔康口崩片处方和工艺研究%Formulation and Preparation Technology of Piroxicam Orally Disintegrating Tablets

    Institute of Scientific and Technical Information of China (English)

    徐知; 彭红; 陈文杰

    2011-01-01

    制备了吡罗昔康口腔崩解片,并评价其质量.采用直接粉末压片法制备口腔崩片解,以片剂可压性、崩解时限、口感为指标.在先进行预试验的基础上,进行了最佳处方的筛选,并对其溶出度进行检测.结果采用最佳处方及制备工艺的吡罗昔康口崩片口感良好,与市售普通片比较,口腔崩解片具有明显速释效果.说明吡罗昔康口腔崩处方设计合理、制备工艺可行、产品质量可控.%To make Piroxicam orally disintegrating tablets and investigate its quality, the tablets were pre-pared using the direct compression method. The formulation was optimized with compressibility, disintegration time and taste as reference parameters, earlier on the basis of pre-test, the best prescription was screened and their dis-solutionwere examined. It is resulted the orally disintegrating tablets with the best formulation and preparation taste good, the orally disintegrating tablets had better fast release effect than marketed tablets. It is conclused that formu-lation design is reasonable, the process of preparation is feasible and the quality can be controlled.

  10. NS-398和Piroxicam抑制兔角膜新生血管的研究%Inhibition of NS-398 and Piroxicam on corneal neovascularization

    Institute of Scientific and Technical Information of China (English)

    李少华; 张黎; 肖青; 胡燕华

    2007-01-01

    目的 比较Piroxicam和NS-398对兔角膜新生血管(CNV)的抑制作用及两者对角膜上皮细胞的毒性作用.方法 将含20 μg大肠杆菌内毒素的缓释小丸植入兔角膜基质以诱导CNV.分别用浓度为0.1、1、10、100 μmol/L的Piroxicam和NS-398滴眼液滴眼,植入10 d后分析CNV的面积.MTT法分析二者对培养的角膜上皮细胞的毒性作用.结果 0.1 μmol/L NS-398和0.1 μmol/L Piroxicam组CNV生长浓密,两组其他浓度的CNV面积均有不同程度的减低.MTT法检测显示在0.5、5、50 μmol/L时,NS-398较Piroxicam对角膜上皮细胞的毒性低.结论 环氧化酶-1(COX-1)和COX-2特异性抑制剂对CNV形成均有抑制作用;相同浓度时,NS-398的抑制效果强于Piroxicam;在高浓度时NS-398较Piroxicam对角膜上皮细胞的毒性低.

  11. Desarrollo y optimización de una jalea de piroxicam 0,5 % Development and optimization related to a 0.5 % Piroxican jelly

    Directory of Open Access Journals (Sweden)

    Oscar García Pulpeiro

    2009-12-01

    Full Text Available Se desarrolló por primera vez en Cuba, una formulación de jalea de piroxicam al 0,5 %. Se tomó como referencia la composición de la formulación líder del mercado FELDENE GELâ, a la cual se le efectuaron algunas modificaciones. Se realizaron 4 experimentos en las evaluaciones preliminares que sirvieron de base para la etapa posterior de diseño y optimización de la formulación. Se aplicó un diseño de experimentos con mezcla, para lo cual se emplearon como variables independientes la concentración de Carbopol 940, trietanolamina y hidroxipropilmetilcelulosa. Se evaluó la influencia de estos componentes en el pH, el área de extensibilidad y en algunas propiedades organolépticas. A partir de estos resultados, se seleccionó una formulación óptima.For the first time in Cuba a 0.5 % Piroxican jelly formula was developed. The point of reference was the leader formula from FELEDENE GELâ; market which underwent some modifications. During first assessments four experiments were carried out as basis for the later stage of formula design and optimization. An experimental design with mixture was applied using as independent variables the concentration of Carbopol 940, Trietanolamine, and Hidroxypropyl methylcellulose. Influence of these components on pH, the extensibility area, and on some organoleptic properties. From these results, an optimal formula was selected.

  12. Piroxicam and c-phycocyanin prevent colon carcinogenesis by inhibition of membrane fluidity and canonical Wnt/β-catenin signaling while up-regulating ligand dependent transcription factor PPARγ.

    Science.gov (United States)

    Saini, Manpreet Kaur; Sanyal, Sankar Nath

    2014-06-01

    The colon cancer tissues from DMH treated rats exhibited higher membrane potential, fluidity and changed lipid order as examined by Merocyanine 540 and 1,6-diphenyl-1,3,5-hexatriene, respectively. A transition from gel to liquid crystalline state was observed by Laurdan fluorescence and also reduced fluorescence quenching of NBD-PE as contributed in the decreased membrane lipid phase separation. With piroxicam, a traditional NSAID and c-phycocyanin, a biliprotein from Spirulina platensis, these effects were normalized. An augmented intracellular Ca(+2) had contributed to the drug mediated apoptosis which is supported by an elevated calpain-9 expression. Histopathologically, a large pool of secreted acid/neutral mucopolysaccrides as well as the presence of blood vessels and dysplastic crypts signifies invasive mucinous adenocarcinoma while both the drugs reduced these neoplastic alterations. Wnt/β-catenin pathway was also found to be up-regulated which served as a crucial indicator for cancer cell growth. A concomitant down regulation of PPARγ was noted in DMH treatment which is associated with tumor progression. The expression of PPARα and δ, the other two isoforms of PPAR family was also modulated. We conclude that piroxicam and c-phycocyanin exert their anti-neoplastic effects via regulating membrane properties, raising calpain-9 and PPARγ expression while suppressing Wnt/β-catenin signaling in experimental colon carcinogenesis.

  13. Pharmacokinetics and Local Tissue Disposition of Piroxicam Following Topical and Oral Application in Rats%吡罗昔康口服和局部给药后药物动力学和局部组织的分布

    Institute of Scientific and Technical Information of China (English)

    李英剑; 潘妍; 徐晖; 魏刚; 郝劲松; 郑俊民

    2002-01-01

    目的研究大鼠吡罗昔康局部给药的药物传递和机理.方法大鼠分别局部给药和口服4mg吡罗昔康后,用HPLC法测定局部给药部位的皮肤、肌肉、关节和血液的药物浓度.结果口服给药后,Tjoint/Plasms和Tmus/Plasma比值保持恒定,大部分的时间其值介于0.06和0.2.比较而言,局部给药后,Tjoing/Plasma和Tmus/Plasma比值分别介于0.2到1.26和1.89到5.4之间.比值远远大于口服给药.结论数据表明局部给药后,到达局部深层组织的吡罗昔康来自于药物的直接渗透;当药物的靶向部位在局部时局部给药优于口服给药.%Objective To investigate the drug delivery and mechanism of topical administration of piroxicam in rats .Methods Four milligrams of piroxicam were administered to Wistar rats by either oral or topical routes. The drug concentrations in plasma, local tissues were determined by HPLC. Results After oral application, the Tjoint/Plasma and Tmulcle/Plasma ratios kept unchanged. During most of the experimental time(0- 24 h), the values varied between 0.06 and 0.2. In contrast,the Tjoing/Plasma and Tmuscle/Plasma ratios after local application varied from 0.2 to 1.26 and from 1.89 to 5.4 respectively and were much higher than the ones by oral application. Conclusion The results showed that most piroxicam reaching the local deep tissues was attributed to the direct penetration and topical delivery is superior to oral application when the drug's target is local tissues under skin.

  14. A high sensitive biosensor based on FePt/CNTs nanocomposite/N-(4-hydroxyphenyl)-3,5-dinitrobenzamide modified carbon paste electrode for simultaneous determination of glutathione and piroxicam.

    Science.gov (United States)

    Karimi-Maleh, Hassan; Tahernejad-Javazmi, Fahimeh; Ensafi, Ali A; Moradi, Reza; Mallakpour, Shadpour; Beitollahi, Hadi

    2014-10-15

    This study describes the development, electrochemical characterization and utilization of novel modified N-(4-hydroxyphenyl)-3,5-dinitrobenzamide-FePt/CNTs carbon paste electrode for the electrocatalytic determination of glutathione (GSH) in the presence of piroxicam (PXM) for the first time. The synthesized nanocomposite was characterized with different methods such as TEM and XRD. The modified electrode exhibited a potent and persistent electron mediating behavior followed by well-separated oxidation peaks of GSH and PXM. The peak currents were linearly dependent on GSH and PXM concentrations in the range of 0.004-340 and 0.5-550 µmol L(-1), with detection limits of 1.0 nmol L(-1) and 0.1 µmolL(-1), respectively. The modified electrode was successfully used for the determination of the analytes in real samples with satisfactory results.

  15. Inclusion Properties of Piroxicam by β-Cyclodextrin and Its Derivatives%β-环糊精衍生物与吡罗昔康的包合特性

    Institute of Scientific and Technical Information of China (English)

    王茹林; 王恩成; 秦姝竹; 王鹏

    2012-01-01

    采用荧光光谱、差热扫描和核磁共振法,研究了不同酸度下吡罗昔康(PX)与β-环糊精(β-CD)、羟丙基-β-环糊精(HP-β-CD)和磺丁醚-β-环糊精(SBE-β-CD)的包合特性.结果表明,吡罗昔康与3种环糊精均形成了1∶2.5的包合物.以包合常数为包合能力的量度,中性条件下,包合平衡常数分别为1.2×106、1.8 ×106、2.0×106,3种环糊精的包合能力为SBE-β-CD> HP-β-CD >β-CD.%The inclusion properties of piroxicam ( PX ) by β-cyclodextrin (β-CD ), hydroxypropyl-β- cyclodextrin ( HP-β-CD), and sulfobutyl ether-β-cyclodextrin ( SBE-β-CD) were studied by fluorescence spectroscopy, differential scanning calorimetry(DSC) and NMR at different pH. The results showed that the 1:2. 5 inclusion compounds were formed between piroxicam and CDs. Based on the formation constants, which were 2. 0× 106, 1. 8 × 106, 1. 2 × 106 in neutral media, the inclusion capacity showed the order of SBE-β- CD>HP-Β-CD>Β-CD.

  16. Efficacy of a Film-Forming Medical Device Containing Piroxicam and Sun Filters in the Treatment of Multiple Actinic Keratosis Lesions in a Subject with a History of Kaposi Sarcoma

    Science.gov (United States)

    Scotti, Elisabetta; Deledda, Salvatore; Milani, Massimo

    2016-01-01

    Actinic keratosis (AK) is considered a premalignant form of skin cancer due to chronic sun exposure. In addition, human papilloma virus (HPV) has been advocated a role in the pathogenesis of this clinical condition. HPV proteins (mainly E6 and E7) seem to act synergistically with ultraviolet (UV) radiation in reducing the defensive mechanisms of keratinocyte apoptosis after UV damage. Data regarding the involvement of other viruses, i.e. human herpes viruses (HHV), in the pathogenesis of AK are so far controversial. HHV8 is considered the infective agent involved in the development of Kaposi sarcoma. Some experimental data have shown that AK lesions carry HHV8 in more than 30% of the bioptic samples. Topical piroxicam was shown to be effective in the treatment of AK. In addition, the molecule shows antiviral action against HPV and HHV8. Here, we report the efficacy of a medical device containing a film-forming substance (polyvinyl alcohol), chemical and physical sun filters (SPF 50+), and 0.8% piroxicam (Actixicam™, Difa Cooper; ACTX) in the treatment of multiple scalp AK lesions, unresponsive to other treatments, in a subject with Kaposi sarcoma and a history of severe contact dermatitis. The subject presented with severe involvement of the scalp, with multiple hypertrophic AK lesions. Previous lesion-directed and field-targeted treatments have not been effective. The subject was treated with ACTX applied twice daily on the affected scalp. Relevant clinical improvement was observed as soon as 1 month of therapy. Complete clinical resolution of all scalp lesions was observed after 3 months of treatment. The product was well tolerated. PMID:28101017

  17. pH值对吡罗昔康理化性质及其经皮渗透性能的影响%Influence of pH on physico-chemical property and penetrable performance of piroxicam through rat skin

    Institute of Scientific and Technical Information of China (English)

    于秋菊; 刘丽清; 谢茵; 石恩娴; 任国莲; 田青平

    2012-01-01

    Objective: To determine the influence of pH on physico-chemical property of piroxicam and its percutaneous permeability. Methods; HPLC method was used to detect the solubility of piroxicam in water, and in various pH buffer solutions. Ambi-wavelength absorption spectrometry was used to determine the dissociation constant (pXa) of piroxicam. Shake-flask was used to determine the oil-water partition coefficient (logP) of piroxicam. The in vitro penetrable performance of piroxicam was evaluated by stable state permeation rate ( /s) and permeability coefficient (Ps). Results; The pKa of piroxicam was 6. 33. At 32 V, , logP of piroxicam in the buffer of pH 7.4 was 0. 17, in which its solubility and /, were the maximal, (420.445) ^g-mL"1 and (64.612 ±0.011) (ig-cm"2 'h~', respectively, compared with other pH values. The Pt of piroxicam in buffer of pH 7.4 was (0. 154 ± 0. 014) cm-h" . Conclusion; The adjusted pH can maintain a higher solubility and ratio of undissociated molecule of drug, which may be a promising means for improving percutaneous permeability of drug.%目的:研究pH值对吡罗昔康理化性质及经皮渗透性能的影响,为其经皮给药制剂的研究提供实验依据.方法:用HPLC法测定药物在水、不同pH缓冲液(PBS)中的溶解度;采用双波长分光光度法测定药物的解离常数(pKa);摇瓶法测定药物的表观油水分配系数(logP);利用透皮扩散池以稳态渗透速率常数(Js)和通透系数(Ps)为评价指标研究药物的透皮效果.结果:吡罗昔康的pKa为6.33.32℃时,吡罗昔康在pH 7.4的缓冲液中logP为0.17,且溶解度和Js均达到最大,分别为(420.445) μg· mL -1和(64.612±0.011) μg·cm-2·h-1;Ps为(0.154士0.014)cm·h-1.结论:调节药物pH值,使药物维持较高的溶解度和分子型药物比例,可望获得理想的皮肤通透性.

  18. Piroxicam与NS-398对角膜新生血管抑制作用及对兔角膜上皮毒性作用的比较%NS-398 inhibits corneal neovascularization with lower cytotoxicity on corneal epithelial cell than Piroxicam in rabbits

    Institute of Scientific and Technical Information of China (English)

    李少华; 张黎; 肖青; 胡燕华

    2004-01-01

    目的:比较Piroxicam(环氧化酶-1选择抑制剂)和NS-398(环氧化酶-2选择性抑制剂)对角膜新生血管的抑制作用并比较两者对角膜上皮细胞的毒性作用.方法:将含20u g脂多糖的缓释小丸植入兔角膜基质以诱导角膜新生血管.使用不同浓度的Piroxicam和NS-398滴眼剂滴眼,植入10d后分析角膜新生血管的面积.采用MTT法分析Piroxicam和NS-398对角膜上皮细胞的毒性作用.结果:0.01 u mol/L NS-398和口0.01 u mol/L Piroxicam组兔角膜新生血管生长浓密,其它组因抑制剂的不同及浓度的不同角膜新生血管面积有不同程度的减低.在0.5,5及50μmol/L时,NS-398较Piroxicam对角膜上皮细胞的毒性低.结论:环氧化酶-1特异性抑制剂和环氧化酶-2特异性抑制剂对角膜新生血管形成均有抑制作用.相同浓度时,NS-398的抑制效果强于Piroxicam.在高浓度时NS-398较Piroxicam对角膜上皮细胞的毒性低.%AIM: To compare the inhibitive effect of Piroxicam (cyclooxygenase-1 selective inhibitor, COX-1 inhibitor) and NS-398 (cyclooxygenase-2 selective inhibitor, COX-2 inhibitor) on corneal neovascularization and their cytotoxity on corneal epithelial cells in vitro.METHODS: Slow-release pellets containing lipopolysac charide 20 μ g were prepared and implanted into the rabbit' s corneal stroma near the limbus to induce neovascularization. Eye drops containing NS-398 or Piroxicam at various concentrations were applied. Ten days after the implantation of pellet, the neovascularization was examined and cytotoxicity of the two materials on comeal epithelium cells was analyzed by MTT assay.RESULTS: In the 0.01 μ mol/L Piroxicam group, therewas dense neovascularization. In the other groups, neovascularization decreased to different degrees, depending on the drug and concentration applied. The cytotoxicity of NS-398 was lower than that of Piroxicam at 0.5, 5 and 50 μ mol/L and the difference had statistical significance.CONCLUSION: Both

  19. Diseño y validación de un método espectrofotométrico para el control de calidad del piroxicam jalea 0,5 %

    Directory of Open Access Journals (Sweden)

    Yania Suárez Pérez

    Full Text Available La jalea de piroxicam al 0,5 % es un nuevo producto en fase de desarrollo de la Empresa Laboratorio "Roberto Escudero Díaz". En el presente trabajo se diseñó un método por espectrofotometría UV, para lo cual se empleó ácido clorhídrico etanólico como disolvente y 328 nm como longitud de onda de máxima absorción. Se estableció un procedimiento simple y rápido para procesar la muestra previa al análisis. Posteriormente se aplicó la validación de este según exigencias regulatorias actuales. El método resultó suficientemente específico, lineal, preciso y exacto en el rango de 3,125 a 9,375 µg/mL. Se aplicó a la cuantificación del principio activo en 3 lotes de la formulación desarrollada, con resultados satisfactorios sin diferencias estadísticamente significativas según el procesamiento aplicado.

  20. Pharmacokinetics of piroxicam-β-cyclodextrin inclusion complexes in Beagle dogs%吡罗昔康环糊精包合物在Beagle犬体内的药物动力学研究

    Institute of Scientific and Technical Information of China (English)

    张建明; 吴江; 方晓玲

    2012-01-01

    目的 研究吡罗昔康环糊精包合物Beagle犬体内药物动力学.方法 6只Beagle犬采用随机、双周期交叉给药,单剂量灌胃给予吡罗昔康受试制剂或参比制剂,用HPLC法测定吡罗昔康血浆浓度,用统计矩原理进行血药浓度-时间数据分析.结果 吡罗昔康包合物的达峰时间tmax快于普通片剂,分别为(0.89 ±0.09)、(3.92±0.49)h,两者有显著差异(P<0.01),两者的半衰期t1/2分别为(31.30±4.38)、(29.38±1.83)h,曲线下面积(AUC0~1)分别为(242.92±30.04)、(230.55±8.06)μg(h·ml),最高血药浓度(Cmax)分别为(7.82±0.44)、(7.49±0.36)μg/ml,清除率(Cl)分别为(80.92±10.65)、(85.27±2.95)ml/h,表观分部容积(Vd)分别为(3.36±0.51)、(3.22±0.19)L,均无明显差异(P>0.05),吡罗昔康包合物相对于市售片剂的相对生物利用度为106.74%.结论 建立的HPLC分析方法准确可靠.两种剂型的生物利用度相似,将吡罗昔康制成包合物后能大大加快药物在体内的吸收速度,使其更快发挥药效.%Objective To study the pharmacokinetics of piroxicam-|3-cyclodextrin inclusion complexes in Beagle dogs. Methods An open randomized two-period crossover self-control trial was conducted in 6 Beagle dogs. Piroxicam in the plasma was assayed by HPLC after a single oral dose of 20 mg piroxicam in test complexes (capsules) and reference tablets. The serum concentration-time data were analyzed by non-compartment-al model. Results The tmaxof the capsules and the tablets were 0. 89 ±0.09 and 3.92 ±0.49 h, respectively, with the former significantly shorter than the latter. The t1/2 were 31.30 ±4.38 and 29.38 ± 1.83 h, respectively. The AUC were 242.92 ±30.04 and 230.55 ±8.06 g/(h ? ml). The Cmaxwere 7.82 ±0.44 and 7.49 ±0.36 g/ml. The Cl were 80.92 ± 10.65 and 85.27 ±2.95 ml/h. The Vd were 3.36 ±0.51 and 3.22 ±0.19 L, respectively. These above indexes had no significant difference between 2 groups. The relative bioavailability of

  1. Study the Anti-inflammatory and Analgesic Effects of Piroxicam Microemulsions on Mice%吡罗昔康新制剂微乳的药效学研究

    Institute of Scientific and Technical Information of China (English)

    刘娜; 杨保仲; 王颖莉; 葛曙光

    2013-01-01

    Objective:To prepare piroxicam miroemulsion and study its anti-inflammatory and analgesic effects,observe the continuous medication on skin morphology,and compare with piroxiam gel. Method:The microemulsion was prepared with the system contained of Lauroglycol FCC as oil phase,Labrasol and Cremophor EL as surfactants,Transcutol P as consurfactants,piroxicam,water 1%dichlofenac sodium gel was used as positive control,xylene and carrageenan were used to induce ear edema in mice and pedal swelling in rats respectively in order to study anti-inflammatory effect of Piroxiam microemulsion. The hot-plate test and writhing test was adopted to study the analgesic effect,then compared with Piroxiam gel. Result:Middle dose and high dose Piroxiam miroemulsion was equal or superior to positive control in anti-inflammatory and analgesic effect. Compared with piroxiam gel, it had longer action time and more stable effects. In addition,there was no irritation to the skin. Conclusion:Piroxiam miroemulsion has significant anti-inflammatory and analgesic effects,it is expected to become a new formulation.%  目的:制备吡罗昔康微乳新剂型,对其抗炎、镇痛作用进行初步药效学研究,观察连续用药对皮肤组织形态学的改变,并与凝胶制剂进行比较。方法:采用油相Lauroglycol FCC,表面活性剂Labrasol、Cremophor EL,助表面活性剂Transcutol P、吡罗昔康及水制备吡罗昔康微乳,1%的双氯芬酸钠凝胶剂作为阳性对照药,采用二甲苯诱导小鼠耳廓肿胀,卡拉胶诱发大鼠足跖肿胀,痛阈提高率和醋酸致小鼠扭体实验,对吡罗昔康微乳的抗炎镇痛作用进行初步探讨并与市售的吡罗昔康凝胶进行比较。结果:吡罗昔康微乳具有抗炎镇痛作用,中、低剂量的吡罗昔康微乳与阳性对照组比较均显示相近或更强的抗炎镇痛作用,与吡罗昔康凝胶组比较,作用强、时间长、效果平稳,且对皮肤无刺激性。结论:吡罗昔康

  2. 环氧合酶-2抑制剂吡罗昔康对结肠癌细胞生长的影响%Effects of cyclooxygenase-2 inhibitor Piroxicam on the growth of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    于成功; 陈慧; 徐肇敏

    2004-01-01

    目的观察非甾体类抗炎药、环氧合酶(COX)-2抑制剂吡罗昔康(Piroxicam)对结肠癌细胞的影响,并结合COX-2蛋白表达和细胞凋亡情况探讨结肠癌的预防.方法细胞株选用SW 1116结肠腺癌细胞;细胞增殖实验时,用MTT法测定细胞增殖活性;用免疫组化及Western Blot方法检测细胞内COX-2蛋白表达;用DNA云梯电泳法检测细胞凋亡.结果吡罗昔康能够抑制结肠腺癌细胞的增殖,其效应与浓度呈正相关;浓度≥1.0 mmol/L时呈现细胞毒作用.吡罗昔康作用12 h即可显著抑制COX-2蛋白的表达;作用24 h后,蛋白水平恢复程度与浓度成负相关.吡罗昔康浓度≥0.1 mmol/L时可以诱导SW 1116细胞的凋亡.结论吡罗昔康抑制结肠腺癌细胞的增殖与抑制COX-2过度表达和促进细胞凋亡有关,由于吡罗昔康的效应呈现浓度和时间依赖性,在进行预防或治疗结肠癌的临床研究时,要考虑其有效剂量和用药间隔.

  3. Synthesis, investigation and spectroscopic characterization of piroxicam ternary complexes of Fe(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) with glycine and DL-phenylalanine

    Science.gov (United States)

    Mohamed, Gehad G.; El-Gamel, Nadia E. A.

    2004-11-01

    The ternary piroxicam (Pir; 4-hydroxy-2-methyl- N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) complexes of Fe(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) with various amino acids (AA) such as glycine (Gly) or DL-phenylalanine (PhA) were prepared and characterized by elemental analyses, molar conductance, IR, UV-Vis, magnetic moment, diffuse reflectance and X-ray powder diffraction. The UV-Vis spectra of Pir and the effect of metal chelation on the different interligand transitions are discussed in detailed manner. IR and UV-Vis spectra confirm that Pir behaves as a neutral bidentate ligand coordinated to the metal ions via the pyridine- N and carbonyl group of the amide moiety. Gly molecule acted as a uninegatively monodentate ligand and coordinate to the metal ions through its carboxylic group, in addition PhA acted as a uninegatively bidentate ligand and coordinate to the metal ions through its carboxylic and amino groups. All the chelates have octahedral geometrical structures while Cu(II)- and Zn(II)-ternary chelates with PhA have square planar geometrical structures. The molar conductance data reveal that most of these chelates are non electrolytes, while Fe(III)-Pir-Gly, Co(II)-, Ni(II)-, Cu(II)- and Zn(II)-Pir-PhA cheletes were 1:1 electrolytes. X-ray powder diffraction is used as a new tool to estimate the crystallinity of chelates as well as to elucidate their geometrical structures.

  4. 吡罗昔康-Cu(Ⅱ)-牛血清白蛋白相互作用的荧光光谱法研究%Fluorescence Spectrum Characteristics of Complex of Piroxicam,Copper ( Ⅱ ) and BSA

    Institute of Scientific and Technical Information of China (English)

    阿娟; 赵智宏; 安娜; 刘慧民

    2011-01-01

    The effects of Piroxicam(PIR),Cu ( Ⅱ ) on the fluorescence spectrum characteristics of bovine serum albumin(BSA)were studied. The effect of Cu ( Ⅱ ) on the fluorescence spectrum characteristics of PIR-BSA complex was also investigated. The results showed that both Cu ( II ) and PIR could quench the fluorescence intensity of BSA via a nonradiative energy transfer mechanism. Moreover,when Cu ( Ⅱ ) was present PIR could more significantly quench the fluorescence of BSA. The binding constants (it) and the binding sites (n) were calculated after analyzing fluorescence quenching data with a double - reciprocal equation. K and n between PIR and BSA were 3.18×10 3L/mol and 0. 75 respectively in the PIR-BSA complex, while that between Cu ( Ⅱ) and BSA were 1.13 ×103 L/mol and 0. 74 respectively in the binary complex of copper ( Ⅱ) and BSA.%应用荧光光谱法研究了生理条件下吡罗昔康对牛血清白蛋白,Cu(Ⅱ)对牛血清白蛋白以及Cu(Ⅱ)对吡罗昔康和牛血清白蛋白荧光光谱特性的影响.结果表明:Cu(Ⅱ)和吡罗昔康均可使牛血清白蛋白的荧光强度发生静态猝灭,并且在Cu(Ⅱ)存在下,吡罗昔康对牛血清白蛋白的荧光猝灭作用显著增强.根据荧光猝灭双倒数图计算吡罗昔康和牛血清白蛋白的结合常数为3.18×103L/mol,结合位点数为0.75;二元配合物Cu(Ⅱ)与牛血清白蛋白之间的结合常数为1.13×103 L/mol,结合位点数为0.74.

  5. Clinical Observation of Glucosamine Hydrochloride Combined Piroxicam Patch in the Treatment of 98 cases of Knee Osteoarthritis%盐酸氨基葡萄糖联合吡罗昔康贴片治疗膝骨关节炎98例疗效观察

    Institute of Scientific and Technical Information of China (English)

    张玉玲; 吕明

    2015-01-01

    目的 观察分析盐酸氨基葡萄糖胶囊(奥泰灵) 联合吡罗昔康贴片治疗膝骨关节炎的疗效. 方法 选取诊断为膝关节骨关节炎患者98例,随机分为治疗组和对照组,治疗组49 例用盐酸氨基葡萄糖胶囊联合吡罗昔康贴片治疗,对照组病例采用口服双氯芬酸钠胶囊治疗1 次25mg,1日3次,治疗组口服盐酸氨基葡萄糖胶囊0.75g,1日2次饭后,连续服用6周为1个疗程,治疗3个疗程,并且外用吡罗昔康贴片比较两种不同治疗方法的效果. 结果 两组患者在关节压痛、平地行走痛、静息痛、晨起关节僵硬、及行走能力上均有明显改善,治疗组明显优于对照组,统计学分析有显著性差异( P<0.05 ) ,临床治疗总有效率亦明显高于对照组. 两组治疗后1年半内复发病例比较P<0.05 ,与对照组比较具有统计学意义. 结论 盐酸氨基葡萄糖胶囊联合吡罗昔康贴片对治疗膝骨关节炎有明显作用,能有效地改善关节的功能,减轻临床症状,提高治愈率,远期疗效好,复发率低,值得推广.%OBJECTIVE To observe and analyze the treatment of knee osteoarthritis with Glucosamine hydro-chloridecapsuleandPiroxicamPatch.METHODS 98kneeosteoarthritispatientswererandomlydividedintotreat-ment group and control group .49 patients in treatment group were treated with Glucosamine hydrochloride capsule and Piroxicam Patch;other patients in control group were treated with Diclofenac Sodium Enteric-coated Tablets, 25 mg for each time , tid.Treatment group were treated with Glucosamine hydrochloride capsule ( 0.75 g ) , bid after meal,6 weeks as one treatment course ,consecutively 3 courses,and meanwhile,using Piroxicam Patch Compare the efficacy of these two different treatments .RESULTS obvious improvement in terms of joint pain ,walking pain ,rest pain,joint stiffness and walking ability for two groups of patients were observed ,while treatment group was much bet-ter than control group as shown with

  6. Electrochemical behavior of Piroxicam on a glassy carbon electrode modified with nano-Fe3 O4-reduced graphene oxide and its electrochemical determination%吡罗昔康在纳米Fe3 O4-石墨烯复合修饰玻碳电极上的电化学行为及电分析研究

    Institute of Scientific and Technical Information of China (English)

    张青春; 张志华; 张瑞; 彭娟; 高作宁

    2015-01-01

    The nano-Fe3 O4 and reduced graphene oxide ( RGO ) composite modified glassy carbon electrode ( nano-Fe3 O4-RGO/GCE)was fabricated,the electrochemical behavior and electrochemical properties of the anti-inflammatory drug Piroxicam(PC)at the nano-Fe3 O4-RGO/GCE,RGO/GCE and GCE were investigated by electrochemical impedance spectroscopy( EIS) ,cyclic volta-mmetry(CV),square wave voltammetry(SWV),chronoamperometry(CA)and chronocoulometry(CC). The experimental results showed that the electrochemical response of PC is much greater on the nano-Fe3 O4-RGO/GCE than on the bare glassy carbon elec-trode. the oxidation peak currents increased linearly range from 2. 0×10-6 to 2. 0×10-4 mol·L-1 with the detection limit(S/N=3)of 5. 3×10-7 mol·L-1 and the recoverage is in the range of 100. 0% ~104. 0%. Compared with other modified electrode,the nano-Fe3 O4-graphene modified glassy carbon electrode was convenient to prepare,and it exhibited a satisfactory accuracy and precision, and long-term stability,and could be used in the determination of piroxicam in pharmaceutical.%采用纳米Fe3 O4粒子( nano-Fe3 O4)和石墨烯( Reduced Graphene Oxide,RGO)制备了nano-Fe3 O4-RGO复合材料修饰玻碳电极(nano-Fe3O4-RGO/GCE),采用循环伏安法(cyclic voltammetry,CV),方波伏安法(square wave voltammetry,SWV),计时电流法( chronoamperometry,CA),计时库仑法( chronocoulometry,CC)研究了吡罗昔康( Piroxicam,PC)在此复合修饰电极上的电化学行为及电化学动力学性质。实验结果表明,与GCE相比, nano-Fe3 O4-RGO/GCE对PC的电化学氧化作用有显著的促进作用,其氧化峰电流显著增加;对各种实验条件进行了优化,测得峰电流Ipa与PC浓度在2.0×10-6~2.0×10-4 mol·L-1范围内呈良好的线性关系,检出限(S/N=3)为5.3×10-7 mol·L-1,加标回收率为100.0%~104.0%。该方法快速,灵敏,并将nano-Fe3O4-RGO/GCE用于市售吡罗昔康片剂的测定,结果符合定量测定要求。

  7. 顶空-气相色谱法测定吡罗昔康原料药中有机溶剂残留量%Determination of Residual Organic Solvents in Raw Medicinal Piroxicam by Head-Space Gas Chromatography

    Institute of Scientific and Technical Information of China (English)

    彭炳先

    2011-01-01

    Four residual organic solvents, including ethanol, acetone, chloroform and toluene, in raw medicinal piroxicam were determined by head-space GC. The temperature and time chosen for equilibration of the sample in the head space vessel were 65℃ and 30 min respectively. Capillary chromatographic column, Rtx-1 (0. 25 mm×30 m, 0. 25 μm) was used for the separation, and hydrogen FID was adopted in the determination. Under the optimum conditions, the 4 organic solvents were separated within 10 min, and the separation factor attained was more than 1. 5. Linear relationships between values of peak area and mass concentration of the 4 organic solvents were obtained in definite ranges, with detection limit (3S/N) in the range of 0. 043 0. 114 mg · L-1. The proposed method was applied to the analysis of raw medicinal piroxicam, both ethanol and acetone was detected. Values of recovery found by standard addition method were ranged from 98.1% to 101.7%.%提出了顶空-气相色谱法测定吡罗昔康原料药中残留的4种有机溶剂(乙醇、丙酮、氯仿和甲苯)的方法。分别选择65℃及30min作为样品在顶空瓶中的平衡温度和平衡时间。选用RtX-1毛细管色谱柱(0.25mm×30m,0.25μm)分离,氢火焰离子化检测器测定。4种有机溶剂在10min内能完全分离,分离度大于1.5。4种有机溶剂的质量浓度在一定的范围内与其峰面积呈线性关系,检出限(3S/N)在0.043-0.114mg·L-1之间。方法用于吡罗昔康原料药样品分析,仅检出残留溶剂乙醇和丙酮。加标回收率在98.1%~101.7%之间。

  8. Determination of Vitamin B1 Piroxicam and Prednisone Acetate in Compound Arthritis Capsules by HPLC%HPLC测定复方关节炎胶囊中维生素B1、吡罗昔康和醋酸泼尼松

    Institute of Scientific and Technical Information of China (English)

    冯维希; 陈坚; 陈乃江; 张源源

    2011-01-01

    Objective: To analyze western medicines added in Compound Arthritis Capsules by High performance liquid chromatography-diode array detector (HPLC-DAD).Method: To identify and determine of vitamin B1, piroxicam and prednisone acetate in compound arthritis capsules by HPLC-DAD.The HPLC conditions were as follows: column of Phenomenex luna ODS C18 (4.6 mm × 250 mm, 5 μm), mobile phase consisted of acetonitrile-0.1% phosphoric acid solution (62∶ 38), detection wavelength of 254 nm, flow rate of 1.0 mL· min-1 and column temperature of 30 ℃.Result: Compound arthritis capsules contained vitamin B1, piroxicam and prednisone acetate and the contents were 22.6, 13.8, 7.12 mg·g-1.Conclusion: The methods is simple, reliable and can used to analyze western medicines added in traditional Chinese medicines.%目的:建立了高效液相色谱-二极管阵列检测器(HPLC-DAD)测定复方关节炎胶囊中维生素B1、吡罗昔康和醋酸泼尼松3种西药成分.方法:采用HPLC-DAD分析技术确定复方关节炎胶囊中3种西药成分,并对其进行含量测定.色谱柱Phenomenex Luna ODS C(4.6 mm×250 mm,5μm),流动相为乙腈-0.1%磷酸溶液(38:62),柱温室温,流速1.0 mL·min-1,检测波长254 nm.结果:复方关节炎胶囊中检出维生素B1、吡罗昔康和醋酸泼尼松3种西药成分含量分别为22.6,13.8,7.12mg·g-1.结论:方法简便,结果准确,可作为中药制剂中西药成分的检测分析方法.

  9. Diseño y validación de un método espectrofotométrico para el control de calidad del piroxicam jalea 0,5 % Design and validation of a spectrophotometry method used in quality control of a 0,5 % Piroxican jelly

    Directory of Open Access Journals (Sweden)

    Yania Suárez Pérez

    2009-12-01

    Full Text Available La jalea de piroxicam al 0,5 % es un nuevo producto en fase de desarrollo de la Empresa Laboratorio "Roberto Escudero Díaz". En el presente trabajo se diseñó un método por espectrofotometría UV, para lo cual se empleó ácido clorhídrico etanólico como disolvente y 328 nm como longitud de onda de máxima absorción. Se estableció un procedimiento simple y rápido para procesar la muestra previa al análisis. Posteriormente se aplicó la validación de este según exigencias regulatorias actuales. El método resultó suficientemente específico, lineal, preciso y exacto en el rango de 3,125 a 9,375 µg/mL. Se aplicó a la cuantificación del principio activo en 3 lotes de la formulación desarrollada, con resultados satisfactorios sin diferencias estadísticamente significativas según el procesamiento aplicado.The 0.5 % jelly Piroxican is a new product in developing phase from "Roberto Escudero Díaz" Laboratory Enterprise. In present paper a UV spectrophotometry method was designed using ethanol chloride acid as solvent and 328 nm as maximal absorption wave length. A simple and fast procedure was established to processing the sample previous to analysis. Subsequently, we applied the validation of it according current regulatory demands. Method was enough specific, linear, precise and exact at the 3.125 to 9.375 µg/mL. Active principle quantification was applied in three batches of developed formula achieving satisfactory results without statistically significant differences according the applied procedure.

  10. Polarographic determination of piroxicam%吡洛昔康的极谱测定

    Institute of Scientific and Technical Information of China (English)

    马淮凌; 徐茂田; 宋俊峰

    2005-01-01

    在0.06 mol/L HAc-NaAc (pH 4.5±0.1)缓冲溶液中,吡洛昔康于-1.23 V (vs. SCE)处产生一灵敏的极谱催化氢波,其二阶导数峰电流与吡洛昔康浓度在2.0×10-8~5.6×10-6 mol/L范围内呈线性关系(r=0.9990, n=8),检出限为1.0×10-8 mol/L.该方法可用于药剂中吡洛昔康的测定.

  11. Dissolution of piroxicam tablets%吡罗昔康片溶出度考察

    Institute of Scientific and Technical Information of China (English)

    何琳

    2009-01-01

    目的 考察不同厂家吡罗昔康片在不同pH值溶出介质中的体外溶出情况.方法 采用中国药典溶出度第二法装置、转速50、75 r·min-1、溶出介质均为900 ml.uV法测定吡罗昔康溶出度.结果 在pH6.8磷酸盐缓冲液中各厂家吡罗昔康片的溶出在20 min达到70%以上,在pH1.2盐酸溶液中,基本达到(2005年版)的规定(既45 min溶出度分别≥70%);在pH4.5醋酸盐缓冲液60 min达到70%以上,在水中90 min时只达64%.结论 在四种溶出介质中溶出差异显著,在水中溶出达不到要求.不同厂家及同一厂家的不同批次溶出差异显著.

  12. 吡罗昔康工艺的改进%Improvement of Piroxicam Synthesis

    Institute of Scientific and Technical Information of China (English)

    付金广

    2013-01-01

    糖精钠与氯乙酸乙酯缩合得3-氧代-1,2-苯并异噻唑啉-2-乙酸甲酯-1,1二氧化物,甲醇钠作碱,经N-甲基化,得2-甲基-3,4-二氧-4-氧化-2H-1,2-苯并噻嗪-3-羧酸甲酯-1,1-二氧化物,再与2-氨基吡啶反应得吡罗昔康.重拍扩环采用一勺烩的合成方法,通过酸碱沉淀进行精致后,总收率达到72%.

  13. Mecanismos patogénicos de las lesiones gastrointestinales inducidas por meloxicam y piroxicam.

    OpenAIRE

    Villegas Lama, Isabel

    2001-01-01

    Falta Palabras clave Los antiinflamatorios no esteroides (AINE) se encuentran entre los fármacos más consumidos en todo el mundo. Su amplia utilización está avalada por sus propiedades analgésicas, antiinflamatorias y antipiréticas. Sin embargo, el uso de estos fármacos se acompaña de efectos secundarios, que pueden aparecer hasta en el 25% de los pacientes, siendo los relacionados con el tracto digestivo un número importante. Se ha descrito todo un abanico de reacciones adversas a este ni...

  14. Drug: D05511 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05511 Drug Piroxicam betadex (USAN) (C42H70O35)5. (C15H13N3O4S)2 6333.9742 6337.61...xicam D05511 Piroxicam betadex (USAN) M02 TOPICAL PRODUCTS FOR JOINT AND MUSCULAR...r topical use M02AA07 Piroxicam D05511 Piroxicam betadex (USAN) USP drug classification [BR:br08302] Analges...ics Nonsteroidal Anti-inflammatory Drugs Piroxicam D05511 Piroxicam betadex (USAN...) Anti-inflammatory Agents Nonsteroidal Anti-inflammatory Drugs Piroxicam D05511 Piroxicam betadex (USAN) Ta

  15. Study on Determination of Piroxicam in Piroxicam Capsules by RP-HPLC%反相高效液相色谱法测定吡罗昔康胶囊中吡罗昔康含量

    Institute of Scientific and Technical Information of China (English)

    李存金; 郭飞宇

    2010-01-01

    目的 建立测定吡罗昔康胶囊中吡罗昔康含量的反相高效液相色谱法.方法 色谱柱为Kromasil C18柱(250 mm×4.6 mm,5μm),流动相为磷酸二氢钾溶液(1.36 g磷酸二氢钾,加水750 mL,振摇使溶解,加1.7%浓磷酸溶液116 mL,加水至1 000 mL)-甲醇(45:55),流速1.0 mL/min,检测波长361 nm.结果 吡罗昔康对照品溶液质量浓度在19.712~118.272μg/mL范围内与峰面积线性关系良好,r=0.999 9,平均回收率为98.64%,RSD为0.42%(n=6).结论 所用方法快速、简便、准确、重现性好.

  16. [Endoscopic, histologic and morphometric evaluation of the gastric mucosa in patients with osteoarthritis treated with piroxicam and zinc acexamate].

    Science.gov (United States)

    Guilarte López-Mañas, J; Valenzuela Barranco, M; Caballero Plasencia, A M; Martín Ruiz, J L

    1998-05-01

    Zinc acexamate (ZAM) is an antiulcer agent with antisecretory and gastroprotective properties. The aim of this study was to evaluate endoscopically and morphometrically the efficacy of ZAM in the prophylaxis of gastroduodenal lesions induced by pyroxicam. Thirty nine patients from 30 to 70 years of age diagnosed with osteoarthritis without lesions in the upper digestive tract on basal endoscopy were studied. A randomized, double blind study was designed in which the patients received 20 mg/day of pyroxicam together with 300 mg/day of ZAM or placebo for 4 weeks. Clinical controls were undertaken on days 0, 14, 28 and endoscopic and histologic controls performed on days 0 and 28. The two groups were homogeneous regarding basal parameters. Endoscopic grading of the gastroduodenal lesions at the end of the study was lower in the group treated with ZAM (p < 0.001). Ulcers were found in only 2 patients (one antral and one duodenal) both of whom were in the placebo group (10.5%). Histologic scoring following treatment demonstrated higher values in the placebo group (p < 0.001) and scarce alterations with respect to base values in the group treated with ZAM. Morphometric quantification showed lower cell densities in both groups at the body level (p < 0.001). However, these did not vary in the antrum in the group treated with ZAM but increased in the placebo group (p < 0.001) as an expression of proliferative cell response to mucosal damage. At a single nightly dosis of 300 mg ZAM is effective in the prophylaxis of gastric and duodenal lesions induced by pyroxicam.

  17. Controlled-delivery patch of piroxicam%吡罗昔康透皮控释贴片

    Institute of Scientific and Technical Information of China (English)

    杨莉; 赵志刚

    2008-01-01

    吡罗昔康为一高效非甾体抗炎药(NSAIDs),但因不良反应限制了其口服剂型的应用;其透皮控释贴片直接作用于患处,在局部靶组织发挥疗效,安全方便、刺激小且可持续发挥药效48 h.现对吡罗昔康透皮控释贴片的药理作用、药动学、临床评价等进行综述.

  18. 美洛昔康和炎痛喜康的合成%Synthesis of Meloxicam and Piroxicam

    Institute of Scientific and Technical Information of China (English)

    吴范宏; 王葆丹; 奚关根

    2002-01-01

    以氯乙酸异丙酯和糖精钠为原料,经过4-羟基-2-甲基-2H-1,2-苯并噻嗪-3-羧酸异丙酯1,1-二氧化物中间体对美洛昔康和炎痛喜康进行合成研究.总收率分别为53.9%和51.9%.

  19. 流动注射化学发光抑制法测定吡罗昔康%Determination of Piroxicam by Flow Injection Quenching Chemiluminescence

    Institute of Scientific and Technical Information of China (English)

    王金中; 刘波; 周艳梅

    2005-01-01

    基于吖啶橙在氢氧化钠介质中能被高锰酸钾氧化产生较强的化学发光,吡罗昔康能强烈抑制其化学发光,建立了高锰酸钾-吖啶橙-吡罗昔康化学发光抑制测定吡罗昔康的新方法.吡罗昔康在1.0×10-5~7.0×10-4g/mL范围内与化学发光强度呈良好线性关系,方法的检出限为4.5×10-6g/mL,对1.0×10-5g/mL吡罗昔康连续进行6次测定的相对标准偏差为3.6%.

  20. Studies on the prescription and preparation of piroxicam tablets%吡罗昔康片处方工艺的改进研究

    Institute of Scientific and Technical Information of China (English)

    张瑛; 剌贵荣

    2003-01-01

    目的通过对吡罗昔康片处方及工艺的改进提高其溶出度.方法采用正交实验设计方法,以溶出度测定结果为指标进行处方筛选.结果筛选后的处方可达到中国药典2000年版对溶出度的要求.结论该片剂处方合理,制备工艺简单易行,适合工业化生产.

  1. Determination of Piroxicam in human plasma by HPLC%HPLC测定人血浆中吡罗昔康的浓度

    Institute of Scientific and Technical Information of China (English)

    李乐丹

    2009-01-01

    目的 建立测定人血浆中吡罗昔康含量的方法.方法 采用HPLC法,色谱柱为C_(18)柱(250 mm×4.6 mm,5μm),内标物为美洛昔康,流动相为0.2 mol·L~(-1)磷酸二氢钾缓冲液(磷酸调pH4)-甲醇(30:70),检测波长为360 nm,流速为1.0 mL·min~(-1),柱温为25℃.结果 20、100、400、800μg·L~(-1)吡罗昔康的平均回收率分别为92.61%、93.82%、95.11%、98.92%,日内、日间RSD分别为2.76%~4.22%、2.83%~4.05%,吡罗昔康0.02~1.00 mg·L~(-1)与峰面积呈良好的线性关系(r=0.9992),最低检测限为19.5μg·L~(-1)(S/N=3).结论 所用方法灵敏、准确、简单、快速,可用于临床血药浓度的监测和药动学的研究.

  2. Inclusion Interaction of Piroxicam and Sulfocalixarene[8]%吡罗昔康与磺化杯芳烃[8]的包合作用研究

    Institute of Scientific and Technical Information of China (English)

    吕俊杰; 王茹林; 李瑞翔; 刘文

    2013-01-01

    采用荧光光谱研究了不同酸度和温度下,吡罗昔康(PX)与磺化杯芳烃[8](SCX8)的包合作用,结果表明在酸性和中性条件下,吡罗昔康与磺化杯芳烃[8]均形成了1∶1的包合物.以包合形成常数为包合物稳定性的量度,中性>酸性,碱性条件下包合物不能形成.随着温度的增加杯芳烃的包合能力呈下降的趋势.

  3. 吡罗昔康-β-环糊精包合物的制备和评价%Preparation and Evaluation of Piroxicam-β-cyclodextrin Inclusion Compound

    Institute of Scientific and Technical Information of China (English)

    吴江; 阮克萍; 张丽珺; 徐白; 方晓玲

    2007-01-01

    将氨水助溶搅拌得到的溶液,分别用冷冻干燥和喷雾干燥法挥去溶剂制备了2种吡罗昔康-β-环糊精包合物,并考察了包合率、粉体学性质、体外溶出速率.结果表明,2种包合物的包合率均大于90%,体外溶出速率显著快于原药和物理混合物.2种包合物具有不同的粉体学性质,表明干燥方法对其有重要影响.本试验制备的2种产物流动性均较差.相较而言,喷雾干燥法制品较有工业化前景.

  4. Preparation and Heat Stability of Piroxicam Polymorphs%吡罗昔康多晶型的制备及其热稳定性

    Institute of Scientific and Technical Information of China (English)

    赵会英; 苏德森; 胡愈; 黄永玲

    2000-01-01

    在不同条件下对吡罗昔康进行了重结晶,经熔点测定、红外光谱、差热分析和粉末X-射线衍射法鉴定,确认吡罗昔康至少存在A、B两种晶型和一个水加合物C.采用差热分析法对A、B和C的热稳定性进行了比较,给出热分解活化能.

  5. The usage of piroxicam and patient dependence: A clinical study%吡罗昔康用法与病人依从性研究

    Institute of Scientific and Technical Information of China (English)

    曹彬; 陈林果

    2007-01-01

    目的:探讨吡罗昔康治疗类风湿关节炎的最佳方法.方法:根据半衰期与稳态血药浓度原理,将门诊类风湿性关节炎病人随机分为试验组和对照组各50例.试验组在第一个半衰期剂量加倍;对照组采用常规治疗法.结果:坚持治疗率试验组为85.4%,对照组为57.8%,经四格表资料x2检验P<0.01.结论:第一个半衰期剂量加倍法可明显提高类风湿关节炎病人的依从性.

  6. IMPROVEMENT OF THE METHOD FOR THE ASSAY OF PIROXICAM TABLETS%吡罗昔康片含量测定方法的改进

    Institute of Scientific and Technical Information of China (English)

    吴静; 王卫平; 吴青

    2001-01-01

    目的:改进吡罗昔康片的含量测定方法.方法:采用紫外分光光度法,用0.1mol·L-1氢氧化钠溶液作溶剂,测定波长为353nm.结果:该法的平均回收率为100.2%,RSD为0.26%.结论:方法简便,准确,所用试剂价廉,无毒害.

  7. P(AA-co-PEGLA)凝胶对吡罗昔康的控释作用%Controlled Release of Piroxicam with P(AA-co-PEGLA) Hydrogels

    Institute of Scientific and Technical Information of China (English)

    马静; 刘新星; 杨植文; 童真

    2009-01-01

    将两亲性大单体聚氧乙烯月桂醇醚丙烯酸酯(PEGLA)与丙烯酸(AA)通过UV引发聚合,制备了水凝胶P(AA-CO-PEGLA).以水难溶性吡罗昔康为模型药物,研究了凝胶中PEGLA含量对栽药量的影响.结果表明;吡罗昔康的栽药量随着PEGLA含量的增加而提高,当凝胶中的PEGLA的摩尔分数(x)从0增加到60%时,载药量从1.24 mg/g提高到17.36 mg/g.吡罗昔康体外释放研究表明:P(AA-co-PEGLA)凝胶可保护药物不被胃酸等破坏,而在肠中释放.药物的释放速率随着凝胶中PEGLA含量的增加而降低,表现出明显的缓释作用.用Weibull方程拟合释放曲线,指数因子(b)0.88~0.97,表明对吡罗昔康释放的控制是扩散和高分子链松弛协同作用的结果.

  8. 不除糖衣测定吡罗昔康片的含量%Study on Assay Method of Piroxicam Tablets without Removing of Sugar Coat

    Institute of Scientific and Technical Information of China (English)

    高立金; 李丽华; 苗起祥

    2001-01-01

    @@ 吡罗昔康片的含量测定方法[1]采用紫外法,但因糖衣片型小,测定时需除去糖衣,不仅费时费力,而且影响到测定的准确性,我们采用不除糖衣直接测定,结果表明糖衣对吡罗昔康片含量测定无显著影响.

  9. 吡罗昔康镝配合物的合成与表征%Synthesis and characterization of the complex of piroxicam and dysprosium

    Institute of Scientific and Technical Information of China (English)

    张艳军; 石俊; 孙体健; 徐隋意; 曹晓峰

    2009-01-01

    利用热乙醇搅拌法合成吡罗昔康和稀土金属镝的配合物,通过紫外光谱、红外光谱、元素分析、电导率、差热-热重等方法对其进行表征,最后确定其组成为Dy(pir)2C2H5OHCl3·2H2O.

  10. 吡罗昔康镧配合物的合成与表征%Synthesis,characterization of the complexe of piroxicam and lanthanum(La)

    Institute of Scientific and Technical Information of China (English)

    张艳军

    2010-01-01

    本论文合成了吡罗昔康和稀土金属镧的配合物,通过紫外光谱、红外光谱、元素分析、电导率、差热一热重等方法对其进行了表征,最后确定其组成为La(pir)2C2H5OHCI3·2H2O.

  11. 吡罗昔康胃肠道安全性数据回顾%The Review of the Gastrointestinal Safety of Piroxicam

    Institute of Scientific and Technical Information of China (English)

    张亚同; 傅得兴; 纪立伟; 刘治军; 孙春华

    2008-01-01

    非选择性非甾体抗炎药吡罗昔康的胃肠道不良反应一直受到关注.通过检索PUBMED数据库,结合手工筛选和PUBMED自带的相似文献检索,以及检索Cochrane,查找有关吡罗昔康不良反应和安全性内容的个案和综述文献,并结合最近的相关新闻报道进行总结分析,结果表明吡罗昔康属于胃肠道安全性较差的非甾体抗炎药物.

  12. 吡罗昔康胶囊体外溶出速率的实验%Study on the of dissolution rate of Piroxicam in entecavir capsules

    Institute of Scientific and Technical Information of China (English)

    陈向前; 张青

    2010-01-01

    目的 研究吡罗昔康胶乓体外溶出速率的方法.方法 溶出度测定法(附录XCD第二法,溶出介质为0.1md·L-1盐酸溶液,吡罗昔康胶囊的溶出量采用高效液相色谱法测定.结果 吡罗昔康浓度在1.5~3.5μg·mL-1范围内与各自的峰面积呈良好的线性关系,r为0.9998.平均回收率为99.7%,RSD0.5%.该样品30min溶出量就在90%以上.结论 本方法用于吡罗昔康胶囊中吡罗昔康的溶出度测定切实可行.

  13. Rapid Detection of Piroxicam and Meloxicam%吡罗昔康与美洛昔康的快速检测

    Institute of Scientific and Technical Information of China (English)

    刘惠民; 王仕平; 刘卿

    2010-01-01

    目的 建立抗风湿类中成药中非法添加化学成分吡罗昔康与美洛昔康的快速检测方法.方法 采用化学鉴别方法 进行快速筛查,并用薄层色谱法进行进一步确认验证.结果 化学鉴别与薄层色谱法能快速准确的检测出抗风湿类中成药中非法添加化学成分吡罗昔康与美洛昔康.结论 本方法 简便、快速、准确、专属性强,可用于抗风湿类中成药中非法添加的吡罗昔康与美洛昔康的快速检测,并且还能够在基层及国家配备的快检车上应用.

  14. Preparation of Inclusion Complex of Piroxicam with β-Cyclodextrin%吡罗昔康-β-环糊精包合物的制备研究

    Institute of Scientific and Technical Information of China (English)

    陈寅生; 陈洪轩; 马莉

    2008-01-01

    目的 将吡罗昔康与β-环糊精制备成包合物,降低其对胃肠道的刺激性.方法 采用饱和水溶液法,以收率和包合率为指标,用正交试验设计法筛选最佳包合条件,然后用显微镜法和X-射线衍射法分别对制备的包合物进行鉴定.结果 最佳包合条件是吡罗昔康与β-环糊精的物质的量比为1:2.5.包合温度50℃,包合时间6h,搅拌速度600 r/min;经显微镜法和X-射线衍射法鉴定,形成了吡罗昔康-β-环糊精包合物.结论 用饱和水溶液法制备吡罗昔康-β-环糊精包合物,收率和包合率都较高,且操作方法简单易行.

  15. HPLC法测定吡罗昔康片中吡罗昔康的含量%Determination of piroxican in piroxicam tablets by HPLC

    Institute of Scientific and Technical Information of China (English)

    吴红英; 徐道华; 邱栋樑

    2009-01-01

    目的 建立 HPLC 测定吡罗昔康片的方法.方法 采用 Agilent Eclipse XDB-C18色谱柱,甲醇-0.025 mmol·L-1磷酸溶液(三乙胺调节pH=3.0)-乙腈(50:35:15)为流动相,柱温:22℃,检测波长为334 nm,流速1.0 ml·min-1.结果 吡罗昔康在0.0390~0.7792 μg范围内与峰面积呈良好的线形关系(r=1.000 0);平均回收率为99.00%,RSD=0.41% (n=6).结论 本方法简便、准确、重现性好,可用于该制剂的质量控制.

  16. 甲酚红褪色分光光度法测定吡罗昔康%Fading spectrophotometric method for the determination of Piroxicam

    Institute of Scientific and Technical Information of China (English)

    金迎春; 敖登高娃

    2010-01-01

    用褪色分光光度法(测定药物制剂和生物样品中吡罗昔康含量.)在Ph8.75的tris-HCl缓冲溶液中,甲酚红与吡罗昔康反应形成离子缔合物,使甲酚红溶液褪色,最大褪色波长位于570nm,吡罗昔康浓度在0.06628~11.60 μg/Ml范围内遵循比尔定律,回归方程为ΔA=0.1404c+0.0067,相关系数为r=0.9996,表观摩尔吸光系数为4.703×104 L·mol-1·cm-1.据此建立了方法,样品测定平均回收率为97.51%~101.4%.

  17. Preparation and Quality Control of Piroxicam Plastics%吡罗昔康涂膜剂的制备与质量控制

    Institute of Scientific and Technical Information of China (English)

    张红; 刘宾; 何伟雄

    2009-01-01

    目的 制备吡罗昔康涂膜剂,建立其质量控制方法 .方法 选用壳聚糖和羧甲基纤维素钠为成膜材料制备吡罗昔康涂膜剂,采用高效液相色谱(HPLC)法测定吡罗昔康含量.结果 吡罗昔康的质量浓度线性范围为10.0~90.0 μg/mL,平均回收率为100.09%,RSD为0.56%(n=6).结论 该制剂性质稳定,质控方法 可行,能达到质量控制要求.

  18. 毛细管电泳法测定吡罗昔康的含量%Determination of Piroxicam Content with Capillary Electrophoresis

    Institute of Scientific and Technical Information of China (English)

    江银枝; 张丽; 周利强

    2014-01-01

    建立高效毛细电泳法来测定吡罗昔康含量.采用毛细管电泳仪进行实验:弹性石英毛细管柱75 μm×60 cm,进样压力100 mPa,电动进样5 s,分离电压24 kV,毛细管温度20℃,检测波长为254 nm,运行缓冲液为0.01mol/L硼砂溶液.采用t法和F法进行与HPLC法的显著性检验.吡罗昔康样品的线性范围:1.0×10-6~1.0×10-2 mol/L,回收率:98.66%,RSD=2.1%,与HPLC法无显著性差异.实验表明毛细管电泳法分离效率高、分析速度快、样品和试剂用量少.

  19. 吡罗昔康乳膏的制备及稳定性研究%Research on preparation and stability of piroxicam cream

    Institute of Scientific and Technical Information of China (English)

    黎碧云; 谢根英; 林碧英; 丘静艳

    2008-01-01

    目的 吡罗昔康乳膏的研制及稳定性研究.方法 采用正交设计法对处方基质进行优选并进行稳定性考察.结果 得到最优基质配比:十二烷基硫酸钠为5%、硬脂酸为10%、吐温-80为4%、三乙醇胺为1%.结论 吡罗昔康乳膏性质稳定,达到了质量标准的要求.

  20. 吡罗昔康的荧光分光光度法测定%Determination of piroxicam with fluorescence spectrophotometry

    Institute of Scientific and Technical Information of China (English)

    郝巧艳; 张远馥; 王金中

    2007-01-01

    目的 以荧光分光光度法为基础建立测定片剂中吡罗昔康含量的新方法.方法 基于在pH=3.6的弱酸性介质中,吡罗昔康能够阻抑K2S2O8氧化荧光桃红的荧光淬灭反应.结果 吡罗昔康的质量浓度与荧光强度的变化在0.1~2.0 μg/mL范围内呈良好线性关系,相对标准偏差(RSD)为3.12%,该方法的检出限为4.5×10-2 μg/mL.结论 该法简便、快速,结果可靠,并应用于药物制剂中吡罗昔康含量的测定,结果令人满意.

  1. 吡罗昔康乳膏的制备及稳定性考察%Research on the Preparation of Piroxicam Cream and its Stability

    Institute of Scientific and Technical Information of China (English)

    康艳萍; 刘紫英

    2008-01-01

    目的 吡罗昔康乳膏的制备及稳定性研究.方法 采用正交设计法时处方基质进行优选并进行初步稳定性考察.结果 得到最优基质配比:十二烷基硫酸钠为0.5%,硬脂酸为10%,吐温-80为4%,三乙醇胺为1%.结论 吡罗昔康乳膏性质稳定.达到了乳膏质量标准的要求.

  2. The Preparation and Clinical Effects of Piroxicam Liniment%吡罗昔康搽剂的研制及临床疗效

    Institute of Scientific and Technical Information of China (English)

    许鲁宁; 黄跃; 黄芳

    2004-01-01

    目的降低吡罗昔康消化系统副作用,满足风湿性类风湿性关节炎患者长期局部使用本品的目的.方法首先对处方中透皮吸收剂的种类及浓度、助溶剂的用量等因素进行考察,确定最优组方,按筛选出处方配制吡罗昔康搽剂并观察临床疗效.结果所得搽剂无刺激性、质量可控,经临床使用总有效率达97%.结论本搽剂不仅适宜于医院小量配制,也适宜于药厂大批量生产,大大提高了本品的临床应用价值.

  3. Study on percutaneous permeation of piroxicam and in-vitro evalution of piroxicam gels for transdermal delivery%透皮促进剂对吡罗昔康经皮渗透的影响及吡罗昔康凝胶剂体外透皮性质评价

    Institute of Scientific and Technical Information of China (English)

    董平; 沈蕴琪; 沙先谊; 方晓玲

    2010-01-01

    目的 考察透皮促进剂对吡罗昔康体外经皮渗透的影响,制备吡罗昔康凝胶并评价该制剂的经皮渗透特性.方法 以大鼠皮肤作为试验材料,HPLC法测定药物浓度,采用智能透皮试验仪考察吡罗昔康经皮渗透参数.结果 月桂氮草酮、薄荷醇、尿素均能促进吡罗昔康的渗透,其中月桂氮草酮和丙二醇联合应用时,促透效果最好;以羟丙基纤维素为基质的吡罗昔康凝胶比以卡波姆为基质的凝胶渗透效果好.结论 选用月桂氮草酮与丙二醇为透皮促进剂,以羟丙基纤维素为基质制备的吡罗昔康凝胶剂,药物的经皮渗透性最佳.

  4. Drug: D05512 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available i-inflammatory ATC code: M01AC01 M02AA07 cyclooxygenase-1 (COX-1) inhibitor [HSA:5742] [KO:K00509]; cyclooxygenase...m D05512 Piroxicam cinnamate (USAN) Target-based classification of drugs [BR:br08310] Enzymes Oxidoreductases cyclooxygenase...-1 (COX-1) [HSA:5742] [KO:K00509] Piroxicam [ATC:M01AC01 M02AA07 S01BC06] D05512 Piroxicam cinnamate (USAN) cyclooxyg...enase-2 (COX-2) [HSA:5743] [KO:K11987] Piroxicam [ATC:M01AC01 M02AA07 S01BC06] D055

  5. Pectin/zein hydrogels for the delivery of drugs and nutrients

    Science.gov (United States)

    Two pectin/zein coacervates were prepared with either calcium ions or zinc ions. Piroxicam, a non-steroidal anti-inflammatory drug, was encapsulated. It was found that at lower solution pH the release of piroxicam displayed a near zero order kinetics, whether the coacervates were cross-linked with c...

  6. A long-term randomised trial on tenoxicam and piroxicam in osteoarthritis of the hip or knee: a 24-month interim report focusing on the 12-24 month interval

    DEFF Research Database (Denmark)

    Lund, B; Andersen, R B; Fossgreen, J

    1987-01-01

    or knee have been reported. This interim analysis focuses mainly on the 12 to 24 month interval. The clinical improvements obtained within the first 12 months persisted during the second year in the 55 patients remaining on treatment. After 24 months, 53 patients had been withdrawn prematurely, three...

  7. Pharmacokinetics of imported piroxicam patches after continuous transdermal administration in Chinese healthy volunteers%进口吡罗昔康贴片连续用药的人体药动学

    Institute of Scientific and Technical Information of China (English)

    胡晓; 熊玉卿

    2010-01-01

    目的:研究吡罗昔康贴片在中国健康志愿者体内连续给药的药动学.方法:11名健康受试者连续使用吡罗昔康贴片,每2天1次,每次1片(48 mg),连续使用14 d,HPLC法测定血液中吡罗昔康的浓度,用DAS软件进行数据处理,计算药动学参数.结果:连续使用吡罗昔康贴片第10天,其血药浓度已达稳态.主要药动学参数tmax为(43.8±15.5)h,Cmax为(40.6±11.3)μg·L-1,t1/2为(62.3±23.7)h,AUC0-τ和AUC0-∞分别为(4177.3±1376.0)μg·L-1·h和(5867.9±2768.7)μg·L-1·h,波动度为1.09±0.24.和受试者单次使用同等剂量贴片的药动学参数值进行组间t检验,结果差异无统计学意义.结论:吡罗昔康贴片按每2天1次,每次1片试验方案给药,在国人体内不产生蓄积现象,且受试者情况良好未发生任何不良反应.

  8. 吡罗昔康贴片在膝关节置换术后镇痛效果研究%The analgesia effect of piroxicam patches on total knee arthroplasty

    Institute of Scientific and Technical Information of China (English)

    辛鹏; 张国强; 柴伟; 倪明; 王岩

    2016-01-01

    目的 研究吡罗昔康贴片用于人工全膝关节置换围手术期的镇痛效果.方法 选取本科2014年3月~12月入院在全麻下行单侧初次人工全膝关节置换术的骨关节炎患者218例,以随机数字表按简单随机分组法分为吡罗昔康组109例和对照组(不使用吡罗昔康)109例,比较两组患者术后疼痛视觉模拟评分(visual analog scale,VAS)和主、被动关节活动度(range of motion,ROM)及术后不良反应、补充性镇痛、镇痛满意度以评价临床镇痛效果.结果 两组患者在年龄、身高、体质量、体质量指数、性别、假体、膝关节HSS评分、术前ROM、术前行走VAS、手术时间方面均未见统计学差异.两组术后静息与运动VAS评分、主动活动度、术后补充性镇痛差异均有统计学意义(P≤0.05).两组患者术后住院天数、不良反应发生率、术后满意度差异无统计学意义(P>0.05).结论 术后外用吡罗昔康贴片对于初次人工全膝关节置换术术后早期镇痛效果明显,改善关节主动活动度,且术后补充性镇痛应用较少.可与全身药物联合应用,缓解膝关节置换术后疼痛.

  9. DETERMINATION OF INDOMETACIN AND PIROXICAM IN LONGDAN FENGSHI CAPSULES BY HPLC%高效液相色谱法测定龙胆风湿胶囊中吲哚美辛和吡罗昔康的含量

    Institute of Scientific and Technical Information of China (English)

    符洪; 鲁秋红

    2002-01-01

    目的:建立龙胆风湿胶囊中吲哚美辛和吡罗昔康的含量测定方法.方法:反相高效液相色谱法.选用大连依利特公司的C18分析柱(200mm× 4.6mm,10μm),流动相:乙腈-磷酸盐缓冲液(pH=5.0)(40:60),检测波长:254nm,流速:1.0ml/min-1.结果:本法简便、灵敏、准确.线性范围:吲哚美辛、吡罗昔康分别为0.46~4.60μg(r=0.9999),0.39~1.36μg(r=0.9999).平均回收率分别为100.3%(RSD=0.68)和101.6%(RSD=1.82).结论:本文建立的高效液相色谱法,为测定龙胆风胶囊中的吲哚美辛和吡罗昔康的含量提供了可靠的分析方法.

  10. 仙草风湿胶囊中吲哚美辛和吡罗昔康的含量测定%Determination of Indometacin and Piroxicam in Xianchao Fengshi Capsules

    Institute of Scientific and Technical Information of China (English)

    鲁秋红; 符洪; 谢世祺

    2002-01-01

    目的:采用双波长分光光度法和单波长分光光度法测定仙草风湿胶囊中吲哚美辛和吡罗昔康的含量.方法:利用吲哚美辛和吡罗昔康溶解性能,采用氯仿溶解,碱液提取,用双波长分光光度法和单波长分光光度法,分别测定吲哚美辛和吡罗昔康的含量.结果:吲哚美辛和吡罗昔康的平均回收率分别为99.7%和100.7%,RSD分别为0.72%和0.86%.结论:方法简便,可靠,重现性好,可消除中药成分的干扰.

  11. HPLC法检测抗风湿类中成药中添加的尼美舒利和吡罗昔康%Determination of Adding Nimesulide and Piroxicam in Antirheumatic class traditional Chinese medicine by HPLC

    Institute of Scientific and Technical Information of China (English)

    郭飞宇; 李存金

    2010-01-01

    目的:建立HPLC法检测抗风湿类中成药中非法添加化学物质尼美舒利和吡罗昔康的检验方法.方法:采用Diamonsil C18色谱柱,流动相:甲醇-1.36g/L磷酸二氢钾溶液(54∶46),流速:1.0 ml/min,柱温:25 ℃,检测波长:338 nm.结果:尼美舒利对照品线性范围150.06~400.16 μg/ml,r=0.999 9;吡罗昔康对照品线性范围42.24~112.64 μg/ml,r=0.999 9.平均回收率分别为98.74%,99.04%,RSD分别为0.7%,0.9%(n=6).结论:本方法灵敏度高,操作简便、准确,可用于定性和定量检测抗风湿类中成药中非法添加的化学物质尼美舒利和吡罗昔康.

  12. 高效液相色谱法测定吡罗昔康片的有关物质%Determination of Related Substances in Piroxicam Tablets by HPLC

    Institute of Scientific and Technical Information of China (English)

    李玲; 姜燕; 陈乃江

    2016-01-01

    目的:建立测定吡罗昔康片有关物质的高效液相色谱法。方法采用C18色谱柱(250mm ×4.6mm,5μm),流动相为乙腈-0.05mol· L -1磷酸二氢钾溶液(用磷酸调节pH至3.0)(35∶65),流速1.0mL· min -1,检测波长为230nm,柱温为40℃,进样体积为20μL。结果在选定的色谱条件下,主成分与杂质峰之间分离度良好;方法的检测限为0.3μg· mL -1;供试品溶液在20h内稳定性良好。结论本方法简单,准确,重现性好,可用于吡罗昔康片的有关物质检查。

  13. HPLC法检验骨刺消痛胶囊中非法添加西药吡罗昔康%Determination of Piroxicam Adding Illegally in Guci Xiaotong Capsules by HPLC

    Institute of Scientific and Technical Information of China (English)

    赵艳; 付艳敏; 李伯军; 李冬梅

    2009-01-01

    目的 建立HPLC法检验骨刺消痛胶囊中非法添加西药吡罗昔康的检验方法.方法 采用shim-pack C18色谱柱,流动相:乙腈-0.5%冰醋酸溶液(60∶40);检测波长:243nm.结果 吡罗昔康对照品线性范围1.068~53.40μg·mL-1,r2=1,平均回收率为98.9%,RSD为2.1%(n=6).结论 定量方法简便,准确,专属性强.能有效地控制制剂的质量,打击假劣药品.

  14. Improvement of dissolution rate of piroxicam by assembling into SBA-15 mesoporous silica%有序介孔材料SBA-15提高难溶性药物吡咯昔康溶出度的研究

    Institute of Scientific and Technical Information of China (English)

    付廷明; 乐康; 陆瑾; 王天瑶; 郭立玮

    2010-01-01

    目的 采用与介孔材料复合的方式提高难溶性药物吡咯昔康的溶出度.方法 通过X射线衍射、氮气吸附-脱附曲线、热分析及溶出度实验,观察吡咯昔康负载到SBA-15的表面情况.结果 吡咯昔康溶解后自组装在介孔材料SBA-15的表面,紫外吸收与热重分析表明负载量为17%;X射线衍射、氮气吸附-脱附曲线、热分析及溶出度实验表明:吡咯昔康以极小非晶的形式负载在SBA-15的表面,负载后吡咯昔康的溶出度提高了144%.结论 本研究为提高难溶性药物的溶出度提供了一条新途径.

  15. 热熔挤出技术制备吡罗昔康固体分散体%Preparation of Piroxicam Solid Dispersion by hot-melt extrusion technology

    Institute of Scientific and Technical Information of China (English)

    张庆刚; 赵星星

    2013-01-01

    目的 采用热熔挤出技术制备难溶性药物吡罗昔康固体分散体,来提高其溶出速率.方法 以共聚维酮(PVP-VA64)为亲水性载体材料,聚乙二醇6000为增塑剂,采用热熔挤出技术制备吡罗昔康固体分散体.通过比较差示扫描量热图谱和累积溶出曲线,来表征和评价所制备的固体分散体.结果 所制备的固体分散体溶出速率较物理混合物均显著提高.结论 热熔挤出技术适用于制备吡罗昔康固体分散体,药物是以无定型分散在载体中,溶出度得到显著提高.

  16. HPLC测定吡罗昔康注射液含量及有关物质%Determination of the Content and the Related Substances of Piroxicam Injection by HPLC

    Institute of Scientific and Technical Information of China (English)

    刘洪海

    2015-01-01

    目的 建立高效液相色谱法测定吡罗昔康注射液含量及有关物质.方法 色谱柱为Inertsil ODS-SP(4.6 mm×250 mm,5 μm);流动相为甲醇-0.5%冰乙酸溶液(60∶40);流速为0.8mL·min-1;检测波长为338 nm;柱温为30℃.结果 吡罗昔康在0.016~158.7 μ.g·mL-1内呈良好线性关系,r=0.999 8(n=6).高、中、低3个浓度总的平均回收率为99.13%,仪器精密度RSD为0.19%.结论 本方法方便、简单、准确,适于吡罗昔康注射液含量及有关物质的测定.

  17. 小针刀结合臭氧治疗桡骨茎突狭窄性腱鞘炎临床研究%Clinical Research of Acupotomy Combined with Piroxicam Patches in Treatment of Stenosing Tendovaginitis of Radial Styloid

    Institute of Scientific and Technical Information of China (English)

    张董喆; 孔超; 于世超; 张建福

    2016-01-01

    目的:观察小针刀结合臭氧治疗桡骨茎突狭窄性腱鞘炎的临床疗效.方法:60例桡骨茎突狭窄性腱鞘炎患者随机分为两组.治疗组30例采用小针刀结合臭氧,对照组30例采用封闭注射.观察两组治疗前后的临床疗效.结果:治疗后视觉模拟评分(visual analog scale,VAS)治疗组为(2.14±0.58)分,对照组为(3.47±1.14)分,两组比较,差异有统计学意义(P<0.01);治疗组有效率为90%,对照组有效率为67%,两组比较,差异有统计学意义(P<0.05).结论:小针刀结合臭氧疗效较单纯封闭注射治疗效果好,能有效缓解症状和疼痛.

  18. Determination of Gelatim Piroxicam by Ultra-Violet Spectrophotometry%吡罗昔康凝胶有效成分的紫外分光光度法测定

    Institute of Scientific and Technical Information of China (English)

    陈浩; 刘万忠; 糜志远

    2000-01-01

    吡罗昔康凝胶是吡罗昔康加适量的基质制成的透明的透皮吸收制剂.本文提出了对其有效成分吡罗昔康进行紫外分光光度测定的方法.该方法简便、快速,能用于纯度较高的样品分析,可作为吡罗昔康凝胶药品质量标准控制方法.

  19. The Clinical Research of Piroxicam Patches in Treating on Knee Osteoarthritis Patients under Biomechanics Principle%生物力学敷贴吡罗昔康治疗膝骨关节炎研究

    Institute of Scientific and Technical Information of China (English)

    方春养

    2011-01-01

    目的 观察生物力学辨证下吡罗昔康贴片治疗膝骨关节炎的临床疗效,并探讨其作用机制.方法 将膝骨关节炎患者100例随机分成治疗组和对照组,每组50例,治疗组按生物力学辨证敷贴吡罗昔康贴片于治疗点,对照组给予扶他林乳胶剂,连续用药12周.观察治疗前后靶部位的VAS评分、体征等指标及总体评价.结果 治疗组总有效率为90%,对照组总有效率为70%;在功能改善及缓解疼痛情况方面,两组经统计学处理差异有统计学意义(P<0.05),治疗组明显优于对照组.结论 吡罗昔康贴片在改善患者症状体征、提高生活质量方面及减轻疾病活动性方面都具有良好的疗效,并且毒副作用和不良反应小,具有一定的临床应用前景.

  20. 吡罗昔康透皮控释贴片治疗膝骨关节炎的疗效和安全性观察%Efficacy and safety of piroxicam patch for the treatment of knee osteoarthritis

    Institute of Scientific and Technical Information of China (English)

    郭军华; 黄烽; 张江林; 朱剑

    2008-01-01

    目的:观察吡罗昔康透皮控释贴片治疗膝骨关节炎(OA)的疗效和安全性.方法:采用开放试验,观察20例膝骨关节炎患者应用吡罗昔康透皮控释贴片,隔日1贴共12 d的疗效和安全性.主要疗效指标为指定膝关节休息痛和活动痛VAS评分,次要疗效指标包括药物起效时间、疼痛明显缓解时间、患者对疗效的总体评价和压痛及肿胀指数,并记录研究期间的所有不良事件.结果:治疗前患者休息痛和活动痛VAS评分分别为(4.00±3.54)及(6.73±2.12),治疗后分别为(1.98±4.24)及(3.25±4.95)(P<0.01~0.001),患者对疗效的综合评价有效率为100%,显效率为75%.首次给药后疼痛缓解时间平均为(2.95±1.41)d.全部受试者均未出现不良反应.结论:吡罗昔康贴片治疗膝骨关节炎有良好的止痛效果,安全性好.

  1. Improvement in Dissolution Properties of piroxicam by Complexation with β- Cyclodextrin and PVP%固体分散技术与包合技术对吡罗昔康溶出度的影响

    Institute of Scientific and Technical Information of China (English)

    胡鹏翼; 易以木

    2007-01-01

    目的 考察固体分散技术及包合技术对吡罗昔康溶出度的影响.方法 以聚乙烯吡咯烷酮(PVP)为载体制备固体分散体;以β-环糊精(β-CD) 包合技术制备包合物.以差示扫描量热法(DSC)鉴定吡罗昔康在体系中的存在形态;以水为溶出介质, 紫外分光光度法测定不同制备工艺下成品的体外溶出度.结果 差热分析图谱表明,吡罗昔康β-CD包合物以及吡罗昔康-PVP(1:6,1:8)的固体分散体中药物以非晶型存在,而吡罗昔康-PVP(1:2,1:4)的固体分散体中,药物与载体形成低共熔物,药物以微晶形式存在于载体中;体外溶出结果 表明环糊精包合物和载药比为1:6,1:8的固体分散体的溶出速率与相应物理混合物及原料药间差异有极显著性(P<0.01).结论 制成固体分散体和β-环糊精包合物均能显著提高吡罗昔康的溶出速率.

  2. Study on the inclusion interaction of piroxicam with β-cyclodextrin derivatives%吡罗昔康与β-环糊精的包合作用研究

    Institute of Scientific and Technical Information of China (English)

    孙体健; 刁海鹏; 王茹林; 曹晓峰; 李根; 裴晓丽

    2007-01-01

    目的 旨在研究环糊精衍生物(CDs)与吡罗昔康(PX)的包合作用.方法 采用荧光光谱法研究了PX与β-环糊精(β-CD)、羟丙基-β-环糊精(HP-β-CD)、磺丁醚-β-环糊精(SBE-β-CD)的包合特性.结果 当CDs存在时,PX最大荧光发射波长的变化及荧光强度的增强预示着包合物的形成,并通过荧光光谱法测定CDs与PX的包合常数.结论 由包合常数表明:β-CD对PX的包合能力最强.除了β-CD与PX是以2:1的比例形成包合物外,其余两种包合物都是以1:1的比例包合.

  3. Study on preparation and percutaneous absorption in vitro of piroxicam microemulsion%吡罗昔康外用微乳的制备及其透皮吸收的研究

    Institute of Scientific and Technical Information of China (English)

    董平; 吴娟; 沙先谊; 方晓玲

    2010-01-01

    目的 制备吡罗昔康微乳并考察其体外经皮渗透特性.方法 采用Lauroglycol FCC为油相、Labrasol、Cremophor EL为表面活性剂、Transcutol P、乙醇为助表面活性剂,绘制伪三元相图,制备吡罗昔康O/W微乳.采用智能透皮实验仪,大鼠背部皮肤作为透皮模型, HPLC测定药物透皮浓度, 研究吡罗昔康微乳的透皮特性.结果 本实验中微乳较优处方含:吡罗昔康0.5%,Lauroglycol FCC10%,Labrasol、Cremophor EL、Transcutol P各13.3%及水50%,吡罗昔康渗透速率可达10.04±1.73 μg/(cm2·h).结论 吡罗昔康微乳有很强的透皮能力,有望成为吡罗昔康的新型透皮给药制剂.

  4. The percutaneous absorption potential of two kinds of piroxicam gels:a comparative study in vitro%两种吡罗昔康凝胶体外经皮行为的比较

    Institute of Scientific and Technical Information of China (English)

    董平; 孟现民; 沙先谊; 方晓玲

    2010-01-01

    目的:比较两种吡罗昔康凝胶的体外透皮吸收情况.方法:采用智能透皮试验仪对吡罗昔康凝胶进行体外经皮渗透实验,采用HPLC法测定透过离体大鼠皮肤的吡罗昔康含量.结果:样品A透皮速率达到(57.33±3.23)μg/(cm2·h),明显优于样品B(P<0.01).结论:不同厂家的吡罗昔康凝胶剂经皮性质差异显著.

  5. The Influence of PVP and PEG on Piroxicam β-Cyclodextyin Inclusion Action%聚维酮和聚乙二醇对吡罗昔康-β-环糊精包合的影响

    Institute of Scientific and Technical Information of China (English)

    王齐放; 修锐; 赵哲; 郭晶; 苏德森

    2000-01-01

    研究了聚乙烯吡咯烷酮(PVPK-30)和聚乙二醇(PEG-4000)对吡罗昔康-β-环糊精包合作用的影响,用热力学的方法求出了包合物在高聚物存在下的热力学函数.结果表明,吡罗昔康-β-环糊精包合物在PVP和PEG的存在下包合反应表观稳定常数(KC)增大,包合反应的自由焓(ΔG)减小.高聚物的最佳浓度为3~5 g /L.

  6. 吡罗昔康普朗尼克磷脂有机凝胶的体外评价和局部组织分布%In vitro evaluation and local tissue distribution of piroxicam Pluronic lecithin organogel

    Institute of Scientific and Technical Information of China (English)

    杨艳丽; 徐晖; 盛秋双; 王晓芸; 郭建博; 郑俊民

    2009-01-01

    目的 制备普朗尼克磷脂有机凝胶,以吡罗昔康为模型药物,评价其体外性能并考察其局部组织分布特征.方法 应用椎-板模型流变仪测定普朗尼克磷脂有机凝胶的流变学参数,Franz扩散池法测试其体外释放和经皮通透性,考察大鼠局部给药的局部组织分布.结果 普朗尼克磷脂有机凝胶具有典型的凝胶的流变学特征;48 h体外累积释放率和经皮通透率分别为(81.56±3.09)%和(3.80±1.59)%;皮肤和肌肉的药时曲线具有双峰特征,给药侧的组织药物浓度高于血药浓度和对侧相同组织的浓度,原因在于药物的直接通透和系统再分布.结论 普朗尼克磷脂有机凝胶适用于皮肤局部给药的载体.

  7. Template occluded SBA-15: An effective dissolution enhancer for poorly water-soluble drug

    Energy Technology Data Exchange (ETDEWEB)

    Fu Tingming, E-mail: futingming@gmail.com [College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029 (China); Guo Liwei; Le Kang; Wang Tianyao; Lu Jin [College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029 (China)

    2010-09-15

    The aim of the present work was to improve the dissolution rate of piroxicam by inclusion into template occluded SBA-15. Our strategy involves directly introducing piroxicam into as-prepared SBA-15 occluded with P123 (EO{sub 20}PO{sub 70}EO{sub 20}) by self assembling method in acetonitrile/methylene chloride mixture solution. Ultraviolet spectrometry experiment and thermogravimetric analysis-differential scanning calorimetry (TG-DSC) profiles show that the piroxicam and P123 contents in the inclusion compound are 12 wt% and 28 wt%, respectively. X-ray powder diffraction and DSC analysis reveal that the included piroxicam is arranged in amorphous form. N{sub 2} adsorption-desorption experiment indicates that the piroxicam has been introduced to the mesopores instead of precipitating at the outside of the silica material. The inclusion compound was submitted to in vitro dissolution tests, the results show that the piroxicam dissolve from template occluded inclusion compound more rapidly, than these from the piroxicam crystalline and template removed samples in all tested conditions. Thus a facile method to improve the dissolution rate of poorly water-soluble drug was established, and this discovery opens a new avenue for the utilization of templates used for the synthesis of mesoporous materials.

  8. Template occluded SBA-15: An effective dissolution enhancer for poorly water-soluble drug

    Science.gov (United States)

    Tingming, Fu; Liwei, Guo; Kang, Le; Tianyao, Wang; Jin, Lu

    2010-09-01

    The aim of the present work was to improve the dissolution rate of piroxicam by inclusion into template occluded SBA-15. Our strategy involves directly introducing piroxicam into as-prepared SBA-15 occluded with P123 (EO 20PO 70EO 20) by self assembling method in acetonitrile/methylene chloride mixture solution. Ultraviolet spectrometry experiment and thermogravimetric analysis-differential scanning calorimetry (TG-DSC) profiles show that the piroxicam and P123 contents in the inclusion compound are 12 wt% and 28 wt%, respectively. X-ray powder diffraction and DSC analysis reveal that the included piroxicam is arranged in amorphous form. N 2 adsorption-desorption experiment indicates that the piroxicam has been introduced to the mesopores instead of precipitating at the outside of the silica material. The inclusion compound was submitted to in vitro dissolution tests, the results show that the piroxicam dissolve from template occluded inclusion compound more rapidly, than these from the piroxicam crystalline and template removed samples in all tested conditions. Thus a facile method to improve the dissolution rate of poorly water-soluble drug was established, and this discovery opens a new avenue for the utilization of templates used for the synthesis of mesoporous materials.

  9. The effect of non-steroidal anti-inflammatory drugs on the metabolism of /sup 14/C-arachidonic acid by human gingival tissue in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Elattar, T.M.; Lin, H.S.; Tira, D.E.

    1983-09-01

    We investigated the effect of non-steroidal anti-inflammatory drugs on prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid (12-HETE) formation by inflamed human gingival tissues. Gingival tissue homogenates were incubated with /sup 14/C-arachidonic acid in the presence of indomethacin, piroxicam, or ibuprofen, and the organic solvent extracts were chromatographed on silica gel plates with standards for radiometric assay. There was a significant negative trend between the doses (10(-7)-10(-3) M) of each of indomethacin, piroxicam, and ibuprofen, and the amounts of PGF2 alpha, PGE2, PGD2, and 15-keto-PGE2 produced. All three drugs have a significant inhibitory effect on PGs and 12-HETE production at 10(-3) M when compared with the control. The rank order effectiveness of the drugs, at 10(-3) M, on PG inhibition was indomethacin greater than piroxicam greater than ibuprofen, and on 12-HETE inhibition was indomethacin greater than ibuprofen greater than piroxicam.

  10. A comparative study of efficacy and safety of flupirtine versus piroxicamin patients with low back pain

    Directory of Open Access Journals (Sweden)

    Ambrish Sharma

    2015-09-01

    Results: 74 patients were randomized to 2 groups of 37 each. Group I patients received flupirtine maleate 100 mg twice daily and Group II patients received piroxicam 20 mg twice daily for 14 days. 30 patients in each group completed the study and were analysed. On intergroup comparison, there was no statistical difference (p>0.05 in the efficacy parameters of finger-to-floor distance (FFD, lumbar pain, Lasegue's sign, tenderness of vertebral muscles, sensory disturbance in lower limbs, VAS scores and global assessment of response to therapy. 13.3% in flupirtine group and 16.6% in piroxicam group reported adverse events. Conclusions: Both flupiritine and piroxicam were equally effective but flupirtine was better tolerated than piroxicam. [Int J Res Med Sci 2015; 3(9.000: 2337-2341

  11. Drug: D05513 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available if Analgesic; Anti-inflammatory ATC code: M01AC01 M02AA07 cyclooxygenase-1 (COX-1) inhibitor [HSA:5742] [KO:K00509]; cyclooxygenase...rget-based classification of drugs [BR:br08310] Enzymes Oxidoreductases cyclooxygenase-1 (COX-1) [HSA:5742] ...[KO:K00509] Piroxicam [ATC:M01AC01 M02AA07 S01BC06] D05513 Piroxicam olamine (USAN) cyclooxygenase-2 (COX-2)

  12. Prediction of dissolution-absorption relationships from a dissolution/Caco-2 system.

    Science.gov (United States)

    Ginski, M J; Polli, J E

    1999-01-15

    While the analysis of in vitro dissolution-in vivo absorption relationships from oral solid dosage forms provides biopharmaceutical insight and regulatory benefit, no well developed method exists to predict dissolution-absorption relationships a priori to human studies. The objective was to develop an integrated dissolution/Caco-2 system to predict dissolution-absorption relationships, and hence the contributions of dissolution and intestinal permeation to overall drug absorption for fast and slow formulations of piroxicam, metoprolol, and ranitidine. Dissolution studies were conducted on fast and slow dissolving immediate-release formulations of piroxicam, metoprolol tartrate, and ranitidine HCl. Dissolution samples were treated with concentrated buffers to render them suitable (i.e., isotonic and neutral pH) for Caco-2 monolayer permeation studies. The dissolution/Caco-2 system yielded a predicted dissolution-absorption relationship for each formulation which matched the observed relationship from clinical studies. The dissolution/Caco-2 system's prediction of dissolution or permeation rate-limited absorption also agreed with the clinical results. For example, the dissolution/Caco-2 system successfully predicted the slow piroxicam formulation to be dissolution rate-limited, and the fast piroxicam formulation to be permeation rate-limited. Moreover, the system predicted this change from dissolution rate-limited absorption for slow piroxicam to permeation rate-limited absorption for fast piroxicam, in spite of piroxicam's high permeability and low solubility. The dissolution/Caco-2 system may prove to be a valuable tool in formulation development. Broader evaluation of such a system is warranted.

  13. Prediction of dissolution-absorption relationships from a continuous dissolution/Caco-2 system.

    Science.gov (United States)

    Ginski, M J; Taneja, R; Polli, J E

    1999-01-01

    The objectives were 1) to design a continuous dissolution/Caco-2 system to predict the dissolution-absorption relationships for fast and slow dissolving formulations of piroxicam, metoprolol tartrate, and ranitidine HCl, and compare the predicted relationships with observed relationships from clinical studies; 2) to estimate the effect of croscarmellose sodium on ranitidine dissolution-absorption relationships; and 3) to estimate the effect of solubilizing agents on piroxicam dissolution-absorption relationships. A continuous dissolution/Caco-2 system was constructed from a dissolution apparatus and a diffusion cell, such that drug dissolution and permeation across a Caco-2 monolayer would occur sequentially and simultaneously. The continuous system generally matched observed dissolution-absorption relationships from clinical studies. For example, the system successfully predicted the slow metoprolol and slow ranitidiine formulations to be permeation-rate-limited. The system predicted the slow piroxicam formulation to be dissolution-rate-limited, and the fast piroxicam formulation to be permeation-rate-limited, in spite of piroxicam's high permeability and low solubility. Additionally, the system indicated croscarmellose sodium enhanced ranitidine permeability and predicted solubilizing agents to not modulate permeability. These results suggest a dissolution/Caco-2 system to be an experimentally based tool that may predict dissolution-absorption relationships from oral solid dosage forms, and hence the relative contributions of dissolution and permeation to oral drug absorption kinetics.

  14. Drug release into hydrogel-based subcutaneous surrogates studied by UV imaging

    DEFF Research Database (Denmark)

    Ye, Fengbin; Larsen, Susan Weng; Yaghmur, Anan;

    2012-01-01

    of the performance of drug delivery systems based on in vitro experiments. The objective of this study was to evaluate a UV imaging-based method for real-time characterization of the release and transport of piroxicam in hydrogel-based subcutaneous tissue mimics/surrogates. Piroxicam partitioning from medium chain...... triglyceride (MCT) into 0.5% (w/v) agarose or 25% (w/v) F127-based hydrogels was investigated by monitoring the concentration profiles of the drug in the gels. The effect of pH on piroxicam distribution and diffusion coefficients was studied. For both hydrogel systems, the diffusion of piroxicam in the gels...... was not affected significantly by the pH change from 4.0 to 7.4 but a considerable change in the oil-gel distribution coefficients was found (24 and 34 times less at pH 7.4 as compared those observed at pH 4.0 for F127 and agarose gels, respectively). In addition, the release and transport processes of piroxicam...

  15. STABILITAS FISIKA DAN KIMIA REKRISTAL DAN DISPERSI PADAT PIROKSIKAM-PEG 6000

    Directory of Open Access Journals (Sweden)

    Annas Binarjo

    2015-05-01

    Full Text Available It is hoped that solid dispersion and recrystalization can solve the problem of low solubility of piroxicam. Metastable polymorph or amorph state can be formed in solid dispersion and recrystalization preparation, leading to a better dissolution. During storage, the metastable polymorph or amorph will be changed to stable crystal, so that the dissolution will be decreased (physical instability, beside that the increasing of solubility also trigger the higher rate of decomposition (chemical instability. This research was purposed to reveal these two instability. The research was began by preparing recrystal of piroxicam (R and solid dispersion piroxicam-PEG 6000 (DP by solvent method using aseton. These preparate were stored in room temperature (25oC. The dissolution was tested after 1, 2, 3, and 4 month of storage, using dissolution efficiency for 60 minutes (DE60 as parameter, and also the drug content in bulk preparate was determined. The result showed that recrystalization and solid dispersion preparation did not decrease the piroxicam content. During storage, the DE60 and piroxicam content in R and DP were not changed (p>0.05. It could be concluded that R and DP prepared had a stable dissolution and purity.

  16. Detection of Indomethacin and Piroxicam Added in Anti-rheumatism Chinese Patent Drugs%关于风湿类纯中成药中添加吲哚美辛和吡罗昔康检验方法的研究

    Institute of Scientific and Technical Information of China (English)

    张晓燕; 种宝贵

    2009-01-01

    目的:研究抗风湿类纯中成药添加吲哚美辛和吡罗昔康的检验方法.方法:采用高效液相色谱法对风湿关节炎片、风湿定胶囊等6种纯中成药制剂进行了模拟添加吲哚美辛和吡罗昔康的含量测定:色谱柱为迪马公司Cat.no.:99902 Ser.no.:8021405,流动相为磷酸缓冲液-乙腈(60:40);检测波长为254 nm,流速为1.0 mL·min-1.结果:6种纯中成药制剂均不含吲哚美辛和吡罗昔康.结论:本方法准确度高、分离度好、回收率高、专属性强.

  17. Effects of Micronization and Solid Dispersion Technologies on Oral Bioavailability of Piroxicam in Beagle Dogs%微粉化和固体分散体技术对吡罗昔康在Beagle犬体内口服生物利用度的影响

    Institute of Scientific and Technical Information of China (English)

    李模勇; 杨澄; 彭强

    2015-01-01

    为增加吡罗昔康(1)的溶出速度,采用气流粉碎法对1原药进行微粉化处理,或采用溶剂法以共聚维酮S630为载体制备固体分散体.将所得的微粉化药物和固体分散体分别制成片剂,并以市售1片为参比制剂,采用Beagle犬为模型进行药动学研究.结果表明,微粉化处理对1在Beagle犬体内的药动学行为无显著影响,但制备固体分散体能有效提高1的口服生物利用度.与参比制剂相比,采用微粉化1制备的片剂口服相对生物利用度为103.6%;当固体分散体片剂中1与共聚维酮S630质量比为1∶3和1∶5时,口服相对生物利用度为128.9%和138.9%.

  18. Determination of piroxicam illegally mixed into traditional Chinese medicine anti-rheumatism preparations by the liquid chromatography-quadrupole mass spectrometry method%液相色谱-质谱联用法测定中药抗风湿制剂中非法掺入吡罗昔康的研究

    Institute of Scientific and Technical Information of China (English)

    邱颖姮; 王铁杰; 杨敏; 李军

    2008-01-01

    目的:建立中药抗风湿制剂中非法掺入吡罗昔康专属性的检测方法.方法:采用液相色谱-串联四极杆质谱联用法.选用SunFireTM C18柱,以0.01 mol·L-1乙酸铵水溶液-乙腈(80:20)为流动相,检测波长334 am,流速为O.2 mL·min-1.对中药抗风湿制剂的提取液进行液相色谱-串联四极杆质谱分析.通过与对照品的色谱及质谱行为相比较,对中药抗风湿制剂中非法掺入的吡罗昔康进行定性鉴别.结果:在4种受试中药抗风湿制剂中,1种被检测到掺有吡罗昔康.结论:该方法选择性强,灵敏度高,可作为分析检测中药抗风湿制剂中非法掺入吡罗昔康的有效方法.

  19. Drug: D00127 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 0127.gif Anti-inflammatory Same as: C01608 Therapeutic category: 1149 2649 ATC code: M01AC01 M02AA07 S01BC06 cyclooxygenase...-1 (COX-1) inhibitor [HSA:5742] [KO:K00509]; cyclooxygenase-2 (COX-2) inhibitor [HSA:5743] [K...fication of drugs [BR:br08310] Enzymes Oxidoreductases cyclooxygenase-1 (COX-1) [HSA:5742] [KO:K00509] Pirox...icam [ATC:M01AC01 M02AA07 S01BC06] D00127 Piroxicam (JP16/USP/INN) cyclooxygenase

  20. Randomized comparison of effectiveness of unimodal opioid analgesia with multimodal analgesia in post–cesarean section pain management

    Directory of Open Access Journals (Sweden)

    Adeniji AO

    2013-05-01

    Full Text Available Adetunji Oladeni Adeniji,1 Oluseyi Olaboyede A Atanda21Department of Obstetrics and Gynaecology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria; 2Department of Obstetrics and Gynaecology, Ladoke Akintola University of Technology Teaching Hospital, Osogbo, NigeriaBackground: Postoperative pain leads to patient discomfort, decreased level of satisfaction, prolonged recovery, and higher health costs. Acute pain control therefore improves the overall quality of life in patients undergoing cesarean section. Pain relief is a fundamental human right, but there is no gold standard for post–cesarean section pain management.Objective: To compare the efficacy of pentazocine and tramadol used in unimodal and multimodal (in combination with piroxicam approach, in the management of post–cesarean section pain.Materials and methods: This study employed a random allocation design to compare the effectiveness of intramuscular pentazocine (60 mg or tramadol (100 mg as single analgesic agent and in combination with daily intramuscular piroxicam 20 mg, for the management of post–cesarean section pain during the immediate 12 hours after surgery. The primary outcome measure was control of postoperative pain, while the secondary outcome measures were the analgesic agent onset of action, duration of action, patient satisfaction, and maternal and neonatal adverse outcomes. Data obtained were entered into a predesigned sheet and analyzed with the Statistical Package for Social Sciences version 17. Means ± standard deviation (SD were calculated for the quantitative variables, and the difference between two independent groups was compared using unpaired Student's t-test. The level of significance was set at 0.05.Results: A total of 120 patients were equally and randomly allocated to four study groups – two that received unimodal analgesia (the pentazocine group and the tramadol group and two that received multimodal analgesia (the pentazocine-piroxicam

  1. The Myotoxic Effects of Microencapsulated Naproxen and Carrier Polymer After Intramuscular Injection in Rats

    Science.gov (United States)

    1996-10-10

    diclofenac, piroxicam, ketoprofen, metamizol magnesium, and ketorolac into skeletal muscle (hindlimb) of rats. All of the NSAIDs produced some degree... metamizol magnesium 400mglml. Unfortunately, this study did not assess for myotoxicity beyond 24 hours and therefore may have failed to observe an

  2. The effect of balanced analgesia on early convalescence after major orthopaedic surgery

    DEFF Research Database (Denmark)

    Møiniche, S; Hjortsø, N C; Hansen, B L

    1994-01-01

    Forty-two patients scheduled for total knee arthroplasty (n = 20) or hip arthroplasty (n = 22) were randomly allocated to receive either continuous epidural bupivacaine/morphine for 48 h postoperatively plus oral piroxicam, or general anaesthesia followed by a conventional intramuscular opioid an...

  3. Anti-inflammatory effects of eugenol nanoemulsion as a topical delivery system.

    Science.gov (United States)

    Esmaeili, Fariba; Rajabnejhad, Saeid; Partoazar, Ali Reza; Mehr, Shahram Ejtemaei; Faridi-Majidi, Reza; Sahebgharani, Mousa; Syedmoradi, Leila; Rajabnejhad, Mohammad Reza; Amani, Amir

    2016-11-01

    Eugenol is the main constituent of clove oil with anti-inflammatory properties. In this work, for the first time, O/W nanoemulsion of eugenol was designed for the evaluation of anti-inflammatory effects as a topical delivery system. Topical formulations containing 1%, 2% and 4% of eugenol as well as a nanoemulsion system containing 4% eugenol and 0.5% piroxicam were prepared. Further to physicochemical examinations, such as determination of particle size, polydispersity index, zeta potential and physical stability, anti-inflammatory activity was examined in carrageenan-induced paw edema in rats. The optimum formulation was found to contain 2% eugenol (oil phase), 14% Tween 20 (surfactant) and 14% isopropyl alcohol (co-surfactant) in water. Nanoemulsion with polydispersity index of 0.3 and median droplet diameter of 24.4 nm (d50) was obtained. Animal studies revealed that the nanoemulsions exhibited significantly improved anti-inflammatory activity after 1.5 h, compared with marketed piroxicam gel. Additionally, it was shown that increasing the concentration of eugenol did not show higher inhibition of inflammation. Also, the nanoemulsion having piroxicam showed less anti-inflammatory properties compared with the nanoemulsion without piroxicam.

  4. The effect of balanced analgesia on early convalescence after major orthopaedic surgery

    DEFF Research Database (Denmark)

    Møiniche, S; Hjortsø, N C; Hansen, B L;

    1994-01-01

    Forty-two patients scheduled for total knee arthroplasty (n = 20) or hip arthroplasty (n = 22) were randomly allocated to receive either continuous epidural bupivacaine/morphine for 48 h postoperatively plus oral piroxicam, or general anaesthesia followed by a conventional intramuscular opioid...

  5. Biocompatibility of Pectin-Protein Gels and Microencapsulates: In Vivo Study on Rats

    Science.gov (United States)

    Pectin-protein complex hydrogel beads were tested in vivo on rats. The beads were pre-loaded with a model drug, piroxicam (PX), in ethanol at different loading rates. The rats were starved 8 hr prior to experiment. The rats were then fed with the beads. Blood samples were taken in 2, 4, 6, 12, and 2...

  6. High-resolution gene expression profiling using RNA sequencing in patients with inflammatory bowel disease and in mouse models of colitis

    DEFF Research Database (Denmark)

    Holgersen, Kristine; Kutlu, Burak; Fox, Brian;

    2015-01-01

    pathways and assess the similarity between the experimental models and human disease. RNA sequencing was performed on colon biopsies from CD patients, UC patients and non-IBD controls. Genes shown to be significantly dysregulated in human IBD were used to study gene expression in colons from a piroxicam...

  7. IL-33 promotes GATA-3 polarization of gut-derived T cells in experimental and ulcerative colitis

    DEFF Research Database (Denmark)

    Seidelin, Jakob Benedict; Coskun, Mehmet; Kvist, Peter Helding;

    2015-01-01

    of the immune response in experimental colitis (piroxicam-accelerated colitis (PAC) in IL-10 -/- mice, dextran sodium sulfate (DSS) model) and UC.METHODS: Colonic IL-33 expression was determined in UC (8 active UC, 8 quiescent UC, and 7 controls) and experimental colitis. Mesenteric lymph node (MesLN) T cells...

  8. Prevention of postoperative pain by balanced analgesia

    DEFF Research Database (Denmark)

    Dahl, J B; Rosenberg, J; Dirkes, W E;

    1990-01-01

    Fourteen patients undergoing colorectal surgery received an intraoperative afferent neural block with combined intrathecal and extradural local anaesthetics plus a balanced postoperative low-dose regimen of extradural bupivacaine 10 mg h-1-morphine 0.2 mg h-1 and systemic piroxicam 20 mg/24 h...

  9. Characterics of exposure to non-steroid anti-inflammatory drugs in European databases.

    NARCIS (Netherlands)

    Vries, F. de; Kieler, H.; Dijk, L. van; Svensson, T.; Staa, T. van

    2010-01-01

    Background: A systematic review reported that users of naproxen, ibuprofen and piroxicam did not have an increased risk of myorcardial infarction (MI), whilst users of diclofenac and indomethacin showed significantly increased risk of MI (RRs 1.4 and 1.3). While there may be biological plausible exp

  10. Selective preparation of elusive and alternative single component polymorphic solid forms through multi-component crystallisation routes.

    Science.gov (United States)

    Thomas, Lynne H; Wales, Craig; Wilson, Chick C

    2016-05-31

    A transferable, simple, method for producing previously elusive and novel polymorphic forms of important active pharmaceutical ingredients (APIs; paracetamol (acetaminophen), piroxicam and piracetam) is demonstrated. Nitrogen heterocyclic co-molecules are employed to influence the self-assembly crystallisation process in a multi-component environment. Previously unknown solvates have also been synthesised by this method.

  11. Clinical outcome of partial cystectomy for transitional cell carcinoma of the canine bladder.

    Science.gov (United States)

    Marvel, S J; Séguin, B; Dailey, D D; Thamm, D H

    2017-02-20

    Canine transitional cell carcinoma (TCC) of the bladder has historically been treated with a combination of chemotherapy, cyclooxygenase inhibitors and radiation therapy. While surgery has been used to treat TCC of the bladder, its efficacy has yet to be established. Thirty-seven client owned dogs that underwent partial cystectomy +/- various nonsurgical treatments for TCC were retrospectively evaluated. The overall median progression-free interval (PFI) was 235 days and the median survival time (ST) was 348 days. Prognostic factors identified on univariate analysis significant for ST were age, tumor location, full thickness excision and frequency of piroxicam administration. Prognostic factors significant for PFI were full thickness excision and frequency of piroxicam administration. The median ST with partial cystectomy and daily piroxicam therapy, with or without chemotherapy, was 772 days. Dogs with non-trigonal bladder TCC treated with full thickness partial cystectomy and daily piroxicam (+/- chemotherapy) may have improved outcome compared to dogs treated with medical therapy. © 2017 John Wiley & Sons Ltd.

  12. Tumorigenesis in the multiple intestinal neoplasia mouse: redundancy of negative regulators and specificity of modifiers.

    Science.gov (United States)

    Halberg, R B; Katzung, D S; Hoff, P D; Moser, A R; Cole, C E; Lubet, R A; Donehower, L A; Jacoby, R F; Dove, W F

    2000-03-28

    The interaction between mutations in the tumor-suppressor genes Apc and p53 was studied in congenic mouse strains to minimize the influence of polymorphic modifiers. The multiplicity and invasiveness of intestinal adenomas of Apc(Min/+) (Min) mice was enhanced by deficiency for p53. In addition, the occurrence of desmoid fibromas was strongly enhanced by p53 deficiency. The genetic modifier Mom1 and the pharmacological agents piroxicam and difluoromethylornithine each reduced intestinal adenoma multiplicity in the absence of p53 function. Mom1 showed no influence on the development of desmoid fibromas, whereas the combination of piroxicam and difluoromethylornithine exerted a moderate effect. The ensemble of tumor suppressors and modifiers of a neoplastic process can be usefully analyzed in respect to tissue specificity and synergy.

  13. In vitro topical delivery of non-steroidal anti-inflammatory drugs through human skin.

    Science.gov (United States)

    Vincent, C M; Laugel, C; Marty, J P

    1999-06-01

    The objective of the present study was to evaluate in vitro the percutaneous absorption, across human skin, of 5 non-steroidal anti-inflammatory drugs (NSAIDs) formulated as gels: ketoprofen (CAS 22071-15-4), epolamine diclofenac (CAS 15307-86-5), piroxicam (CAS 36322-90-4) and niflumic acid (CAS 4394-00-7) or as emulgel: diclofenac sodium (CAS 15307-79-6) and to compare the different formulations as drug delivery systems. Because the concentrations of the NSAIDs in the different excipients were not identical, the comparison of their diffusional properties was expressed in term of release efficiency (or diffusion efficacy). The results obtained show that, across human skin under standardized experimental conditions, ketoprofen and piroxicam have the best rank order followed by niflumic acid, diclofenac sodium and epolamine diclofenac.

  14. Green synthesis and molecular recognition ability of patuletin coated gold nanoparticles.

    Science.gov (United States)

    Ateeq, Muhammad; Shah, Muhammad Raza; ul Ain, Noor; Bano, Samina; Anis, Itrat; Lubna; Faizi, Shaheen; Bertino, Massimo F; Sohaila Naz, Syeda

    2015-01-15

    Patuletin isolated from Tagetespatula was used as a capping and reducing agent to synthesize in one pot gold nanoparticles capped with patuletin. Conjugation of gold with patuletin was confirmed by FT-IR and UV-visible spectroscopy and amount of patuletin conjugated to gold nanoparticles was found to be 63.2% by weight. Particle sizes were measured by atomic force microscopy (AFM) and were found to have a mean diameter of about 45 nm. Patuletin-coated gold nanoparticles were found to be highly fluorescent. To examine their potential as chemical sensors, they were contacted with fourteen different drugs. Of these drugs, only one, piroxicam, was found to quench luminescence. Quenching obeyed Beer's law in a concentration range of 20-260 µM. Important for molecular recognition applications, fluorescence quenching by piroxicam was not affected by pH variation, elevated temperatures, addition of other drugs and addition of blood plasma to the colloidal suspensions.

  15. Tumorigenesis in the multiple intestinal neoplasia mouse: Redundancy of negative regulators and specificity of modifiers

    OpenAIRE

    Halberg, Richard B.; Katzung, Darren S.; Hoff, Peter D.; Moser, Amy R.; Cole, Carolyn E.; Lubet, Ronald A; Donehower, Lawrence A.; Jacoby, Russell F.; Dove, William F.

    2000-01-01

    The interaction between mutations in the tumor-suppressor genes Apc and p53 was studied in congenic mouse strains to minimize the influence of polymorphic modifiers. The multiplicity and invasiveness of intestinal adenomas of ApcMin/+ (Min) mice was enhanced by deficiency for p53. In addition, the occurrence of desmoid fibromas was strongly enhanced by p53 deficiency. The genetic modifier Mom1 and the pharmacological agents piroxicam and difluoromethylornithine each reduced intestinal adenoma...

  16. Screening and quantitative determination of twelve acidic and neutral pharmaceuticals in whole blood by liquid-liquid extraction and liquid chromatography-tandem mass spectrometry

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Steentoft, Anni; Buck, Maike

    2010-01-01

    . The method was fully validated for salicylic acid, paracetamol, phenobarbital, carisoprodol, meprobamate, topiramate, etodolac, chlorzoxazone, furosemide, ibuprofen, warfarin, and salicylamide. The method also tentatively includes thiopental, theophylline, piroxicam, naproxen, diclophenac, and modafinil......We describe a multi-method for simultaneous identification and quantification of 12 acidic and neutral compounds in whole blood. The method involves a simple liquid-liquid extraction, and the identification and quantification are performed using liquid chromatography-tandem mass spectrometry...

  17. Influence of Cyclodextrin Complexation with NSAIDs on NSAID/Cold Stress-Induced Gastric Ulceration in Rats

    Directory of Open Access Journals (Sweden)

    Ibrahim A. Alsarra, Mahrous O. Ahmed, Fars K. Alanazi, Kamal Eldin Hussein ElTahir, Abdulmalik M. Alsheikh, Steven H. Neau

    2010-01-01

    Full Text Available The aim of this work was to study the ability of β-cyclodextrin (β-CD or hydroxypropyl β-cyclodextrin (HP-β-CD to ameliorate the induction of gastric ulcers by a nonsteroidal anti-inflammatory drug, indomethacin or piroxicam, in rats exposed to restraint and hypothermic stress at 4 °C. Using oral gavage, rats fasted for 72 h were administered the equivalent of a 100 mg/kg dose of the assigned drug, alone or with the designated cyclodextrin (CD. The rats were placed in suitable rodent restrainers and then placed inside a ventilated refrigerator maintained at a temperature of 4 °C. Six hours later, each animal was removed, anaesthetized with ether, and the abdomen opened. Each stomach was removed, opened along the greater curvature and gently rinsed with isotonic saline solution. The induced gastric ulcers were examined and assessed with the help of a 10x binocular magnifier. Pronounced and marked gastric ulceration with complete loss of the mucosa, extensive deposition of fibrin and dense neutrophilic infiltrate were observed in rats treated with each of the drugs alone. Treatment with indomethacin or piroxicam alone induced ulcer indices of 26 ± 2.3 or 14 ± 1.8, respectively. However, β-CD and HP-β-CD each significantly suppressed ulceration due to restraint and cold stress. Rats treated with indomethacin or piroxicam in the presence of either β-CD or HP-β-CD exhibited normal tissues. Therefore, β-CD and HP-β-CD act as protective agents against gastrointestinal disorders produced by restraint and cold stress, even with the added stress from administration of either indomethacin or piroxicam.

  18. 吡罗昔康栓剂的制备及稳定性研究

    Institute of Scientific and Technical Information of China (English)

    谢晓慧; 宋菲; 张石革

    2001-01-01

    @@ 吡罗昔康(piroxicam)是昔康类非甾体抗炎药,其抗炎活性大于吲哚美辛、保泰松、布洛芬和阿司匹林等[1].为减轻此药的胃肠道不良反应,我们研制了吡罗昔康栓剂.

  19. Counterion effects on nano-confined metal–drug–DNA complexes

    Directory of Open Access Journals (Sweden)

    Nupur Biswas

    2016-01-01

    Full Text Available We have explored morphology of DNA molecules bound with Cu complexes of piroxicam (a non-steroidal anti-inflammatory drug molecules under one-dimensional confinement of thin films and have studied the effect of counterions present in a buffer. X-ray reflectivity at and away from the Cu K absorption edge and atomic force microscopy studies reveal that confinement segregates the drug molecules preferentially in a top layer of the DNA film, and counterions enhance this segregation.

  20. Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils

    Directory of Open Access Journals (Sweden)

    Paino I.M.M.

    2005-01-01

    Full Text Available The release of reactive oxygen specie (ROS by activated neutrophil is involved in both the antimicrobial and deleterious effects in chronic inflammation. The objective of the present investigation was to determine the effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs (NSAIDs on the production of ROS by stimulated rat neutrophils. Diclofenac (3.6 µM, indomethacin (12 µM, naproxen (160 µM, piroxicam (13 µM, and tenoxicam (30 µM were incubated at 37ºC in PBS (10 mM, pH 7.4, for 30 min with rat neutrophils (1 x 10(6 cells/ml stimulated by phorbol-12-myristate-13-acetate (100 nM. The ROS production was measured by luminol and lucigenin-dependent chemiluminescence. Except for naproxen, NSAIDs reduced ROS production: 58 ± 2% diclofenac, 90 ± 2% indomethacin, 33 ± 3% piroxicam, and 45 ± 6% tenoxicam (N = 6. For the lucigenin assay, naproxen, piroxicam and tenoxicam were ineffective. For indomethacin the inhibition was 52 ± 5% and diclofenac showed amplification in the light emission of 181 ± 60% (N = 6. Using the myeloperoxidase (MPO/H2O2/luminol system, the effects of NSAIDs on MPO activity were also screened. We found that NSAIDs inhibited both the peroxidation and chlorinating activity of MPO as follows: diclofenac (36 ± 10, 45 ± 3%, indomethacin (97 ± 2, 100 ± 1%, naproxen (56 ± 8, 76 ± 3%, piroxicam (77 ± 5, 99 ± 1%, and tenoxicam (90 ± 2, 100 ± 1%, respectively (N = 3. These results show that therapeutic levels of NSAIDs are able to suppress the oxygen-dependent antimicrobial or oxidative functions of neutrophils by inhibiting the generation of hypochlorous acid.

  1. Procédés d'oxydation avancée pour l’élimination d’anti-inflammatoires non-stéroïdiens résiduels présents en milieux aqueux

    OpenAIRE

    Feng, Ling

    2013-01-01

    The thesis mainly focused on the implementation of advanced oxidation processes for the elimination of three non-steroidal anti-inflammatory drugs-ketoprofen, naproxen and piroxicam in waters. The three compounds are among the most used medicines, whose presence in waters poses a potential ecotoxicological risk. Due to the low pharmaceuticals removal efficiency of traditional wastwater treatement plants, worldwide concerns and calls are raised for efficient and eco-friendly technologies. Adva...

  2. Effect of nonsteroidal anti-inflammatory drugs on glycogenolysis in isolated hepatocytes.

    OpenAIRE

    Brass, E. P.; Garrity, M. J.

    1985-01-01

    E-series prostaglandins have previously been demonstrated to inhibit hormone-stimulated glycogenolysis when added to isolated hepatocytes of the rat. In the present study, the effect of nonsteroidal anti-inflammatory drugs, which inhibit cyclo-oxygenase activity, on glycogenolysis was examined in the hepatocyte model. Ibuprofen (80 microM), indomethacin (50 microM) and meclofenamate (60 microM) all increased rates of glycogenolysis when added under basal conditions. In contrast, piroxicam (50...

  3. The Navy SEAL Physical Fitness Guide

    Science.gov (United States)

    1997-08-01

    for relieving muscle soreness than Ibuprofen - and Aspirin-based products. Table 12-2. Generic Names (and Common Names) for Various Non-Steroidal Anti...Ansaid) Piroxicam (Feldene, Antiflog) Ibuprofen (Advil, Motrin) Sulindac (Clinoril) Indomethacin (Indocin, Indocin SR) Tolmetin (Tolectin 200, Tolectin...Improved self-confidence Suppression of inhibitions230 Harmful Substances that Affect Performance T Ephedrine and Pseudoephedrine Ephedrine, and its

  4. 1,4-Dihydroxy-2-naphthoic acid from Propionibacterium freudenreichii reduces inflammation in interleukin-10-deficient mice with colitis by suppressing macrophage-derived proinflammatory cytokines.

    Science.gov (United States)

    Okada, Yoshikiyo; Tsuzuki, Yoshikazu; Narimatsu, Kazuyuki; Sato, Hirokazu; Ueda, Toshihide; Hozumi, Hideaki; Sato, Shingo; Hokari, Ryota; Kurihara, Chie; Komoto, Shunsuke; Watanabe, Chikako; Tomita, Kengo; Kawaguchi, Atsushi; Nagao, Shigeaki; Miura, Soichiro

    2013-09-01

    The anti-inflammatory mechanism of prebiotics has recently been shown to have an impact on the host immune system. DHNA from Propionibacterium freudenreichii is known to promote the proliferation of Bifidobacterium and can ameliorate colitis, although its mode of action remains unknown. In this study, we investigated whether DHNA attenuates inflammation in piroxicam-treated IL-10(-/-) mice, particularly focusing on the changes of the host immune mechanism. DHNA was administered to IL-10(-/-) mice with colitis, and the expression of adhesion molecules and mRNA levels of proinflammatory cytokines were determined. DHNA pretreatment attenuated the piroxicam-induced histological changes. The increased F4/80-positive cell infiltration and VCAM-1 expression were decreased by DHNA administration. The increased mRNA levels of proinflammatory cytokines were also suppressed by DHNA. In in vitro experiments, increased mRNA levels of proinflammatory cytokines after endotoxin exposure were decreased significantly by DHNA pretreatment in RAW264.7, a macrophage cell line, and IL-10(-/-) mice BMMs, whereas the expression of VCAM-1 in bEnd.3 cells, a endothelial cell line, was not affected. Taken together, these findings suggest that administration of DHNA is useful for the treatment of colitis in piroxicam-treated IL-10(-/-) mice and that attenuation of colitis by DHNA may partly be a result of its direct action on intestinal macrophages to inhibit proinflammatory cytokine production.

  5. Study of Osteoarthritis Treatment with Anti-Inflammatory Drugs: Cyclooxygenase-2 Inhibitor and Steroids

    Directory of Open Access Journals (Sweden)

    Hongsik Cho

    2015-01-01

    Full Text Available Patients with osteoarthritis (OA, a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs, and cyclooxygenase-2 (COX-2 selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM. To compare the effects of these treatments on chondrocyte metabolism, TNF-α was incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2. The chondrocytes were then treated with either a steroid (prednisone, a nonspecific COX inhibitor NSAID (piroxicam, or a COX-2 selective NSAID (celecoxib. Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxib in vivo was investigated using a posttraumatic OA (PTOA mouse model. In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 production in vitro and that celecoxib may demonstrate beneficial effects on anabolic metabolism in vivo.

  6. Rhizomes of Eremostachys laciniata: Isolation and Structure Elucidation of Chemical Constituents and a Clinical Trial on Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Abbas Delazar

    2013-08-01

    Full Text Available Purpose: The purpose of this study was the isolation and structure elucidation of chemical compounds from the rhizomes of Eremostachys laciniata (L Bunge (EL, an Iranian traditional medicinal herb with a thick root and pale purple or white flowers as well as the clinical studies on the therapeutic efficacy and safety of topical application of the EL extract in the management of some inflammatory conditions, e.g., arthritis, rheumatoid arthritis and septic arthritis (Riter’s syndrome. Methods: The structures of the isolated compounds were elucidated unequivocally on the basis of one and two dimensional NMR, UV and HR-FABMS spectroscopic data analyses. A single-blinded randomized clinical trial was carried out with the extract of the rhizomes of E. laciniata (EL to determine the efficacy and safety of the traditional uses of EL compared to that of piroxicam in treatment of inflammatory diseases, e.g., osteoarthritis, rheumatoid arthritis and Reiter’s syndrome. Results: Eleven iridoid glycosides, two phenylethanoids and two phytosterols were isolated and identified for the first time from the rhizomes of EL. After 14 days of treatment with the EL and piroxicam ointments, all groups showed significant improvements compared to the control groups. EL (5% ointment induced better initial therapeutic response than piroxicam (5% onitment. Conclusion: This clinical trial established that EL was suitable for topical applications as a safe and effective complementary therapy for inflammatory diseases.

  7. 针刺腰痛穴加外敷吡罗昔康治疗急性腰扭伤

    Institute of Scientific and Technical Information of China (English)

    张攀; 黄俊卿

    2014-01-01

    Objective To observe the acupuncture piroxicam patch YaoTong point and outward the clinical curative effect of treatment of acute lumbar sprain. Methods Choose 66 cases of patients with acute lumbar sprain, adopt acupuncture yaotong point method of treat-ment. Acupuncture treatment of pain after local topical piroxicam patch for three days. Results The clinical cure 52 cases, 14 cases were markedly effective, 0 no effect, the total effective rate was 100%. Conclusion Acupuncture yaotong point outward piroxicam patch has a good effect in treatment of acute lumbar sprain.%目的:观察针刺腰痛穴加外服吡罗昔康贴片治疗急性腰扭伤的临床疗效。方法选取急性腰扭伤患者66例,均采用针刺腰痛穴法治疗。针刺治疗后疼痛局部给予外敷吡罗昔康贴片3天。结果临床治愈52例,显效14例,无效0例,总有效率100%。结论针刺腰痛穴加外敷吡罗昔康贴片治疗急性腰扭伤疗效显著。

  8. Relationship between crystal structure and solid-state properties of pharmaceuticals

    Science.gov (United States)

    Sheth, Agam R.

    This thesis strives to understand the structure-property relationships of some pharmaceutical crystals at the molecular level with emphasis on the effect of secondary processing on the solid phase. Using single crystal X-ray diffractometry (SCXRD), the structure of warfarin sodium 2-propanol adduct (W) was established to be a true solvate, contrary to previous reports. Using dynamic water vapor sorption, optical and environmental scanning electron microscopy, SCXRD, powder X-ray diffractometry (PXRD), volume computations and molecular modeling, the effect of relative humidity and temperature on the crystal structure of W was investigated. Ab initio calculations on piroxicam showed that the difference in energy between the two polymorphs, I and II, arises predominantly from the difference between their lattice energies. The detailed hydrogen bonding networks of the two polymorphs are described and compared using graph sets. Despite stabilization of the polymorphs by hydrogen bonds, pair-wise distribution function transforms show a loss of polymorphic memory upon cryogrinding the two polymorphs, leading to a difference in recrystallization behavior between amorphous piroxicam prepared from polymorphs I and II. Structural and solid-state changes of piroxicam polymorphs under mechanical stress were investigated using cryogenic grinding, PXRD, diffuse-reflectance solid-state ultraviolet-visible spectroscopy, 13C solid-state nuclear magnetic resonance spectroscopy, and diffuse-reflectance solid-state Fourier-transform infrared spectroscopy. Intermolecular proton transfer was found to accompany changes in phase and color observed upon cryogrinding the two polymorphs. Model-free and model-fitting studies of the dehydration kinetics of piroxicam monohydrate (PM) showed the dependence of activation energy ( Ea) on both isothermal and non-isothermal heating conditions, and on the fraction of conversion. In the constant-E a region, isothermal dehydration follows the two

  9. Cyclooxygenase I and II inhibitors distinctly enhance hippocampal- and cortex-dependent cognitive functions in mice.

    Science.gov (United States)

    Syed, Huma; Ikram, Muhammad Faisal; Yaqinuddin, Ahmed; Ahmed, Touqeer

    2015-11-01

    Cyclooxygenase (COX) enzymes are expressed in the brain; however, their role in hippocampus-dependent and cortex-dependent cognitive functions remains to be fully elucidated. The aim of the present study was to comparatively investigate the effects of piroxicam, a selective COX-I inhibitor, and celecoxib, a selective COX‑II inhibitor, on cognitive functions in an AlCl3‑induced neurotoxicity mouse model to understand the specific role of each COX enzyme in the hippocampus and cortex. The AlCl3 (250 mg/kg) was administered to the mice in drinking water and the drugs were administered in feed for 30 days. Assessments of memory, including a Morris water maze, social behavior and nesting behavior were performed in control and treated mice. The RNA expression of the COX enzymes were analyzed using reverse transcription‑quantitative polymerase chain reaction analysis. An ex‑vivo 2,2‑Diphenyl‑1‑picrylhydrazyl assay was performed in the hippocampus and cortex. Following 30 days of treatment with thedrugs, the mice in the celecoxib‑ and piroxicam‑treated groups exhibited enhanced learning (6.84 ± 0.76 and 9.20 ± 1.08, respectively), compared with the AlCl3‑induced neurotoxicity group (21.14 ± 0.76) on the fifth day of the Morris water maze test. Celecoxib treatment improved social affiliation in the AlCl3‑induced neurotoxicity group, the results of which were superior to piroxicam. Piroxicam led to better improvement in nesting score in the AlCl3‑induced neurotoxicity group. Both drugs decreased the expression levels of COX‑I and COX‑II in the hippocampus and cortex, and rescued oxidative stress levels. These findings suggested that each drug distinctly affected cognitive functions, highlighting the distinctive roles of COX-I and COX-II in learning and memory.

  10. Pharmacokinetics of formulated tenoxicam transdermal delivery systems.

    Science.gov (United States)

    Kim, Taekyung; Kang, Eunyoung; Chun, Inkoo; Gwak, Hyesun

    2008-01-01

    To investigate the feasibility of developing a new tenoxicam transdermal delivery system (TDS), the pharmacokinetics of tenoxicam from various formulated TDS were evaluated and compared with values following oral administration of tenoxicam and with application of a piroxicam plaster (Trast) marketed in Korea. Based on previous in-vitro study results, a mixture of diethylene glycol monoethyl ether (DGME) and propylene glycol monolaurate (PGML) (40:60) was used as a vehicle, and caprylic acid, capric acid, lauric acid, oleic acid or linoleic acid (each at 3%) was added as an enhancer. Triethanolamine (5%) was used as a solubilizer, and Duro-Tak 87-2510 as a pressure-sensitive adhesive. Among these fatty acids used for the formulation of tenoxicam TDS, caprylic acid showed the greatest enhancing effect; the area under the plasma concentration-time profile (AUC) decreased in the order of caprylic acid>linoleic acid>or=oleic acid>lauric acid>capric acid. Compared with oral administration, maximum plasma concentration (Cmax) was significantly lower, and time to reach Cmax (Tmax) delayed with all formulated tenoxicam TDS. All formulated TDS resulted in a lower AUC than with the oral formulation, except for TDS containing caprylic acid, although the difference was statistically significant only with capric acid. The AUC for all the formulated tenoxicam TDS was significantly higher than that of the piroxicam plaster; TDS with caprylic acid increased AUC 8.53-fold compared with the piroxicam plaster. Even though the Tmax of tenoxicam TDS was not significantly different from that of the piroxicam plaster, Cmax was higher; formulations containing caprylic acid and linoleic acid increased Cmax by 7.39- and 8.76-fold, respectively. In conclusion, a formulation containing 1.5 mL DGME-PGML (40:60) with 3% caprylic acid and 5% triethanolamine mixed with 6 g Duro-Tak 87-2510 could be a good candidate for developing a new tenoxicam TDS to maintain a comparable extent of absorption

  11. A short history of anti-rheumatic therapy. III. Non steroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    P. Marson

    2011-06-01

    Full Text Available The chemical advances of the 20th century led to the synthesis of non steroidal anti-inflammatory drugs (NSAIDs, beginning from phenylbutazone and indomethacin and continuing with other new drugs, including ibuprofen, diclofenac, naproxen, piroxicam and, more recently, the highly selective COX-2 inhibitors (coxibs. This progress derived from the discovery of the mechanism of action of these drugs: the inhibition of synthesis of prostaglandins due to the cycloxigenase enzyme system, according to the experimental contributions of John R. Vane.

  12. pH dependence of drug-membrane interaction

    Science.gov (United States)

    Basak, Uttam Kumar; Datta, Alokmay

    2014-04-01

    Langmuir monolayer technique has been used to understand the interaction of piroxicam, a NSAID of oxicam class with the DMPC half membrane. It has been found that drug-membrane interaction is dependent on the pH of the environment. The interaction slightly increases with pH in the range 2.5-6.5 whereas the interaction becomes stronger in the pH range 6.6-8.5. The mechanism of interaction has been explained considering the pH dependent molecular conformation and ionic state of drug and lipid molecules.

  13. Drug induced `softening' in phospholipid monolayers

    Science.gov (United States)

    Basak, Uttam Kumar; Datta, Alokmay; Bhattacharya, Dhananjay

    2015-06-01

    Compressibility measurements on Langmuir monolayers of the phospholipid Dimystoryl Phospatidylcholine (DMPC) in pristine form and in the presence of the Non-steroidal Anti-inflammatory Drug (NSAID) Piroxicam at 0.025 drug/lipid (D/L) molecular ratio at different temperatures, show that the monolayer exhibits large increase (and subsequent decrease) in compressibility due to the drug in the vicinity of the Liquid Expanded - Liquid Condensed (LE-LC) phase transition. Molecular dynamics simulations of the lipid monolayer in presence of drug molecules show a disordering of the tail tilt, which is consistent with the above result.

  14. Drug: D01397 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available if Analgesia [DS:H00445 H00630] Therapeutic category: 1149 prodrug, active substance: Piroxicam [DR:D00127] cyclooxygenase...-1 (COX-1) inhibitor [HSA:5742] [KO:K00509]; cyclooxygenase-2 (COX-2) inhibitor [HSA:5743] [KO.../INN) Target-based classification of drugs [BR:br08310] Enzymes Oxidoreductases cyclooxygenase-1 (COX-1) [HS...A:5742] [KO:K00509] Ampiroxicam D01397 Ampiroxicam (JAN/INN) cyclooxygenase-2 (COX-2) [HSA:5743] [KO:K11987

  15. Modelado Molecular e Interacción Enzima-Ligando (Docking) de Antiinflamatorios Derivados de 4-Hidroxi 1,2-Benzotiazinas-3-Carboxamidas, 1,1-Dióxido Molecular Modelling and Docking Studies of Antiinflammatory Derivatives of 4-Hydroxi, 1,2-Benzothiazine 1,1-Dioxide

    OpenAIRE

    2009-01-01

    Este trabajo tiene como objetivo visualizar por métodos computacionales, el modo de interacción de los oxicanes con la ciclooxigenasa, lo que llevaría a proponer un mecanismo de acción a nivel molecular, hasta el momento desconocido y reconocer los grupos funcionales indispensables para la acción analgésica y antiinflamatoria. Se exploró el espacio conformacional y se efectuó la interacción enzima-ligando (docking) de meloxicam, piroxicam, lornoxicam, normeloxicam y 4`meloxicam, utilizando el...

  16. 吡罗昔康致肝功能损害1例报告

    Institute of Scientific and Technical Information of China (English)

    郑爱华

    2001-01-01

    @@ 吡罗昔康(Piroxicam)系苯噻嗪类的一种消炎、解热、镇痛药.其优点是用药剂量小,作用持续时间长.每日只服1次,每次20 mg,短期服用副作用少.临床上最常见的不良反应是胃肠道反应.引起肝功能损害较少见,本文病例报告如下.

  17. Solid-phase extraction-spectrophotometric determination of uranium(VI) in natural waters

    Energy Technology Data Exchange (ETDEWEB)

    Sadeghi, Susan; Mohammadzadeh, Darush [Department of Chemistry, University of Birjand, Birjand (Iran); Yamini, Yadollah [Department of Chemistry, Tarbiat Moddars University, Tehran (Iran)

    2003-03-01

    A method for the extraction and determination of uranyl ion in natural waters using octadecyl bonded silica membrane disks modified with piroxicam and spectrophotometry with arsenazo(III) is proposed. The perconcentration step was studied with regard to experimental parameters such as amount of extractant, type and amount of eluent, pH, flow rates and tolerance limit of diverse ions on the recovery of uranyl ion. The limit of detection of the proposed method is 0.4 {mu}g L{sup -1} of uranyl. The method was applied to the recovery of uranyl from different water samples. (orig.)

  18. Pharmacological treatment of actinic keratosis

    Directory of Open Access Journals (Sweden)

    Ewa Zwierzyńska

    2016-09-01

    Full Text Available Actinic keratosis (AK is a disease characterized by hyperkeratotic lesions on skin damaged by ultraviolet. radiation. These lesions may progress to squamous cell or basal cell carcinoma. Currently pharmacotherapy and different surgical procedures are used in AK therapy. The most common treatment options are 5-fluorouracil, imiquimod, diclofenac, ingenol mebutate, and first and third generation retinoids (retinol, adapalene, tazarotene. Furthermore, research is being carried out in order to test new medications including nicotinamide, resiquimod, piroxicam, potassium dobesilate and oleogel based on a triterpene extract (betulin, betulinic acid. Recently, the preventive effect of acetylsalicylic acid and celecoxib has also been investigated.

  19. INVESTIGATION OF DRUG RELEASE FROM BIODEGRADABLE PLG MICROSPHERES: EXPERIMENT AND THEORY

    Energy Technology Data Exchange (ETDEWEB)

    ANDREWS, MALCOLM J. [Los Alamos National Laboratory; BERCHANE, NADER S. [Los Alamos National Laboratory; CARSON, KENNETH H. [Los Alamos National Laboratory; RICE-FICHT, ALLISON C. [Los Alamos National Laboratory

    2007-01-30

    Piroxicam containing PLG microspheres having different size distributions were fabricated, and in vitro release kinetics were determined for each preparation. Based on the experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the system size was increased. The mathematical model gave a good fit to the experimental release data.

  20. Gastroprotective effect of zinc acexamate against damage induced by nonsteroidal antiinflammatory drugs. A morphological study.

    Science.gov (United States)

    Bulbena, O; Escolar, G; Navarro, C; Bravo, L; Pfeiffer, C J

    1993-04-01

    The gastroprotective effect of zinc acexamate against gastric damage induced by different nonsteroidal antiinflammatory drugs (indomethacin, diclofenac, and piroxicam) was morphologically assessed in the rat glandular stomach by light and scanning electron microscopy. In addition, the capability of these antiinflammatory drugs to inhibit gastric prostaglandin E2 production was compared with their ability to induce gastric lesions. Microscopically, disappearance of mucus glycoprotein and exfoliation of the mucosal surface were the most common findings. Surface ultrastructural lesions varied from minimal lesions of the surface epithelial cells to deep erosions of the gastric mucosa with release of associated cellular elements and sloughing of the denuded lamina propria. Diclofenac elicited the most powerful inhibitory activity on mucosal prostaglandin E2 (98% inhibition vs control), closely followed by piroxicam (97.8%) and indomethacin (91.05%). Pretreatment of animals with zinc acexamate significantly increased the presence of mucus glycoprotein, maintained the continuity of the surface epithelial cells, and decreased the depth of the mucosal erosions. The degree of protection exerted by zinc acexamate varied with the antiinflammatory, but was always evident.

  1. Systematic review of NSAID-induced adverse reactions in patients with rheumatoid arthritis in Japan.

    Science.gov (United States)

    Tomita, Tetsuya; Ochi, Takahiro; Sugano, Kentaro; Uemura, Shinichi; Makuch, Robert W

    2003-06-01

    Abstract A systematic review of randomized controlled clinical trials of nonsteroidal antiinflammatory drugs (NSAIDs) in rheumatoid arthritis (RA) patients was conducted to evaluate the risk of NSAID-induced adverse reactions. Double-blind, randomized, controlled trials with 6-week treatments for RA patients were included in the study. The endpoints for the analysis included any adverse reactions, digestive adverse reactions, and upper gastrointestinal (GI) adverse reactions. A fixed-effect model was used for estimation of the risk. Time-to-event analysis of the incidence of adverse reactions was also conducted. A total of 28 trials was included for the analysis, and a total of 30 NSAIDs were used in the trials. The proportion of patients who experienced any adverse reaction was as follows: piroxicam 18.9% (3 trials), diclofenac 18.8% (4 trials), indomethacin 22.1% (14 trials), and aspirin 25.0% (4 trials). The proportion of patients who experienced digestive adverse reactions was as follows: piroxicam 10.2%, diclofenac 10.6%, indomethacin 13.1%, and aspirin 14.1%. Most withdrawals due to adverse reaction occurred during the first 3 weeks after administration of the NSAID. Although the risk of NSAID-induced adverse reaction was different from drug to drug, the risk of adverse reaction was clinically significant.

  2. Gastro-protective effect of Crossopteryx febrifuga in Wistar rats.

    Science.gov (United States)

    Adeola, Salawu Oluwakanyinsola; Yahaya, Tijani Adeniyi; Hafsatu, Babayi; Chinwe, Nwaeze Angela; Maryjane, Ezeonu Chidimma; Sunday, Igwe; Adanna, Ndukuba Mary

    2011-01-01

    Preparations of Crossopteryx febrifuga (Afzel.) Benth. (Rubiaceae) are widely used in Northern Nigeria in the therapeutic management of trypanosomiasis, malaria and painful inflammatory disorders. Previous studies have shown that the methanolic stem bark extract of Crossopteryx febrifuga possesses significant analgesic and anti-inflammatory properties possibly mediated via Non-selective inhibition of cyclo-oxygenase pathways. In the present study, the methanolic stem bark extract of Crossopteryx febrifuga was evaluated against ethanol- and piroxicam-induced ulceration in rats. Histopathological studies of the rat stomach tissues were also carried out in order to determine its safety profile on the gastrointestinal tract (git). The extract (25, 50 and100 mg extract/kg body weight) significantly (P<0.05) and dose-dependently reduced ulcer index induced by ethanol (24 - 92%) and piroxicam (81.81- 98.60%). Histopathology of the rat stomach tissues from control and extract-treated groups at 25 mg/kg body weight extract showed mild inflammation characterized by infiltration of inflammatory cells, while the extract treated groups at 50 and 100mg/kg body weight and 200 mg misoprostol/kg body weight group showed no obvious lesions. These results showed that the extract had no deleterious effects and was cytoprotective on the gastrointestinal tract (git). It can thus be developed as a safe alternative to conventional non-steroidal anti-inflammatory drugs (NSAIDs) for the management of painful inflammatory disorders.

  3. Gelucire Based In Situ Gelling Emulsions: A Potential Carrier for Sustained Stomach Specific Delivery of Gastric Irritant Drugs

    Directory of Open Access Journals (Sweden)

    Ashwin Saxena

    2013-01-01

    Full Text Available Non steroidal anti-inflammatory drugs (NSAIDs are commonly prescribed medications to the geriatric patients for the treatment of arthritis and other painful disorders. The major side effects of NSAIDs are related to their effects on the stomach and bowels. The present study concerns assessment of the potential of liquid in situ gelling emulsion formulations (emulgels as patient compliant stomach specific sustained release carrier for the delivery of highly gastric irritant drug, Piroxicam. Emulgels were prepared, without using any emulgent, by mixing different concentrations of molten Gelucire 39/01 with low viscosity sodium alginate solution prepared in deionized water at 50°C. CaCO3 was used as buoyancy imparting as well as crosslinking agent. Emulgels so prepared were homogenous, physically stable, and rapidly formed into buoyant gelled mass when exposed to simulated gastric fluid (SGF, pH 1.2. Drug release studies carried out in SGF revealed significant retardation (P<0.05 of Piroxicam release from emulgels compared to conventional in situ gelling formulations prepared without Gelucire 39/01. Pharmacodynamic studies carried out in albino rats revealed significantly increased analgesic/anti-inflammatory response from in situ emulgels compared to conventional in situ gelling formulations. Further, in vivo toxicity studies carried out in albino rats revealed no signs of gastric ulceration upon prolonged dosing.

  4. Formulation,Optimization and Evaluation of Orally Disintegrating Tablet of Non-Steroidal Anti-inflammatory Drug

    Directory of Open Access Journals (Sweden)

    Patel Minal Arvindbhai

    2012-05-01

    Full Text Available Piroxicam is a non steroidal anti-inflammatory drug with analgesic properties. The purpose of this studywas to develop a taste masked orally disintegrating tablet of poorly soluble Piroxicam by directcompression technique with β-cyclodextrin (ß-CD complexes using various superdisintegrants likesodium starch glycolate, crospovidone XL and croscarmellose sodium. Complex was characterizedusing infrared spectroscopy, differential scanning calorimetry, % drug release study, gustatoryevaluation for taste masking. A 32 full factorial design was applied to systematically optimize the drugdisintegration time. The concentration of Crospovidone (X1 and concentration of Croscarmellose (X2were selected as independent variables. The Disintegration time (Y1 and Wetting time (Y2 wereselected as dependent variables. The prepared tablets were evaluated for hardness, friability,disintegration time, wetting time and In-vitro drug release. FT-IR studies and physical compatibilitystudy were conducted for drug, and drug excipient mixture for interactions if any. The differentformulations showed disintegration time between 12 to 58 sec. The results indicated that concentrationof Crospovidone (X1 and concentration of Croscarmellose (X2 significantly affected theDisintegration time (Y1 and Wetting time (Y2. Regression analysis and numerical optimization wereperformed to identify the best formulation. Formulation F10 prepared with croscarmellose (4.23% &crospovidone (6.74% was found to be the best formulation with disintegration time 16 sec, wetting time21 sec and % drug release in 10 min 94.23%.

  5. Antiinflammatory activity of tenoxicam gel on carrageenan-induced paw oedema in rats

    Directory of Open Access Journals (Sweden)

    Gupta G

    2006-01-01

    Full Text Available Tenoxicam is a nonsteroidal antiinflammatory drug, used in the treatment of inflammatory and degenerative disorders of the musculoskeletal system. It is from the oxicam group of nonsteroidal antiinflammatory agents. It is widely prescribed for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout, extra-articular disorders, bursitis, tendonitis, and nonarticular rheumatic condition. Tenoxicam has some side effects when taken orally, viz., epigastric pain, heartburn, nausea, diarrhoea, vomiting, peptic ulcer, and hepatic impairment. The aim of this study was to formulate topical gel containing 1% of tenoxicam in 1% carbopol-940 and PEG-4000 and to evaluate it for antiinflammatory activity using carrageenan-induced paw oedema in rats. The studies were conducted on Wistar rats of either sex (160-180 g. The change in oedema volume of the rat hind paw was measured using mercury plethysmometer. The readings were measured in terms of volume displaced in millimetre using a micropipette that has mark to 10 divisions in 1 ml. The carbopol gel formulation of tenoxicam containing 15% of ethanol and 5% of sodium lauryl sulphate was significantly more effective against oedema formation than the other formulation of tenoxicam gel and compared to the marketed product of piroxicam gel. Results suggest that the 1% tenoxicam gel in carbopol-940 inhibited 52% of carrageenan-induced oedema formation as compared with the 44% inhibition obtained with marketed product of piroxicam gel.

  6. Interactions Between Sirolimus and Anti-Inflammatory Drugs: Competitive Binding for Human Serum Albumin

    Science.gov (United States)

    Khodaei, Arash; Bolandnazar, Soheila; Valizadeh, Hadi; Hasani, Leila; Zakeri-Milani, Parvin

    2016-01-01

    Purpose: The aim of the present study was investigating the effects of three anti-inflammatory drugs, on Sirolimus protein biding. The binding site of Sirolimus on human serum albumin (HSA) was also determined. Methods: Six different concentrations of Sirolimus were separately exposed to HSA at pH 7.4 and 37°C. Ultrafiltration method was used for separating free drug; then free drug concentrations were measured by HPLC. Finally, Sirolimus protein binding parameters was calculated using Scatchard plots. The same processes were conducted in the presence of NSAIDs at lower concentration of albumin and different pH conditions. To characterize the binding site of Sirolimus on albumin, the free concentration of warfarin sodium and Diazepam, site I and II specific probes, bound to albumin were measured upon the addition of increasing Sirolimus concentrations. Results: Based on the obtained results presence of Diclofenac, Piroxicam and Naproxen, could significantly decrease the percentage of Sirolimus protein binding. The Binding reduction was the most in the presence of Piroxicam. Sirolimus-NSAIDs interactions were increased in higher pH values and also in lower albumin concentrations. Probe displacement study showed that Sirolimus may mainly bind to site I on albumin molecule. Conclusion: More considerations in co-administration of NSAIDs and Sirolimus is recommended. PMID:27478785

  7. Modulating drug release from gastric-floating microcapsules through spray-coating layers.

    Directory of Open Access Journals (Sweden)

    Wei Li Lee

    Full Text Available Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone (PCL coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose. The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system.

  8. MODULATION OF ANTI-INFLAMMATORY ACTIVITY OF NSAIDS IN NORMAL RATS TREATED WITH ANTIHISTAMINICS.

    Directory of Open Access Journals (Sweden)

    Nilam Nigam

    2012-10-01

    Full Text Available NSAIDs are frequently used for relief of inflammati on and Antihistaminics are indicated for simultaneous administration for aller gic manifestations. Opioids analgesics have been reported to interact with Antihistaminics. To e xplore the interacting potentiality, in the present study the effects of combined treatment with NSAIDs and antihistaminics were examined in rats. Anti-inflammatory effect was eval uated by Carrageenan induced hind paw oedema in rats. NSAIDs like aspirin, ibuprofen and pir oxicam were selected for study on per se and on concurrent administration with Antihistamini cs such as Promethazine, Cetrizine and Astemizole. All NSAIDs protected animals show anti-i nflammatory activity. Aspirin shows highly significant potentiation of anti-inflammatory effect at all dose level, however ibuprofen and piroxicam show highly significant anti-inflammatory effect at higher doses only and on concurrent administration of antihistaminics, aspiri n, piroxicam and ibuprofen with all antihistaminics produced highly significant potentiat ion except ibuprofen with Cetrizine produced significant potentiation of anti-inflammator y response at higher doses only.

  9. Role of PGE2 in the colonic motility: PGE2 generates and enhances spontaneous contractions of longitudinal smooth muscle in the rat colon.

    Science.gov (United States)

    Iizuka, Yumiko; Kuwahara, Atsukazu; Karaki, Shin-Ichiro

    2014-03-01

    The aim of this study was to determine which PGE2 receptors (EP1-4 receptors) influence colonic motility. Mucosa-free longitudinal smooth muscle strips of the rat middle colon spontaneously induced frequent phasic contractions (giant contractions, GCs) in vitro, and the GCs were almost completely abolished by a cyclooxygenase inhibitor, piroxicam, and by an EP3 receptor antagonist, ONO-AE3-240, but enhanced by tetrodotoxin (TTX). In the presence of piroxicam, exogenous PGE2, both ONO-AE-248 (EP3 agonist), and ONO-DI-004 (EP1 agonist) induced GC-like contractions, and increased the frequency and amplitude. These effects of EP receptor agonists were insensitive to TTX and ω-conotoxins. In immunohistochemistry, the EP1 and EP3 receptors were expressed in the longitudinal smooth muscle cells. These results suggest that the endogenous PGE2 spontaneously generates and enhances the frequent phasic contractions directly activating the EP1 and EP3 receptors expressed on longitudinal smooth muscle cells in the rat middle colon.

  10. Eicosanoids mediate nodulation reactions to bacterial Escherichia coli K 12 infections in larvae of the oriental blowfly,Chrysomya megacephala

    Institute of Scientific and Technical Information of China (English)

    Bing Chen; Yong Wang; Fen Zhu; Chao-Liang Lei

    2009-01-01

    Nodulation is the predominant cellular defense reaction to bacterial challenges in insects.In this study,third instar larvae of Chrysomya megacephala were injected with bacteria,Escherichia coli K 12 (10~6 CFU/mL,2μL),immediately prior to injection of inhibitors of eicosanoid biosynthesis,which sharply reduced nodulation response.Test larvae were treated with specific inhibitors of phospholipase A_2 (dexamethasone),cyclooxygenase (indomethacin,ibuprofen and piroxicam),dual cyclo-oxygenase/lipoxygenase (phenidone) and lipoxygenase (esculetin) and these reduced nodulation except esculetin.The influence of bacteria was obvious within 2 h of injection (5 nodules/larva),and increased to a maximum after 8 h (with 15 nodules/larva),and then significantly reduced over 24 h (9 nodules/larva).The inhibitory influence of dexamethasone was apparent within 2 h of injection (4 vs.5 nodules/larva),and nodulation was significantly reduced,compared to control,over 24 h (5 vs.8 nodules/larva).Increased dosages of ibuprofen,indomethacin,piroxicam and phenidone led to decreased numbers of nodules.Nodules continued to exist during the pupal stage.However,the effects of dexamethasone were reversed by treating bacteria-injected insects with an eicosanoid-precursor polyunsaturated fatty acid,arachidonic acid.These findings approved our view that eicosanoid can mediate cellular defense mechanisms in response to bacterial infections in another Dipteran insect C.megacephala.

  11. Supercritical CO₂ extract and essential oil of aerial part of Ledum palustre L.--Chemical composition and anti-inflammatory activity.

    Science.gov (United States)

    Baananou, Sameh; Bagdonaite, Edita; Marongiu, Bruno; Piras, Alessandra; Porcedda, Silvia; Falconieri, Danilo; Boughattas, Naceur A

    2015-01-01

    The anti-inflammatory activity of two extracts from the aerial parts of Ledum palustre has been reported. The volatile oil was obtained by supercritical fluid extraction (SFE) and the essential oil by hydrodistillation (HD). The oils were analysed by gas chromatography-mass spectrometry to monitor their composition. Both extracts shared as main compound (41.0-43.4%) ledol (23.3-26.7%) and ascaridole (15.1-4.5%). The anti-inflammatory activity was evaluated by the subcutaneous carrageenan injection-induced hind paw oedema. The treated animals received essential oil (SFE and HD), the reference group received ketoprofen or piroxicam and the control group received NaCl 0.9%. A statistical analysis was performed by the Student t-test. The results show that L. palustre essential oil enhanced a significant inhibition of oedema (50-73%) for HD oil and (52-80%) for SFE oil. These results were similar to those obtained with piroxicam (70%) and ketoprofen (55%).

  12. Analgesic-antiinflammatory drugs inhibit orbicularis oculi reflexes in humans via a central mode of action.

    Science.gov (United States)

    Ferracuti, S; Leardi, M G; Cruccu, G; Fabbri, A; Itil, T M

    1994-01-01

    1. A cross-over single blind study examined the possible central effects of non-opioid analgesic drugs on the trigeminal reflexes. 2. The corneal reflex and blink reflex (R1, R2) were recorded electromyographically and response areas measured in healthy volunteers before and after intramuscular injection of piroxicam (40 mg); and after intravenous injection of lysine acetylsalicylate (500 mg). After the last drug recording the subjects received intravenous naloxone (2 mg) followed 5 minutes later by further reflex testing. Saline was used as a placebo in control experiments. 3. Both analgesics reduced the corneal reflex: piroxicam induced a 27% and lysine acetylsalicylate a 21% a reduction that naloxone did not reverse. Neither drug reduced the early or the late component of the blink reflex. 4. The marked inhibitory changes that the two non-narcotic analgesics produced on the corneal reflex--a nociceptive response--indicate a centrally-mediated action. 5. Naloxone's failure to reverse the induced analgesia argues against opiate receptor mediation.

  13. Modulating drug release from gastric-floating microcapsules through spray-coating layers.

    Science.gov (United States)

    Lee, Wei Li; Tan, Jun Wei Melvin; Tan, Chaoyang Nicholas; Loo, Say Chye Joachim

    2014-01-01

    Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone) (PCL) coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose). The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system.

  14. Spectroscopic studies of the binding of Cu(II) complexes of oxicam NSAIDs to alternating G-C and homopolymeric G-C sequences.

    Science.gov (United States)

    Chakraborty, Sreeja; Bose, Madhuparna; Sarkar, Munna

    2014-03-25

    Drugs belonging to the Non-steroidal anti-inflammatory (NSAID) group are not only used as anti-inflammatory, analgesic and anti-pyretic agents, but also show anti-cancer effects. Complexing them with a bioactive metal like copper, show an enhancement in their anti-cancer effects compared to the bare drugs, whose exact mechanism of action is not yet fully understood. For the first time, it was shown by our group that Cu(II)-NSAIDs can directly bind to the DNA backbone. The ability of the copper complexes of NSAIDs namely meloxicam and piroxicam to bind to the DNA backbone could be a possible molecular mechanism behind their enhanced anticancer effects. Elucidating base sequence specific interaction of Cu(II)-NSAIDs to the DNA will provide information on their possible binding sites in the genome sequence. In this work, we present how these complexes respond to differences in structure and hydration pattern of GC rich sequences. For this, binding studies of Cu(II) complexes of piroxicam [Cu(II)-(Px)2 (L)2] and meloxicam [Cu(II)-(Mx)2 (L)] with alternating GC (polydG-dC) and homopolymeric GC (polydG-polydC) sequences were carried out using a combination of spectroscopic techniques that include UV-Vis absorption, fluorescence and circular dichroism (CD) spectroscopy. The Cu(II)-NSAIDs show strong binding affinity to both polydG-dC and polydG-polydC. The role reversal of Cu(II)-meloxicam from a strong binder of polydG-dC (Kb=11.5×10(3) M(-1)) to a weak binder of polydG-polydC (Kb=5.02×10(3) M(-1)), while Cu(II)-piroxicam changes from a strong binder of polydG-polydC (Kb=8.18×10(3) M(-1)) to a weak one of polydG-dC (Kb=2.18×10(3) M(-1)), point to the sensitivity of these complexes to changes in the backbone structures/hydration. Changes in the profiles of UV absorption band and CD difference spectra, upon complex binding to polynucleotides and the results of competitive binding assay using ethidium bromide (EtBr) fluorescence indicate different binding modes in each

  15. 液质联用法同时测定骨头帮胶囊中非法添加的4种化学成分%Simultaneous determination of four kinds of illegal chemicals added in Gutoubang capsule by HPLC-MS/MS

    Institute of Scientific and Technical Information of China (English)

    张建业; 李雨虹

    2012-01-01

    目的 采用液质联用法同时测定骨头帮胶囊中非法添加的吡罗昔康、醋酸泼尼松、双氯芬酸钠和布洛芬.方法 采用Kromasil C18色谱柱(250 mm×4.6 mm,5μm),流动相为乙腈-20 mmol·L-1乙酸铵溶液(0.1%乙酸)(43∶57),测定波长为330、240、280、220 nm,流速0.8 mL· min-1,柱温45℃.离子源为ESI源,正、负离子模式进行定性检测,采用HPLC法测定含量.结果 在HPLC - MS/MS中,受试制剂中分别检测出与吡罗昔康、醋酸泼尼松、双氯芬酸钠及布洛芬对照品一致的色谱峰、质谱峰.结论 所用方法选择性强、灵敏度好,结果准确可靠,可作为检测骨头帮胶囊中违禁添加吡罗昔康、醋酸泼尼松、双氯芬酸钠及布洛芬的有效方法.%OBJECTIVE To establish an LC - MS/MS method for simultaneous determination of piroxicam, prednisone acetate, diclofenac sodium and ibuprofen, which were illegally added to the Gutoubang capsules. METHODS A Kromasil C18 column was used (250 mm ×4.6 mm,5 μm) with the mobile phase of acetonitrile -20 mmol·L‐1 ammonium acetate(0. 1% acetic acid) (43 :51). The detective wavelengths were 330,240,280,220 nm. The flow rate was 0. 8 mL·min‐1 and the column temperature was 45 ℃. The content determination was based on high - performance liquid chromatography with electrospray ionization tandem mass ( HPLC - ESI -MS/MS) spectrometric detection in positive and negative ionization mode. RESULTS Piroxicam,prednisone acetate,diclofenac sodium and ibuprofen were found in the sample. CONCLUSION The method is selective, sensitive and suitable for the quantitative determination of illegal additives including piroxicam,prednisone acetate,diclofenac sodium and ibuprofen in the Gutoubang capsules.

  16. Spectroscopic studies of the binding of Cu(II) complexes of oxicam NSAIDs to alternating G-C and homopolymeric G-C sequences

    Science.gov (United States)

    Chakraborty, Sreeja; Bose, Madhuparna; Sarkar, Munna

    2014-03-01

    Drugs belonging to the Non-steroidal anti-inflammatory (NSAID) group are not only used as anti-inflammatory, analgesic and anti-pyretic agents, but also show anti-cancer effects. Complexing them with a bioactive metal like copper, show an enhancement in their anti-cancer effects compared to the bare drugs, whose exact mechanism of action is not yet fully understood. For the first time, it was shown by our group that Cu(II)-NSAIDs can directly bind to the DNA backbone. The ability of the copper complexes of NSAIDs namely meloxicam and piroxicam to bind to the DNA backbone could be a possible molecular mechanism behind their enhanced anticancer effects. Elucidating base sequence specific interaction of Cu(II)-NSAIDs to the DNA will provide information on their possible binding sites in the genome sequence. In this work, we present how these complexes respond to differences in structure and hydration pattern of GC rich sequences. For this, binding studies of Cu(II) complexes of piroxicam [Cu(II)-(Px)2 (L)2] and meloxicam [Cu(II)-(Mx)2 (L)] with alternating GC (polydG-dC) and homopolymeric GC (polydG-polydC) sequences were carried out using a combination of spectroscopic techniques that include UV-Vis absorption, fluorescence and circular dichroism (CD) spectroscopy. The Cu(II)-NSAIDs show strong binding affinity to both polydG-dC and polydG-polydC. The role reversal of Cu(II)-meloxicam from a strong binder of polydG-dC (Kb = 11.5 × 103 M-1) to a weak binder of polydG-polydC (Kb = 5.02 × 103 M-1), while Cu(II)-piroxicam changes from a strong binder of polydG-polydC (Kb = 8.18 × 103 M-1) to a weak one of polydG-dC (Kb = 2.18 × 103 M-1), point to the sensitivity of these complexes to changes in the backbone structures/hydration. Changes in the profiles of UV absorption band and CD difference spectra, upon complex binding to polynucleotides and the results of competitive binding assay using ethidium bromide (EtBr) fluorescence indicate different binding modes in each

  17. [Protection by zinc acexamate against gastric lesions induced by non-steroid anti-inflammatory agents].

    Science.gov (United States)

    Navarro, C; Bravo, L; Bulbena, O

    1993-03-01

    The ability of different non-steroidal anti-inflammatory drugs (diclofenac, indomethacin, ketoprofen, naproxen and piroxicam) to inhibit gastric prostaglandin E2 production in the rat was compared with their damaging potential on gastric mucosa. The influence of treatment with zinc acexamate (ZAC) on these two parameters was also determined. ZAC treatment significantly decreased the degree of gastric damage elicited by all the antiinflammatories tested. The experimental data confirm the complexity of the gastrolesive effect exerted by anti-inflammatory drugs and that only part of such effect would be related with their inhibition of prostaglandin synthesis. These results indicate that the gastroprotection of ZAC does not exclusively depend on the effect on the synthesis of prostaglandins by the gastric mucosa, yet it can additionally be exerted through alternative mechanisms.

  18. Measurement of the principal values of the chemical-shift tensors of overlapping protonated and unprotonated carbons with the 2D-SUPER technique and dipolar dephasing (DD-SUPER)

    Science.gov (United States)

    Liu, Wei; Wang, Wei D.; Wang, Wei; Bai, Shi; Dybowski, Cecil

    2010-09-01

    A modified 2D-SUPER technique is demonstrated to allow independent measurement of the principal values of the chemical-shift tensors of overlapping protonated and unprotonated carbons. The insertion of a dipolar-dephasing period into the sequence causes loss of signal from protonated carbons. The spectrum obtained with this modification allows one to determine the principal values of the unprotonated carbons with high precision. Subsequent fitting of the usual 2D-SUPER spectrum, with the chemical-shift parameters of the unprotonated carbons fixed, gives the parameters of the overlapped resonances of the protonated carbons. As an example, we report the determination of the 13C chemical-shift parameters of the carbons of form II of piroxicam. The experimental results are compared with those obtained from calculations using the DFT/GIAO method. Potential applications of this method are discussed.

  19. The effect of structural alterations of three mammalian serum albumins on their binding properties

    Science.gov (United States)

    Równicka-Zubik, J.; Sułkowski, L.; Maciążek-Jurczyk, M.; Sułkowska, A.

    2013-07-01

    The binding of piroxicam (PIR) to human (HSA), bovine (BSA) and sheep (SSA) serum albumin in native and destabilized/denaturated state was studied by the fluorescence quenching technique. Quenching of the intrinsic fluorescence of three analyzed serum albumins was observed due to selective exciting of tryptophanyl and tyrosil residues at 295 nm and 280 nm. Based on fluorescence emission spectra the quenching (KQ) and binding constants (Ka) were determined. The results showed that PIR is bound mainly in IIA subdomain of HSA and is additionally able to interact with tyrosil groups located in subdomains IB, IIB or IIIA. PIR interacts only with tryptophanyl residues of BSA and SSA [Trp-214, Trp-237 (IIA) and Trp-135, Trp-158 (IB)]. The presence of denaturating factors modified the mechanism of fluorescence quenching of SSA by PIR. Linear Scatchard plots suggest that HSA, BSA and SSA bind PIR in one class of binding sites.

  20. Anion-switchable supramolecular gels for controlling pharmaceutical crystal growth

    Science.gov (United States)

    Foster, Jonathan A.; Piepenbrock, Marc-Oliver M.; Lloyd, Gareth O.; Clarke, Nigel; Howard, Judith A. K.; Steed, Jonathan W.

    2010-12-01

    We describe the use of low-molecular-weight supramolecular gels as media for the growth of molecular crystals. Growth of a range of crystals of organic compounds, including pharmaceuticals, was achieved in bis(urea) gels. Low-molecular-weight supramolecular gelators allow access to an unlimited range of solvent systems, in contrast to conventional aqueous gels such as gelatin and agarose. A detailed study of carbamazepine crystal growth in four different bis(urea) gelators, including a metallogelator, is reported. The crystallization of a range of other drug substances, namely sparfloxacin, piroxicam, theophylline, caffeine, ibuprofen, acetaminophen (paracetamol), sulindac and indomethacin, was also achieved in supramolecular gel media without co-crystal formation. In many cases, crystals can be conveniently recovered from the gels by using supramolecular anion-triggered gel dissolution; however, crystals of substances that themselves bind to anions are dissolved by them. Overall, supramolecular gel-phase crystallization offers an extremely versatile new tool in pharmaceutical polymorph screening.

  1. Analysis of pharmaceutical creams: a useful approach based on solid-phase extraction (SPE) and UV spectrophotometry.

    Science.gov (United States)

    Bonazzi, D; Andrisano, V; Gatti, R; Cavrini, V

    1995-10-01

    Solid-phase extraction (SPE) using C-18, diol and ion-exchange sorbents followed by UV spectrophotometric (conventional and derivative mode) assay was applied to the analysis of basic, acidic and neutral drugs commercially available in creams. A representative set of drugs (promethazine, chlorhexidine, benzydamine, ketoprofen, ibuprofen, fentiazac, piroxicam, fluorouracil, crotamiton and hydrocortisone acetate) was selected, and for each drug the appropriate SPE conditions (adsorption, washing and elution) were investigated to obtain a practical and reliable sample clean-up. It was shown that the developed SPE procedures were capable of removing interfering cream components (excipients including preservatives) allowing accurate spectrophotometric analyses to be performed. In some applications, derivative spectrophotometry was advantageous over the conventional absorption mode with respect to higher selectivity and versatility.

  2. Isobolographic analysis of the antinociceptive interactions of clonidine with nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Miranda, H F; Pinardi, G

    2004-09-01

    The present study was undertaken to characterize the interactions between nonsteroidal anti-inflammatory drugs and the alpha(2)-adrenoceptor agonist clonidine in an acute nociceptive test. The writhing test was selected as a model of acute visceral pain. Isobolograms were constructed to assess the interactions of clonidine and each nonsteroidal anti-inflammatory drugs, when coadministered intraperitoneally and intrathecally (i.t.). The simultaneous intraperitoneal administration of fixed ratios of ED(50) fractions of all nonsteroidal anti-inflammatory drugs (naproxen, piroxicam, paracetamol, dipyrone or metamizol and nimesulide) combined with clonidine resulted in synergistic interactions. The same combinations administered intrathecally were additive. The synergistic interactions between systemic nonsteroidal anti-inflammatory drugs and clonidine may involve supraspinal mechanisms.

  3. HPLC测定吡罗昔康凝胶中吡罗昔康的含量

    Institute of Scientific and Technical Information of China (English)

    黄丽萍; 刘忠; 陈冠容; 王琳

    1999-01-01

    @@ 吡罗昔康(Piroxicam),又名炎痛喜康,为非甾体抗炎药,用于类风湿、风湿性关节炎和急性肌肉骨骼疾患等,包括腱鞘炎、肩周炎、扭伤、各种劳损和腰痛.由于吡罗昔康口服对胃肠道刺激较大,为克服此缺点,国内外研究者又陆续研制并上市了其胶囊、注射剂和缓释制剂.特别是透给药制剂备受推崇.吡罗昔康凝胶首先是由美国辉瑞公司(Pfizer)生产,商品名为Gel Feldene.

  4. On some toxinological aspects of the starfish Stellaster equestris (Retzius, 1805

    Directory of Open Access Journals (Sweden)

    U Kanagarajan

    2008-01-01

    Full Text Available Whole-body extracts in methanol were obtained from the starfish Stellaster equestris. The crude toxin was fractionated stepwise using diethylaminoethyl (DEAE cellulose column chromatography. The crude toxin was lethal to male albino mice at a dose of 1.00 mL (containing 531.0 µg/mL protein when injected intraperitoneally (IP but the toxicity was abolished in all cases except one upon fractionation. The crude toxin and all the adsorbed fractions exhibited potent hemolytic activity on chicken, goat and human blood. However, group B human erythrocytes were resistant to lysis by all fractions and group O by most of the fractions. Paw edema in mice was caused by the crude toxin and all fractions. Pheniramine maleate and piroxicam blocked the toxicity when administered earlier than, or along with, the crude or fractionated toxins but not when administered after the envenomation. Pretreatment with either of these drugs also blocked edema formation.

  5. STUDIES ON APPLICATION OF PROSOLVE AS A DIRECT COMPRESSIBLE VEHICLE FOR IMPROVING THE DISSOLUTION RATE OF POORLY SOLUBLE DRUGS

    Directory of Open Access Journals (Sweden)

    RAMANJI REDDY,RAVI, KRISHNA,PADMAVATHI,AJAY BABU

    2013-09-01

    Full Text Available Prosolve, a new directly compressible vehicle consists of microcrystalline cellulose (98% and colloidal silicon dioxide (2%. Piroxicam (20 mg tablets, celecoxib (100 mg tablets and aceclofenac (100 mg tablets were formulated employing prosolve and three super disintegrants namely pregelatinised starch, sodium starch glycolate and croscarmellose sodium by direct compression method with a view to enhance their dissolution rate. In the micromeritic evaluation microcrystalline cellulose and its blends with other tablet ingredients exhibited excellent to good flow needed for direct compression. All the tablets formulated employing prosolve fulfilled the Pharmacopoeial standards with regard to various tablet characters. These tablets also gave 2 to 5 fold increase in the dissolution rate when compared to commercial tablets. Among the three disintegrants sodium starch glycolate gave higher dissolution rates when compared with both pregelatinised starch and croscarmellose sodium.

  6. Método analítico para a determinação de meloxicam em plasma humano por cromatografia líquida de alta eficiência (CLAE Determination of meloxicam in human plasma by HPLC

    Directory of Open Access Journals (Sweden)

    Valentina Porta

    2005-06-01

    Full Text Available Desenvolveu-se e validou-se método analítico simples, rápido e específico para quantificação de meloxicam (inibidor da COX-2 em plasma humano através da cromatografia líquida de alta eficiência, para aplicação em estudos de bioequivalência. Piroxicam foi utilizado como padrão interno. Empregou-se cromatografia em fase reversa com coluna modelo Synergi RP-MAX (150 x 4,6 mm, à temperatura de 30 ºC e fase móvel constituída por mistura de acetonitrila e tampão fosfato 0,025 mol/L pH 4,5 (40:60, v/v, a um fluxo de 1,0 mL/min. Os analitos foram detectados por UV a 364 nm. As amostras de plasma foram acidificadas com ácido clorídrico 1 mol/L, extraídas utilizando-se éter terc-butil metílico e, após filtração e secagem, o resíduo foi reconstituído em 250 mL de fase móvel para injeção em CLAE. Os tempos de retenção para meloxicam (padrão e piroxicam (padrão interno foram 3,35 e 4,19 minutos, respectivamente. Este método apresentou linearidade na faixa de concentração entre 50-4000 ng/mL (R² = 0,9995, com limite de quantificação inferior de 50 ng/mL e exatidão de 114%. O método analítico desenvolvido neste trabalho demonstrou especificidade, linearidade, precisão e exatidão adequadas, permitindo sua aplicação em ensaios de bioequivalência.A simple, rapid and specific high-performance liquid cromatographic (HPLC method was developed and validated to estimate meloxicam (COX-2 inhibitor levels in human plasma. Piroxicam was used as internal standard. Reversed phase chromatography was conducted using a Synergi RP-MAX (150 x 4.6 mm column at 30 ºC and a mobile phase of acetonitrile and 0.025 mol/L pH 4,5 phosphate buffer (40:60, v/v, at a flow rate of 1mL/min. Analytes were detected at 364 nm. Plasma samples were acidified with 1 mol/L hydrochloric acid and extracted with tert-butyl methyl ether, evaporated to dryness, reconstituted in 250 mL of mobile phase and injected in the column. The retention time of

  7. Transdermal Iontophoresis of Non—steroid Anti—inflammatory Drugs

    Institute of Scientific and Technical Information of China (English)

    Jian-QigngGao; Wen-QuanLiang

    1997-01-01

    Oral admuinistration is currently the principal route for non-steroid anti-inflammatory drugs (NSAIDs).This type of drugs is highly effective in the treatment of rheumatoid arthritis.The clinical use of these drugs,howeever,is often limited because of their potential to cause some adverse reactions such as irritation and ulceration of the gastrointestinal mucosa,particularly at high dose levels.To minimize the side effects for patients,transdermal drug delivery should be a good way.In this project,iontophoresis has been used in conjunction with chemical penetriation enhancers to increase transdermal drug delivery.Piroxicam,indomethacin,naproxen and diclofenacsodium were employed to research into the effect and the mechanism of constant direct current iontophoresis and laurocapram pretreatment on the drug percutaneous fluxes.The synergisticeffect has also been discussed.Then diclofenac sodium gel has been prepared for investigating the feasibility of its clinical use.

  8. a Step Toward Development of Printable Dosage Forms for Poorly Soluble Drugs

    DEFF Research Database (Denmark)

    Raijada, Dhara; Genina, Natalja; Fors, Daniela

    2013-01-01

    printing (PIJ) and impression printing (flexography). The printed dosage forms were characterized using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and the amount of drug was determined using high-performance liquid chromatography. Solutions of PRX in polyethylene......The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkjet...... glycol 400 (PEG-400):ethanol (40:60) and in PEG-400 were found to be optimal formulations for PIJ and flexography, respectively. SEM-EDX analysis revealed no visible solid particles on the printed dosage forms indicating the drug most likely remained in solution after printing. More accurate drug...

  9. A novel gammaherpesvirus found in oral squamous cell carcinomas in sun bears (Helarctos malayanus).

    Science.gov (United States)

    Lam, Lydia; Garner, Michael M; Miller, Christine L; Milne, Victoria E; Cook, Kimberly A; Riggs, Gary; Grillo, James F; Childress, April L; Wellehan, James F X

    2013-01-01

    A novel herpesvirus was detected in sun bears (Helarctos malayanus) with oral squamous cell carcinoma. Five captive sun bears from 4 institutions in the United States presented with oral lesions ranging from erythema and mild erosions to nodular, ulcerated masses. All 5 were diagnosed with squamous cell carcinoma. The tumors were treated with surgical resection but recurrence, local extension, or appearance of new lesions was noted in all cases. Intralesional chemotherapy was administered in 2 cases, and the nonsteroidal anti-inflammatory drug piroxicam was administered in 3 cases. Virus was detected in 4 of the 5 bears' tissue samples using a consensus herpesvirus polymerase chain reaction. Nucleotide sequencing and phylogenetic analysis showed that this herpesvirus is in the subfamily Gammaherpesvirinae and distinct from other known herpesviruses. The association between the herpesvirus and squamous cell carcinoma is unknown. The current study presents a novel gammaherpesvirus within the order Ursidae, with the name Ursid herpesvirus 1 proposed.

  10. The effect of balanced analgesia on early convalescence after major orthopaedic surgery

    DEFF Research Database (Denmark)

    Møiniche, S; Hjortsø, N C; Hansen, B L;

    1994-01-01

    Forty-two patients scheduled for total knee arthroplasty (n = 20) or hip arthroplasty (n = 22) were randomly allocated to receive either continuous epidural bupivacaine/morphine for 48 h postoperatively plus oral piroxicam, or general anaesthesia followed by a conventional intramuscular opioid...... and acetaminophen regimen. Patients undergoing knee- or hip arthroplasty treated with epidural analgesia had significantly lower pain scores during mobilization under the 48 h epidural infusion compared with patients receiving conventional treatment, while no important differences were observed after cessation...... of the epidural regimen. However, the achieved pain relief had no impact on postoperative convalescence parameters, such as ambulation, patient activity including need for nursing care, fatigue or hospital stay. Late postoperative pain, fatigue and conservative attitudes and routines in the postoperative care...

  11. Deviation from van't Hoff dependence in RP-LC induced by tautomeric interconversion observed for four compounds.

    Science.gov (United States)

    Galaon, Toma; David, Victor

    2011-06-01

    The most encountered situations in reversed-phase liquid chromatography for temperature dependence of retention are those obeying the linear equation known as the van't Hoff plot. When studying compounds that are involved in structural modifications, it is likely that the temperature dependences of their retention factors do not follow this rule. It is the aim of this paper to report some particular cases when compounds involved in tautomeric interconversion have a different retention behavior with temperature: a deviation from the linearity of ln k on 1/T, or, in certain temperature ranges, temperature increase leading to a retention increase. Examples of compounds exhibiting deviation from the van't Hoff temperature dependence are piroxicam, drotaverine, vincamine, and epivincamine. A simple thermodynamic model relying on tautomeric equilibria in mobile phase is proposed for these compounds, which gives a polynomial dependence between ln k and 1/T.

  12. Cutaneous reactions to analgesic-antipyretics and nonsteroidal anti-inflammatory drugs. Analysis of reports to the spontaneous reporting system of the Gruppo Italiano Studi Epidemiologici in Dermatologia.

    Science.gov (United States)

    1993-01-01

    We analyzed the cutaneous reactions to systemic analgesic-antipyretics and non-steroidal anti-inflammatory drugs reported to the spontaneous reporting system of the Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED). The system has been active since 1988, with periodic intensive surveillance exercises, and 202 dermatologists have collaborated. Up to December 1991, 2,137 reactions had been collected, of which 713 were reactions to systemic analgesic-antipyretics and nonsteroidal anti-inflammatory drugs. A general profile of the reactions was identifiable. It included, in order of frequency, urticaria/angioedema, fixed eruptions, exanthemas, erythema multiforme and Stevens Johnson syndrome. Fixed eruptions and Stevens Johnson syndrome were reported with exceedingly high frequency in association with feprazone. Our system also revealed previously unreported reactions, including fixed eruption to nimesulide, fixed eruption to piroxicam and fixed eruption to flurbiprofen.

  13. a Step Toward Development of Printable Dosage Forms for Poorly Soluble Drugs

    DEFF Research Database (Denmark)

    Raijada, Dhara; Genina, Natalja; Fors, Daniela

    2013-01-01

    printing (PIJ) and impression printing (flexography). The printed dosage forms were characterized using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and the amount of drug was determined using high-performance liquid chromatography. Solutions of PRX in polyethylene......The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkjet...... glycol 400 (PEG-400):ethanol (40:60) and in PEG-400 were found to be optimal formulations for PIJ and flexography, respectively. SEM-EDX analysis revealed no visible solid particles on the printed dosage forms indicating the drug most likely remained in solution after printing. More accurate drug...

  14. NSAID-sensitive antihistamine-induced urticaria/angioedema.

    Science.gov (United States)

    Cimbollek, S; Ortega Camarero, M; Avila, R; Quiralte, J; Prados, M

    2011-01-01

    We present a case of urticaria caused by antihistamines in a patient with nonsteroidal anti-inflammatory drug (NSAID) sensitivity. A 35-year-old man experienced, on 2 separate occasions, immediate generalized urticaria during treatment with ibuprofen and naproxen, respectively. A single-blind, placebo-controlled oral challenge (SBPCOC) with piroxicam was carried out, and resulted in urticaria and angioedema 3 hours later. Two hours after initial clinical resolution, the patient developed multiple wheals on the trunk and upper limbs. He described similar delayed reactions after oral antihistamine administration on previous occasions. SBPCOCs with acetaminophen and etoricoxib were performed, with good tolerance. Skin prick and patch tests with loratadine and cetirizine were negative. After an SBPCOC with loratadine, the patient developed generalized urticaria 90 minutes after intake. Tolerance to fexofenadine 180 mg was confirmed. We describe the first case of a possible new subset of antihistamine urticaria, and suggest calling this NSAID-sensitive antihistamine-induced urticaria/angioedema.

  15. Monitoring of multiple solid-state transformations at tablet surfaces using multi-series near-infrared hyperspectral imaging and multivariate curve resolution

    DEFF Research Database (Denmark)

    Alexandrino, Guilherme L; Khorasani, Milad Rouhi; Amigo Rubio, Jose Manuel

    2015-01-01

    -state transformations. The preprocessed spectra from the images (dataset) were arranged in augmented matrices, according to the composition of the tablets, and the profile of the overlapped compounds (relative concentration) along the solid-state transformations in the pixels was resolved by using multivariate curve......The assessment of the solid-state stability of active pharmaceutical ingredient (API) and/or excipients in solid dosage forms during manufacturing and storage is mandatory for safeguarding quality of the final products. In this work, the solid-state transformations in tablets prepared as blends...... of piroxicam monohydrate (API), polyvinylpyrrolidone and the lactose forms monohydrate or anhydrate were studied when the tablets were exposed to the 23-120°C range. Multi-series near-infrared hyperspectral images were obtained from the surface of each sample for unveiling the local evolution of the solid...

  16. Synthesis, spectroscopic and DFT structural characterization of two novel ruthenium(III) oxicam complexes. In vivo evaluation of anti-inflammatory and gastric damaging activities.

    Science.gov (United States)

    Tamasi, Gabriella; Bernini, Caterina; Corbini, Gianfranco; Owens, Natalie F; Messori, Luigi; Scaletti, Federica; Massai, Lara; Giudice, Pietro Lo; Cini, Renzo

    2014-05-01

    The reactions of ruthenium(III) chloride trihydrate with piroxicam (H2PIR) and tenoxicam (H2TEN), two widely used non-steroidal anti-inflammatory drugs, afforded [Ru(III)Cl2(H2PIR)(HPIR)],·1, and [Ru(III)Cl2(H2TEN)(HTEN)],·2. Both compounds were obtained as pure green solids through purification via flash column chromatography. Characterizations were accomplished through UV-vis and IR spectroscopy, potentiometry and HPLC. Quantum mechanics and density functional computational methods were applied to investigate their respective molecular structures. The experimental and computational results are in agreement with a pseudo-octahedral coordination where the two chlorido ligands are in trans positions (apical) and the two trans-N,O chelating oxicam ligands occupy the equatorial sites. Both compounds revealed an acceptable solubility and stability profile upon dissolution in a standard buffer at physiological pH. Nonetheless, the addition of biologically occurring reducing agents caused spectral changes. The two complexes manifested a poor reactivity with the model proteins cytochrome c and lysozyme: no evidence for adduct formation was indeed obtained based on a standard ESI MS analysis; in contrast, some significant reactivity with serum albumin was proved spectrophotometrically. Remarkably, both study compounds revealed pronounced anti-edema effects in vivo suggesting that the pharmacological actions of the ligands are mostly retained; in addition, they were less irritating than piroxicam on the gastric mucosa when the coordination compounds and free oxicam were administered at the same overall molar concentration of the ligand. Overall, the present results point out that ruthenium coordination may represent an effective strategy to improve the pharmacological properties of oxicam drugs reducing their undesired side effects.

  17. A simple, rapid and sensitive RP-HPLC-UV method for the simultaneous determination of sorafenib & paclitaxel in plasma and pharmaceutical dosage forms: Application to pharmacokinetic study.

    Science.gov (United States)

    Khan, Ismail; Iqbal, Zafar; Khan, Abad; Hassan, Muhammad; Nasir, Fazle; Raza, Abida; Ahmad, Lateef; Khan, Amjad; Akhlaq Mughal, Muhammad

    2016-10-15

    A simple, economical, fast, and sensitive RP-HPLC-UV method has been developed for the simultaneous quantification of Sorafenib and paclitaxel in biological samples and formulations using piroxicam as an internal standard. The experimental conditions were optimized and method was validated according to the standard guidelines. The separation of both the analytes and internal standard was achieved on Discovery HS C18 column (250mm×4.6mm, 5μm) using Acetonitrile and TFA (0.025%) in the ratio of (65:35V/V) as the mobile phase in isocratic mode at a flow rate of 1ml/min, with a wavelength of 245nm and at a column oven temperature of 25°Cin a short run time of 12min. The limits of detection (LLOD) were 5 and 10ng/ml while the limits of quantification (LLOQ) were 10 and 15ng/ml for sorafenib and paclitaxel, respectively. Sorafenib, paclitaxel and piroxicam (IS) were extracted from biological samples by applying acetonitrile as a precipitating and extraction solvent. The method is linear in the range of 15-20,000ng/ml for paclitaxel and 10-5000ng/ml for sorafenib, respectively. The method is sensitive and reliable by considering both of its intra-day and inter-day co-efficient of variance. The method was successfully applied for the quantification of the above mentioned drugs in plasma. The developed method will be applied towards sorafenib and paclitaxel pharmacokinetics studies in animal models.

  18. DESIGN AND EVALUATION OF LOW COST DIRECTLY COMPRESSIBLE EXCIPIENTS - II

    Directory of Open Access Journals (Sweden)

    Swamy P. V.

    2010-12-01

    Full Text Available The aim of the present study was to develop dispersible / mouth dissolving tablets (orodispersible tablets using piroxicam as a model drug for improving patient compliance, employing low cost directly compressible co-processed granular excipients developed in our laboratory, based on various sugars/polyols such as mannitol, maltodextrin and dicalcium phosphate dihydrate along with a native food grade corn starch. The designed tablet formulations were evaluated for hardness, friability, weight variation, in vitro dispersion time, wetting time, water absorption ratio, drug content, in-vitro dissolution rate (in pH 6.8 phosphate buffer, short-term stability and drug-excipient interaction (IR spectroscopy. Among the designed piroxicam tablets, one formulation prepared with the granular excipient containing 25% w/w corn starch and 75% w/w dicalcium phosphate dihydrate using starch paste for granulation, without super disintegrant addition was found to be promising dispersible tablet formulation (in vitro dispersion time of 17.66 s and wetting time 8.4 s. Another tablet formulation prepared with the granular excipient containing mannitol and food grade corn starch (50:50 ratio and granulated with starch paste, along with 2% w/w crospovidone as superdisintegrant emerged as promising orodispersible tablet formulation (in vitro dispersion time 17.66 s and wetting time 14.3 s. Short-term stability studies of promising formulations (over a period of 3 months indicated that there are no significant changes in drug content and in vitro dispersion time (p<0.05. IR-spectroscopic studies indicated that there are no drug–excipient interactions.

  19. Development of micro-fibrous solid dispersions of poorly water-soluble drugs in sucrose using temperature-controlled centrifugal spinning

    Science.gov (United States)

    Marano, Stefania; Barker, Susan Anne; Raimi-Abraham, Bahijja Tolulope; Missaghi, Shahrzad; Rajabi-Siahboomi, Ali; Craig, Duncan Q.M.

    2016-01-01

    Solid dispersion technology represents a successful approach to addressing the bioavailability issues caused by the low aqueous solubility of many Biopharmaceutics Classification System (BCS) Class II drugs. In this study, the use of high-yield manufacture of fiber-based dispersion is explored as an alternative approach to monolith production methods. A temperature-controlled solvent-free centrifugal spinning process was used to produce sucrose-based microfibers containing the poorly water-soluble drugs olanzapine and piroxicam (both BCS Class II); these were successfully incorporated into the microfibers and the basic characteristics of fiber diameter, glassy behavior, drug loading capacity and drug–sucrose interaction assessment were measured. Scanning electron microscopy revealed that bead-free drug-loaded microfibers with homogenous morphology and diameter in the range of a few micrometers were prepared using our process. Differential scanning calorimetric and X-ray diffraction analyses showed that both drug and carrier were present in the amorphous state in the microfibers, although in the case of piroxicam-loaded microfibers, the presence of small amounts of crystalline drug was observed under polarized light microscopy and in Fourier transform infrared spectra. Drug dissolution performance was evaluated under both sink and non-sink conditions and was found to be significantly enhanced compared to the corresponding crystalline physical mixtures and pure drugs, with evidence of supersaturation behavior noted under non-sink conditions. This study has demonstrated that microfiber-based dispersions may be manufactured by the centrifugal spinning process and may possess characteristics that are favorable for the enhanced dissolution and oral absorption of drugs. PMID:27012901

  20. New Synthesis, Structure and Analgesic Properties of Methyl 1-R-4-Methyl-2,2-Dioxo-1H-2λ6,1-Benzothiazine-3-Carboxylates

    Directory of Open Access Journals (Sweden)

    Liliana Azotla-Cruz

    2017-01-01

    Full Text Available According to the principles of the methodology of bioisosteric replacements a series of methyl 1-R-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates has been obtained as potential analgesics. In addition, a fundamentally new strategy for the synthesis of compounds of this chemical class involving the introduction of N-alkyl substituent at the final stage in 2,1-benzothiazine nucleus already formed has been proposed. Using nuclear magnetic resonance (NMR spectroscopy, mass spectrometry and X-ray diffraction analysis it has been proven that in the DMSO/K2CO3 system the reaction of methyl 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylate and alkyl halides leads to formation of N-substituted derivatives with good yields regardless of the structure of the alkylating agent. The peculiarities of NMR (1Н and 13С spectra of the compounds synthesized, their mass spectrometric behavior and the spatial structure are discussed. In N-benzyl derivative the ability to form a monosolvate with methanol has been found. According to the results of the pharmacological testing conducted on the model of the thermal tail-flick it has been determined that replacement of 4-ОН-group in methyl 1-R-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates for the methyl group is actually bioisosteric since all methyl 1-R-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates synthesized demonstrated a statistically significant analgesic effect. The majority of the substances can inhibit the thermal pain response much more effective than piroxicam in the same dose. Under the same conditions as an analgesic the N-methyl-substituted analog exceeds not only piroxicam, but more active meloxicam as well. Therefore, it deserves in-depth biological studies on other experimental models.

  1. 大叶碎米荠胶囊治疗腰肌劳损76例临床观察%Clinical observation on Cardamine Macrophylla Willd.Capsule in the treatment of 76 patients with lumbar muscle strain

    Institute of Scientific and Technical Information of China (English)

    周凯; 李东辉; 刘江舟; 周效思

    2011-01-01

    Objective: To study curative effect of Cardamine Macrophylla Willd. Capsule in the treatment of lumbar muscle strain. Methods: 147 patients who met the full diagnostic criteria were divided into treatment group (76 cases) and control group (71 cases). The treatment group were treated with Cardamine Macrophylla Willd. Capsule per os, while the control group were treated with Western medicine Piroxicam Tablets per os. The comprehensive curative effects of the two groups were summarized after 15 days. Results: The total effective rate of the treatment group was 93.42%, and that of the control group was 74.65%, the curative effect was found to be better in the treatment group than that in the control group (P<0.05). Conclusion: The curative effect in the treatment group treated with Cardamine Macrophylla Willd. Capsule (per os) was significantly better than that in the control group treated with Piroxicam Tablets (per os).%目的:观察大叶碎米荠(Cardamine macrophylla Willd.)治疗腰肌劳损的临床疗效.方法:将我院符合诊断标准的腰肌劳损147例患者分为治疗组(76例)和对照组(71例),治疗组以口服大叶碎米荠胶囊治疗,对照组予口服吡罗昔康治疗.15 d后对两组综合疗效进行比较.结果:治疗组总有效率为93.42%,对照组为74.65%,两组总有效率比较差异有统计学意义(P<0.05).结论:口服大叶碎米荠治疗腰肌劳损的疗效明显,优于吡罗昔康对照组.

  2. Association of individual non-steroidal anti-inflammatory drugs and chronic kidney disease: a population-based case control study.

    Directory of Open Access Journals (Sweden)

    Ylenia Ingrasciotta

    Full Text Available Non-steroidal anti-inflammatory agents (NSAIDs are known to be associated with renal damage. No clear evidence exists regarding differential risk of chronic kidney disease (CKD, specifically, across various NSAIDs.The aim of this population-based case-control study was to evaluate the association between use of individual NSAIDs and risk of CKD in a general population of Southern Italy.A nested case-control study was carried out using the general practice Arianna database, identifying incident CKD patients as cases and matched controls from 2006 to 2011. The date of first CKD diagnosis was defined as the index date (ID. Conditional logistic regressions were performed to estimate the risk of CKD associated with NSAIDs by class and individual drugs as compared to non-use during different time windows (within one year, six or three months prior to ID, with the latter being defined as current users. Among current users, the effect of cumulative exposure to these drugs was evaluated.Overall, 1,989 CKD cases and 7,906 matched controls were identified. A statistically significant increase in the risk of CKD was found for current users of oxicams (adjusted OR: 1.68; 95% CI: 1.15-2.44 and concerning individual compounds, for ketorolac (adj. OR: 2.54; 95% CI: 1.45-4.44, meloxicam (adj. OR: 1.98; 95% CI: 1.01-3.87 and piroxicam (adj. OR: 1.95; 95% CI: 1.19-3.21.The risk of CKD varies across individual NSAIDs. Increased risk has been found for ketorolac, which may precipitate subclinical CKD through acute renal damage, and long-term exposure to oxicams, especially meloxicam and piroxicam.

  3. Development of micro-fibrous solid dispersions of poorly water-soluble drugs in sucrose using temperature-controlled centrifugal spinning.

    Science.gov (United States)

    Marano, Stefania; Barker, Susan Anne; Raimi-Abraham, Bahijja Tolulope; Missaghi, Shahrzad; Rajabi-Siahboomi, Ali; Craig, Duncan Q M

    2016-06-01

    Solid dispersion technology represents a successful approach to addressing the bioavailability issues caused by the low aqueous solubility of many Biopharmaceutics Classification System (BCS) Class II drugs. In this study, the use of high-yield manufacture of fiber-based dispersion is explored as an alternative approach to monolith production methods. A temperature-controlled solvent-free centrifugal spinning process was used to produce sucrose-based microfibers containing the poorly water-soluble drugs olanzapine and piroxicam (both BCS Class II); these were successfully incorporated into the microfibers and the basic characteristics of fiber diameter, glassy behavior, drug loading capacity and drug-sucrose interaction assessment were measured. Scanning electron microscopy revealed that bead-free drug-loaded microfibers with homogenous morphology and diameter in the range of a few micrometers were prepared using our process. Differential scanning calorimetric and X-ray diffraction analyses showed that both drug and carrier were present in the amorphous state in the microfibers, although in the case of piroxicam-loaded microfibers, the presence of small amounts of crystalline drug was observed under polarized light microscopy and in Fourier transform infrared spectra. Drug dissolution performance was evaluated under both sink and non-sink conditions and was found to be significantly enhanced compared to the corresponding crystalline physical mixtures and pure drugs, with evidence of supersaturation behavior noted under non-sink conditions. This study has demonstrated that microfiber-based dispersions may be manufactured by the centrifugal spinning process and may possess characteristics that are favorable for the enhanced dissolution and oral absorption of drugs.

  4. Calcarea carbonica derivative complex (M8 as adjuvant treatment of inflammatory mammary carcinoma in a dog

    Directory of Open Access Journals (Sweden)

    Simone Domit Guérios

    2011-09-01

    Full Text Available Background: Inflammatory mammary carcinoma (IMC is locally aggressive, fast growing, highly malignant tumor that affects humans and dogs. Affected dogs usually are presented with generalized edema, pain, erythema, and skin ulceration in mammary glands. Surgery is not recommended and an effective treatment has not been established [1]. Calcarea carbonica derivative complex (M8 has demonstrated anticancer properties in a murine model, by improving innate immune response against tumor cells [2,3]. M8 is a complex high diluted medication comprised of a 10%-20% concentration of Calcarea carbonica, Aconitum napellus, Arsenicum album, Asa foetida, Conium maculatum, Ipecacuanha, Phosphorus, Rhus tox, Silicea, Sulphur, and Thuya occidentalis, all in decimal dilutions of Hahnemann in distilled water and submitted to vigorous shaking. Aim: Describe an association of M8 and piroxicam (Non-steroidal anti-inflammatory drug to treat a dog with IMC. Discussion: A 7 years old, mixed breed intact female dog was presented to the Federal University of Parana - Veterinary Hospital, Curitiba (HV-UFPR for mammary glands examination. The owners related inflammation of mammary glands with clinical course of approximately 10 days, which was treated for mastitis (cephalexin and metergoline without clinical improvement. Clinical examination revealed erythema, increased skin warmth, pain on palpation, and plaque involving the 4th and 5th right mammary glands. Abdominal ultrasound and serum biochemistry were unremarkable. Thoracic radiographs showed suspicious images of pulmonary metastasis. Fine needle biopsy was taken for cytologic examination. Cytological interpretation was a malignant epithelial neoplasm, probably a mammary carcinoma. Diagnosis of IMC was based on clinical signs and cytopathology. Dog was treated with oral (0.5 mL and topical M8 twice a day for 15 days, and pyroxican, 0.3mg/kg, PO, q24h. Clinical improvement was observed 7 days after starting

  5. Reconstrução de ponte nasal com tela de titânio após exérese tumoral em um cão Nasal bridge reconstruction with titanium mesh after tumor excision in a dog

    Directory of Open Access Journals (Sweden)

    Renan Marcel Krüger

    2011-03-01

    Full Text Available O presente trabalho relata o uso de tela de titânio como alternativa para reconstrução do defeito ósseo criado pela ressecção agressiva de carcinoma de células escamosas da ponte nasal em cão. Após o tratamento quimioterápico com 5-fluorouracil tópico e sistêmico associado à piroxicam para a redução da massa tumoral, foi realizada a ressecção cirúrgica da região comprometida e reparo do defeito ósseo com tela de titânio e posterior recobrimento com retalho músculo-cutâneo unipediculado de avanço. A principal complicação no período pós-operatório foi a formação de enfisema subcutâneo, controlado em três dias com drenagem do ar e aplicação de bandagens compressivas. O animal permaneceu sem sinais de recidiva por oito meses. No décimo mês pós-operatório, o paciente apresentou miíase no local da recidiva e a proprietária optou pela eutanásia. Com esse caso, foi possível concluir que a tela de titânio foi um material adequado para a reconstrução da ponte nasal, tendo como principal complicação a ocorrência de enfisema subcutâneo.This paper describes the use of titanium mesh as an alternative for reconstruction of bone defect created by resection of aggressive squamous cell carcinoma of the nasal bridge in a dog. After chemotherapy with topic and systemic 5-fluorouracil associated with piroxicam for the tumor mass reduction, it was performed a surgical resection of the affected region, repair of bone defects with titanium mesh and subsequent closing of the wound with musculocutaneous single pedicle advancement flap. The main complication in the postoperative period was the formation of subcutaneous emphysema, which was controlled in three days with air drainage and application of compression bandages. The animal remained without signs of recurrence for eight months. In the tenth month postoperatively, the patient presented myiasis in local recurrence and the owner opted for euthanasia. In this case, it

  6. Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage

    Institute of Scientific and Technical Information of China (English)

    Corrado Blandizzi; Matteo Fornai; Rocchina Colucci; Gianfranco Natale; Valter Lubrano; Cristina Vassalle; Luca Antonioli; Gloria Lazzeri; Mario Del Tacca

    2005-01-01

    AIM: This study investigated the mechanisms of protection afforded by the proton pump inhibitor lansoprazole against gastric injury induced by different non-steroidal antiinflammatory drugs (NSAIDs) in rats.METHODS: Male Sprague-Dawley rats were orally treated with indomethacin (100 μmol/kg), diclofenac (60 μmol/kg),piroxicam (150 μmol/kg) or ketoprofen (150 μmol/kg).Thirty minutes before NSAIDs, animals were orally treated with lansoprazole 18 or 90 μmol/kg. Four hours after the end of treatments, the following parameters were assessed: gastric mucosal PGE2, malondialdehyde (MDA), myeloperoxidase (MPO) or non-proteic sulfhydryl compounds (GSH) levels; reverse transcription-polymerase chain reaction (RT-PCR) of mucosal COX-2 mRNA; gastric acid secretion in pylorus-ligated animals; in vitro effects of lansoprazole (1-300 μmol/L) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate.RESULTS: All NSAIDs elicited mucosal necrotic lesions which were associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels were detected in the gastric mucosa of indomethacin- or piroxicam-treated animals. Indomethacin enhanced mucosal cyclooxygenase-2 expression, while not affecting cyclooxygenase-1. At the oral dose of 18 μmol/kg lansoprazole partly counteracted diclofenac-induced mucosal damage, whereas at 90 μmol/kg it markedly prevented injuries evoked by all test NSAIDs. Lansoprazole at 90 μmol/kg reversed also the effects of NSAIDs on MPO, MDA and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced cyclooxygenase-2 expression. However, both lansoprazole doses markedly inhibited acid secretion in pylorus-ligated rats. Lansoprazole concentration-dependently reduced the oxidation of LDLs in vitro.CONCLUSION: These results suggest that, besides the inhibition of acid secretion, lansoprazole protection against NSAID

  7. Prevention of nephrotoxicity of ochratoxin A, a food contaminant.

    Science.gov (United States)

    Creppy, E E; Baudrimont, I; Betbeder, A M

    1995-12-01

    Ochratoxin A (OTA) is a mycotoxin produced by ubiquitous Aspergilli, mainly by Aspergillus ochraceus and also by Penicilium verrucosum. It was found all over the world in feed and human food and blood as well as in animal blood and tissues. The most threatening effects of OTA are its nephrotoxicity and carcinogenicity, since this mycotoxin is nephrotoxic to all animal species studied so far and is increasingly involved in the Balkan endemic nephropathy (BEN), a human chronic interstitial nephropathy which is most of the time associated to urinary tract tumours. Since it seems impossible to avoid contamination of foodstuffs by toxigenic fungi, detoxification and detoxication for OTA are needed. To reduce or abolish the OTA-induced toxic effects, several mechanisms were investigated. The results of these investigations showed that some of the potential antidotes were efficient in preventing the main OTA toxic effects whereas some others were not. Promising compounds are structural analogues of OTA, and/or compounds having a high binding affinity for plasma proteins such as piroxicam, a non-steroidal anti-inflammatory drug (NSAID). Some enzymes such as superoxide dismutase (SOD) and catalase, radical scavengers, vitamins, prostaglandin (PG) synthesis inhibitors, (such as piroxicam), pH modificators, adsorbant resin such as cholestyramine etc. are efficient in vivo. Some of the results obtained in vivo were already confirmed in vitro and gave useful information on how to safely use these antidotes. The most generally acting compound seems to be A19 (Aspartame), a structural analogue of OTA and phenylalanine. When given to rats A19 (25 mg/kg/48 h) combined to OTA (289 micrograms/kg/48 h) for several weeks largely prevented OTA nephrotoxicity and genotoxicity. When given after intoxication of animals with OTA it washes out the toxin efficiently from the body. In vitro, A19 (10 micrograms/ml) prevents OTA (20-500 micrograms/ml) binding to plasma proteins. Its general

  8. Simultaneous determination of 12 pharmaceuticals in water samples by ultrasound-assisted dispersive liquid-liquid microextraction coupled with ultra-high performance liquid chromatography with tandem mass spectrometry.

    Science.gov (United States)

    Guan, Jin; Zhang, Chi; Wang, Yang; Guo, Yiguang; Huang, Peiting; Zhao, Longshan

    2016-11-01

    A new analytical method was developed for simultaneous determination of 12 pharmaceuticals using ultrasound-assisted dispersive liquid-liquid microextraction (DLLME) followed by ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS). Six nonsteroidal anti-inflammatory drugs (NSAIDs, ketoprofen, mefenamic acid, tolfenamic acid, naproxen, sulindac, and piroxicam) and six antibiotics (tinidazole, cefuroxime axetil, ciprofloxacin, sulfamethoxazole, sulfadiazine, and chloramphenicol) were extracted by ultrasound-assisted DLLME using dichloromethane (800 μL) and methanol/acetonitrile (1:1, v/v, 1200 μL) as the extraction and dispersive solvents, respectively. The factors affecting the extraction efficiency, such as the type and volume of extraction and dispersive solvent, vortex and ultrasonic time, sample pH, and ionic strength, were optimized. The ultrasound-assisted process was applied to accelerate the formation of the fine cloudy solution by using a small volume of dispersive solvent, which increased the extraction efficiency and reduced the equilibrium time. Under the optimal conditions, the calibration curves showed good linearity in the range of 0.04-20 ng mL(-1) (ciprofloxacin and sulfadiazine), 0.2-100 ng mL(-1) (ketoprofen, tinidazole, cefuroxime axetil, naproxen, sulfamethoxazole, and sulindac), and 1-200 ng mL(-1) (mefenamic acid, tolfenamic acid, piroxicam, and chloramphenicol). The LODs and LOQs of the method were in the range of 0.006-0.091 and 0.018-0.281 ng mL(-1), respectively. The relative recoveries of the target analytes were in the range from 76.77 to 99.97 % with RSDs between 1.6 and 8.8 %. The developed method was successfully applied to the extraction and analysis of 12 pharmaceuticals in five kinds of water samples (drinking water, running water, river water, influent and effluent wastewater) with satisfactory results. Graphical Abstract Twelve pharmaceuticals in water samples analyted by UHPLC

  9. Determination of non-opioid analgesics in adulterated food and dietary supplements by LC-MS/MS.

    Science.gov (United States)

    Kim, Hyung Joo; Lee, Ji Hyun; Park, Hyoung Joon; Kim, Jung-Yeon; Cho, Sooyeul; Kim, Woo Seong

    2014-01-01

    Commercially available non-opioid analgesics such as acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) have been used to adulterate some foods and dietary supplements. Considering the rapid growth of the dietary supplement market, it is essential to analyse various analgesics used for adulteration over a time period. Acetaminophen and 16 NSAIDs used to adulterate food and dietary supplements were simultaneously determined by LC-MS/MS. The method was validated by determining the coefficient of determinations, limit of quantification and recovery, and samples were analysed for the determination of analgesics. Consequently, acetaminophen, diclofenac, ibuprofen, indomethacin, naproxen and piroxicam were detected in 53 samples (n = 214). Ibuprofen was the most commonly used adulterant, which was detected in a wide concentration range (1.06-233.40 mg g(-1)) and was present in about one-third of the adulterated samples. Various types of samples, in particular pills and capsules (73.6% of the total positive samples), were found to be adulterated with non-opioid analgesics. Samples containing high concentrations of analgesics can have a deleterious effect on human health, and thus the continued monitoring of adulterated food and dietary supplements is essential to maintain a healthy life.

  10. Fast RPLC-UV method on short sub-two microns particles packed column for the assay of tenoxicam in plasma samples.

    Science.gov (United States)

    Sora, Iulia; Galaon, Toma; Udrescu, Stefan; Negru, Jean; David, Victor; Medvedovici, Andrei

    2007-03-12

    An extraction-less sample preparation technique followed by a RPLC-UV method on sub-two microns particles packed short column were used for the assay of tenoxicam in plasma samples. Protein precipitation was made by means of trichloroacetic acid addition. Supernatant was injected to the chromatographic column without any further pH adjustment. The mobile phase consisted in a mixture of acetonitrile and aqueous 0.1% phosphoric acid, at 2 mL/min flow rate and gradient elution. The Zorbax SB-C18 column (50 mm length, 4.6 mm internal diameter and 1.8 microm particle size) was thermostated at 60 degrees C. The mobile phase gradient composition program allowed separation of tenoxicam and piroxicam (internal standard), column clean-up and re-equilibration within 4 min. UV detection was achieved at 368+/-10 nm. The method is characterized by a low limit of quantitation of 25 ng/mL for tenoxicam, with a linearity interval up to 5500 ng/mL. The use of a low volume detection cell and detector high frequency data acquisition rate produced high precision and accuracy through a whole bioequivalence study of tenoxicam in two commercially available tablet formulations, after a single oral administration dose. Full method validation is presented. The high throughput characteristic of the proposed method allowed full validation and bioanalytical study completion within a 96 h period.

  11. In vitro percutaneous absorption of tenoxicam from pressure-sensitive adhesive matrices across the hairless mouse skin.

    Science.gov (United States)

    Gwak, H S; Chun, I K

    2001-12-01

    To investigate the feasibility of developing a new tenoxicam plaster, the effects of vehicles and penetration enhancers on the in vitro permeation of tenoxicam from a pressure-sensitive adhesive (PSA) matrices across the dorsal hairless mouse skin were studied. Vehicles employed in this study were propylene glycol (PG)-oleyl alcohol (OAI), PG-oleic acid (OA), and diethylene glycol monoethyl ether (DGME)-propylene glycol monolaurate (PGML) cosolvents with/without fatty acids. In this study, amines such as triethanolamine (TEA) and tromethamine (TM) were additionally used as a solubilizer. Among PSAs used, Duro-Tak 87-2510 showed much higher release rate than either Duro-Tak 87-2100 or Duro-Tak 87-2196. The relatively high flux rate was obtained with the formulation of DGME-PGML (40:60, v/v) with 3% OA and 5% TM, and the flux increased as a function of the dose; the initial flux up to 12 h was 4.98 +/- 1.38 microg/cm2/h at the tenoxicam dose of 50 mg/70 cm2. This flux was much higher than that of a commercial piroxicam patch (Trast) (1.24 +/- 0.73 microg/ cm2/hr) with almost only one-third that of the commercial patch. Therefore, these observations indicated that these composition of tenoxicam plaster may be practically applicable.

  12. Preparation, structural analysis, and properties of tenoxicam cocrystals.

    Science.gov (United States)

    Patel, Jagdishwar R; Carlton, Robert A; Needham, Thomas E; Chichester, Clinton O; Vogt, Frederick G

    2012-10-15

    Cocrystals of tenoxicam, a non-steroidal anti-inflammatory drug, are screened, prepared, and characterized in this study. Nine tenoxicam cocrystals were identified using solvent-drop grinding (SDG) techniques. Structural characterization was performed using powder X-ray diffraction (PXRD), differential scanning calorimetry, and multinuclear solid-state NMR (SSNMR). Thermal analysis, PXRD, and 1D SSNMR are used to detect solvates and phase mixtures encountered in SDG cocrystal screening. 2D SSNMR methods are then used to confirm cocrystal formation and determine structural aspects for selected cocrystals formed with saccharin, salicylic acid, succinic acid, and glycolic acid in comparison to Forms I and III of tenoxicam. Molecular association is demonstrated using cross-polarization heteronuclear dipolar correlation (CP-HETCOR) methods involving (1)H and (13)C nuclei. Short-range (1)H-(13)C CP-HETCOR and (1)H-(1)H double-quantum interactions between atoms of interest, including those engaged in hydrogen bonding, are used to reveal local aspects of the cocrystal structure. (15)N SSNMR is used to assess ionization state and the potential for zwitterionization in the selected cocrystals. The tenoxicam saccharin cocrystal was found to be similar in structure to a previously-reported cocrystal of piroxicam and saccharin. The four selected cocrystals yielded intrinsic dissolution rates that were similar or reduced relative to tenoxicam Form III.

  13. Gastrotoxic activity and inhibitory effects on gastric mucosal PGE2 production with different non-steroidal anti-inflammatory drugs: modifications induced by pretreatment with zinc acexamate.

    Science.gov (United States)

    Navarro, C; Bravo, M L; Carulla, C; Bulbena, O

    1994-06-01

    Gastrotoxic activities of different non-steroidal anti-inflammatory drugs (NSAIDs) (diclofenac, indomethacin, ketoprofen, naproxen and piroxicam) administered per os were compared with their ability to inhibit gastric prostaglandin E2 (PGE2) synthesis in the rat. In a parallel study, effects of pretreatment with zinc acexamate (ZAC) were also assessed. NSAIDs invariably caused gastric mucosal damage and a decrease of PGE2 levels. A good correlation between the decrease of PGE2 levels and the index of gastric lesion (r = 0.41; p < 0.021) was observed when results obtained with the different NSAIDs were pooled. ZAC pretreatment significantly decreased the overall severity of lesions induced by NSAIDs. However, no correlation between gastric lesion index and depletion of PGE2 gastric levels was observed after treatment with ZAC (r = 0.012; p < 0.948). These data corroborate the hypothesis that preservation of the capability to synthesize endogenous PGs is of critical importance in the maintenance of gastric mucosal integrity. The gastroprotective action observed with ZAC involves alternative mechanisms other than modification of PGE2 levels.

  14. Risk factors associated with the development of gastroduodenal ulcers due to the use of NSAIDs.

    Science.gov (United States)

    Wolfe, M Michael

    2003-04-01

    The risk of gastrointestinal mucosal injury with non-steroidal anti-inflammatory drugs (NSAIDs) is dose-dependent. Epidemiological studies have clearly demonstrated a rank order of risk of ulcer complications for commonly used NSAIDs, with ibuprofen consistently associated with the lowest risk and piroxicam with the highest. Antacids, H2 receptor antagonists and misoprostol all have drawbacks as prophylaxis. Of the cyclo-oxygenase (COX)-2 selective NSAIDs, rofecoxib is associated with a lower risk of gastrointestinal toxicity but there is uncertainty about the long-term risk associated with celecoxib. Rofecoxib has been associated with a significantly higher incidence of myocardial infarction than naproxen that may counteract the benefit of greater gastrointestinal safety. At over-the-counter doses, the short duration of use and the low dose reduce the risk of a serious adverse event compared with chronic use at prescribed doses. Intermittent therapy with low-dose NSAIDs has proved extremely safe and it has not been determined whether COX-2 selective agents offer a safety advantage compared with such treatment.

  15. Thermo-sensitive injectable hydrogel based on the physical mixing of hyaluronic acid and Pluronic F-127 for sustained NSAID delivery.

    Science.gov (United States)

    Jung, Young-Seok; Park, Wooram; Park, Hyejin; Lee, Deok-Keun; Na, Kun

    2017-01-20

    The aim of this research is the development of a new type of intra-articularly injectable thermo-sensitive hydrogels for the long-term delivery of Piroxicam (PX). The thermo-sensitive hydrogel was prepared by the simple physical mixing of HA and Pluronic F-127 (HP) in aqueous solution. The addition of high-molecular-weight HA not only enhanced the mechanical strength of the hydrogel but also elicited a sustained drug release. This result could be attributed to the high-molecular-weight HA-assisted inter-micellar packing in the hydrogel inner structure. The critical gelation temperature value of HP hydrogel was considerably lower than native Pluronic F-127. To evaluate the bioavailability, pharmacokinetic parameters were analyzed after articular-cavity injection of the HP hydrogel in beagle dogs. The HP hydrogel exhibits both sustained drug release behavior and superior bioavailability in physiological conditions. Thus, we believe that the NSAID PX-loaded HP hydrogel could be a promising hydrogel-based drug delivery platform for the treatment of arthritis.

  16. High-performance liquid chromatography analysis of anti-inflammatory pharmaceuticals with ultraviolet and electrospray-mass spectrometry detection in suspected counterfeit homeopathic medicinal products.

    Science.gov (United States)

    Panusa, Alessia; Multari, Giuseppina; Incarnato, Giampaolo; Gagliardi, Luigi

    2007-03-12

    A simple high-performance liquid chromatography (HPLC) method with both ultraviolet (UV) and electrospray ionisation mass spectrometry (ESI-MS) detection has been developed for the determination of seven pharmaceuticals in counterfeit homeopathic preparations. Naproxen, Ketoprofen, Ibuprofen, Diclofenac, Piroxicam, Nimesulide and Paracetamol were separated by reversed phase chromatography with acetonitrile-water (0.1% acetic acid) mobile phase, and detected by UV at 245 nm and by ESI-MS in negative ionisation mode with the exception of Paracetamol which was detected in positive ionisation mode. Benzoic acid was used as internal standard (IS). This method was successfully applied to the analysis of homeopathic preparations like mother tinctures, solutions, tablets, granules, creams, and suppositories. Linearity was studied with UV detection in the 50-400 microg mL(-1) range and with ESI-MS in the 0.1-50 microg mL(-1) range. Good correlation coefficients were found in both UV and ESI-MS. Detection limits ranged from 0.18 to 41.5 ng in UV and from 0.035 to 1.00 ng in ESI-MS.

  17. Development of Oromucosal Dosage Forms by Combining Electrospinning and Inkjet Printing.

    Science.gov (United States)

    Palo, Mirja; Kogermann, Karin; Laidmäe, Ivo; Meos, Andres; Preis, Maren; Heinämäki, Jyrki; Sandler, Niklas

    2017-03-06

    Printing technology has been shown to enable flexible fabrication of solid dosage forms for personalized drug therapy. Several methods can be applied for tailoring the properties of the printed pharmaceuticals. In this study, the use of electrospun fibrous substrates in the fabrication of inkjet-printed dosage forms was investigated. A single-drug formulation with lidocaine hydrochloride (LH) and a combination drug system containing LH and piroxicam (PRX) for oromucosal administration were prepared. The LH was deposited on the electrospun and cross-linked gelatin substrates by inkjet printing, whereas PRX was incorporated within the substrate fibers during electrospinning. The solid state analysis of the electrospun substrates showed that PRX was in an amorphous state within the fibers. Furthermore, the results indicated the entrapment and solidification of the dissolved LH within the fibrous gelatin matrix. The printed drug amount (2-3 mg) was in good correlation with the theoretical dose calculated based on the printing parameters. However, a noticeable degradation of the printed LH was detected after a few months. An immediate release (over 85% drug release after 8 min) of both drugs from the printed dosage forms was observed. In conclusion, the prepared electrospun gelatin scaffolds were shown to be suitable substrates for inkjet printing of oromucosal formulations. The combination of electrospinning and inkjet printing allowed the preparation of a dual drug system.

  18. Soluplus graft copolymer: potential novel carrier polymer in electrospinning of nanofibrous drug delivery systems for wound therapy.

    Science.gov (United States)

    Paaver, Urve; Tamm, Ingrid; Laidmäe, Ivo; Lust, Andres; Kirsimäe, Kalle; Veski, Peep; Kogermann, Karin; Heinämäki, Jyrki

    2014-01-01

    Electrospinning is an effective method in preparing polymeric nanofibrous drug delivery systems (DDSs) for topical wound healing and skin burn therapy applications. The aim of the present study was to investigate a new synthetic graft copolymer (Soluplus) as a hydrophilic carrier polymer in electrospinning of nanofibrous DDSs. Soluplus (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PCL-PVAc-PEG)) was applied in the nonwoven nanomats loaded with piroxicam (PRX) as a poorly water-soluble drug. Raman spectroscopy, X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy (SEM) were used in the physical characterization of nanofibrous DDSs. According to the SEM results, the drug-loaded PCL-PVAc-PEG nanofibers were circular in cross-section with an average diameter ranging from 500 nm up to 2  µm. Electrospinning stabilized the amorphous state of PRX. In addition, consistent and sustained-release profile was achieved with the present nanofibrous DDSs at the physiologically relevant temperature and pH applicable in wound healing therapy. In conclusion, electrospinning can be used to prepare nanofibrous DDSs of PCL-PVAc-PEG graft copolymer (Soluplus) and to stabilize the amorphous state of a poorly water-soluble PRX. The use of this synthetic graft copolymer can open new options to formulate nanofibrous DDSs for wound healing.

  19. A step toward development of printable dosage forms for poorly soluble drugs.

    Science.gov (United States)

    Raijada, Dhara; Genina, Natalja; Fors, Daniela; Wisaeus, Erik; Peltonen, Jouko; Rantanen, Jukka; Sandler, Niklas

    2013-10-01

    The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkjet printing (PIJ) and impression printing (flexography). The printed dosage forms were characterized using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and the amount of drug was determined using high-performance liquid chromatography. Solutions of PRX in polyethylene glycol 400 (PEG-400):ethanol (40:60) and in PEG-400 were found to be optimal formulations for PIJ and flexography, respectively. SEM-EDX analysis revealed no visible solid particles on the printed dosage forms indicating the drug most likely remained in solution after printing. More accurate drug deposition was obtained by PIJ as compared with flexography. More than 90% drug release was achieved within 5 min regardless of printing method used. The solubility of drug in solvents/cosolvents, rheological properties of formulations, properties of substrate, feasibility and accuracy of the printing methods, and detection limit of analytical techniques for characterization of printed dosage forms are some of the concerns that need to be addressed for development of printable dosage forms of poorly soluble drugs.

  20. Concentration of non-steroidal anti-inflammatory drugs in the pelvic floor muscles: an experimental comparative rat model.

    Science.gov (United States)

    Chin, Hung-Yen; Changchien, Eileen; Lin, Mei-Fung; Chiang, Chi-Hsin; Wang, Chin-Jung

    2014-07-01

    The aim of this study is to explore non-steroid anti-inflammation drugs (NSAIDs) potency for pelvic floor muscle pain by measuring local concentration in a rat model. We used nine NSAIDs, including nabumetone, naproxen, ibuprofen, meloxicam, piroxicam, diclofenac potassium, etodolac, indomethacin, and sulindac, and 9 groups of female Wister rats. Each group of rats was fed with one kind of NSAID (2 mg/mL) for three consecutive days. Thereafter, one mL of blood and one gram of pelvic floor muscle were taken to measure drug pharmacokinetics, including partition coefficient, lipophilicity, elimination of half-life (T1/2) and muscle/plasma converting ratio (Css, muscle/Css, plasma). Diclofenac potassium had the lowest T1/2 and the highest mean Css, muscle/Css, plasma (1.9 hours and 0.85±0.53, respectively). The mean Css, muscle/Css, plasma of sulindac, naproxen and ibuprofen were lower than other experimental NSAIDs. Diclofenac potassium had the highest disposition in pelvic floor muscle in a rat model. The finding implies that diclofenac potassium might be the choice for pain relief in pelvic muscle.

  1. Synthesis, Structure, and Analgesic Properties of Halogen-Substituted 4-Hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxanilides

    Science.gov (United States)

    Ukrainets, Igor V.; Petrushova, Lidiya A.; Shishkina, Svitlana V.; Sidorenko, Lyudmila V.; Sim, Galina; Kryvanych, Olga V.

    2016-01-01

    As potential new analgesics, the corresponding 4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxanilides have been obtained by amidation of ethyl 4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylate with aniline and its halogenated analogsin boiling dry xylene. The peculiarities of the mass and nuclear magnetic resonance (1Н and 13С) spectra of the synthesized compounds are discussed. Using X-ray diffraction analysis, the ability of the compounds to form stable solvates with N,N-dimethylformamide has been shown on the example of 4-bromo-substituted derivative. It should be further studied to be considered in their crystallization. According to the results of the pharmacological testing conducted on the model of the thermal tail-flick (tail immersion test) among halogen-substituted 4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxanilides, substances which are considerably superior to meloxicam and piroxicam by their analgesic activity have been found. They are of interest for further profound studies. PMID:28117318

  2. FACTORS AFFECTING PHARMACOKINETIC DISPOSITION OF DRUGS

    Directory of Open Access Journals (Sweden)

    Mehta Hiren R

    2011-05-01

    Full Text Available Absorption of drugs from the gastrointestinal tract is a complex process the variability of which is influenced by many physicochemical and physiologic factors. The two most important physicochemical factors that affect both the extent and the rate of absorption are lipophilicity and solubility. The rate and extent of absorption are governed by the solubility, permeability and stability of the drug, with solubility being a pH-dependent parameter for weak acids and bases. The gastrointestinal tract can be viewed as discrete sections with a variety of differential local pH environments ranging from the acidic stomach to the more basic small intestine. The multiple peaking, double peaking or secondary peaking phenomena can occur in the disposition of a variety of xenobiotics during drug development (the pre-clinical phase and in subsequent clinical studies and use. The physicochemical and physiological mechanisms underlying the occurrence of this phenomenon are often multi factorial and include but are not limited to solubility-limited absorption, modified-release formulations, complexation, enterohepatic recirculation, gastric emptying and the intestinal transit time, site-specific absorption, gastric secretion-enteral reabsorption. Double peak absorption has been described with several orally administered drugs such as cimetidine furosemide, piroxicam, ranitidine, talinolol, alprazolam and phenazopyridine.

  3. New metal based drugs: Spectral, electrochemical, DNA-binding, surface morphology and anticancer activity properties

    Science.gov (United States)

    Çeşme, Mustafa; Gölcü, Aysegul; Demirtaş, Ibrahim

    2015-01-01

    The NSAID piroxicam (PRX) drug was used for complex formation reactions with Cu(II), Zn(II) and Pt(II) metal salts have been synthesized. Then, these complexes have been characterized by spectroscopic and analytical techniques. Thermal behavior of the complexes were also investigated. The electrochemical properties of all complexes have been investigated by cyclic voltammetry (CV) using glassy carbon electrode. The biological activity of the complexes has been evaluated by examining their ability to bind to fish sperm double strand DNA (FSFSdsDNA) with UV spectroscopy. UV studies of the interaction of the PRX and its complexes with FSdsDNA have shown that these compounds can bind to FSdsDNA. The binding constants of the compounds with FSdsDNA have also been calculated. The morphology of the FSdsDNA, PRX, metal ions and metal complexes has been investigated by scanning electron microscopy (SEM). To get the SEM images, the interaction of compounds with FSdsDNA has been studied by means of differential pulse voltammetry (DPV) at FSdsDNA modified pencil graphite electrode (PGE). The decrease in intensity of the guanine oxidation signals has been used as an indicator for the interaction mechanism. The effect of proliferation PRX and complexes were examined on the HeLA and C6 cells using real-time cell analyzer with four different concentrations.

  4. Synthesis, Spatial Structure and Analgesic Activity of Sodium 3-Benzylaminocarbonyl-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazin-4-olate Solvates

    Science.gov (United States)

    Ukrainets, Igor V.; Petrushova, Lidiya A.; Shishkina, Svitlana V.; Grinevich, Lina A.; Sim, Galina

    2016-01-01

    In order to obtain and then test pharmocologically any possible conformers of the new feasible analgesic N-benzyl-4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide, its 4-O-sodium salt was synthesized using two methods. X-ray diffraction study made possible to determine that, depending on the chosen synthesis conditions, the above-mentioned compound forms either monosolvate with methanol or monohydrate, where organic anion exists in the form of three different conformers. Pharmacological testing of the two known pseudo-enantiomeric forms of the original N-benzylamide and of the two solvates of its sodium salt was performed simultaneously under the same conditions and in equimolar doses. Comparison of the results obtained while studying the peculiarities of the synthesized compounds spatial structure and biological properties revealed an important structure-action relationship. In particular, it was shown that the intensity of analgesic effect of different conformational isomers of N-benzyl-4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide may change considerably: while low active conformers are comparable with piroxicam, highly active conformers are more than twice as effective as meloxicam. PMID:27775559

  5. The memory formalism in the diffusion of drugs through skin membrane

    Science.gov (United States)

    Caputo, Michele; Cametti, Cesare

    2009-06-01

    The diffusion of drugs across a composite structure such as a biological membrane is a rather complex phenomenon, where the assumptions on which the Fick equations are based are not always true, because of the inhomogeneous nature of the lipid membrane, the diffusion rate and the solubility of the drug being strongly dependent on the local position across the membrane. These problems are particularly strengthened in composite structures of a considerable thickness such as the human skin, where the high heterogeneity provokes the transport through different simultaneous pathways. In this note, we generalize the diffusion model based on Fick's second equation by the introduction of a space-dependent diffusion constant within the memory formalism (diffusion with memory) approach. The model predictions have been compared with experimental results concerning the permeation of two different compounds through human skin in vivo, such as piroxicam, an anti-inflammatory drug and 4-cyanophenol, a test chemical model compound. In both cases, reasonably good agreement has been found.

  6. Hierarchically structured self-supported latex films for flexible and semi-transparent electronics

    Science.gov (United States)

    Määttänen, Anni; Ihalainen, Petri; Törngren, Björn; Rosqvist, Emil; Pesonen, Markus; Peltonen, Jouko

    2016-02-01

    Different length scale alterations in topography, surface texture, and symmetry are known to evoke diverse cell behavior, including adhesion, orientation, motility, cytoskeletal condensation, and modulation of intracellular signaling pathways. In this work, self-supported latex films with well-defined isotropic/anisotropic surface features and hierarchical morphologies were fabricated by a peel-off process from different template surfaces. In addition, the latex films were used as substrates for evaporated ultrathin gold films with nominal thicknesses of 10 and 20 nm. Optical properties and topography of the samples were characterized using UV-vis spectroscopy and Atomic Force Microscopy (AFM) measurements, respectively. The latex films showed high-level transmittance of visible light, enabling the fabrication of semi-transparent gold electrodes. Electrochemical impedance spectroscopy (EIS) measurements were carried out for a number of days to investigate the long-term stability of the electrodes. The effect of 1-octadecanethiol (ODT) and HS(CH2)11OH (MuOH) thiolation and protein (human serum albumin, HSA) adsorption on the impedance and capacitance was studied. In addition, cyclic voltammetry (CV) measurements were carried out to determine active medicinal components, i.e., caffeic acid with interesting biological activities and poorly water-soluble anti-inflammatory drug, piroxicam. The results show that the fabrication procedure presented in this study enables the formation of platforms with hierarchical morphologies for multimodal (optical and electrical) real-time monitoring of length-scale-dependent biomaterial-surface interactions.

  7. Effect of Cyclodextrin Types and Co-Solvent on Solubility of a Poorly Water Soluble Drug

    Science.gov (United States)

    Charumanee, Suporn; Okonogi, Siriporn; Sirithunyalug, Jakkapan; Wolschann, Peter; Viernstein, Helmut

    2016-01-01

    The aim of the study was to investigate the solubility of piroxicam (Prx) depending on the inclusion complexation with various cyclodextrins (CDs) and on ethanol as a co-solvent. The phase-solubility method was applied to determine drug solubility in binary and ternary systems. The results showed that in systems consisting of the drug dissolved in ethanol–water mixtures, the drug solubility increased exponentially with a rising concentration of ethanol. The phase solubility measurements of the drug in aqueous solutions of CDs, β-CD and γ-CD exhibited diagrams of AL-type, whereas 2,6-dimethyl-β-CD revealed AP-type. The destabilizing effect of ethanol as a co-solvent was observed for all complexes regardless of the CD type, as a consequence of it the lowering of the complex formation constants. In systems with a higher concentration of ethanol, the drug solubility was increased in opposition to the decreasing complex formation constants. According to this study, the type of CDs played a more important role on the solubility of Prx, and the use of ethanol as a co-solvent exhibited no synergistic effect on the improvement of Prx solubility. The Prx solubility was increased again due to the better solubility in ethanol. PMID:27763573

  8. POLYURETHANE COMPOSITES AS DRUG CARRIERS:: RELEASE PATTERNS

    Directory of Open Access Journals (Sweden)

    M. V. Grigoreva

    2013-10-01

    Full Text Available Biodegradable polyurethanes attract interest of those developing composite materials for biomedical applications. One of their features is their ability to serve as carriers, or matrixes, for medicines and other bioactive compounds to produce a therapeutic effect in body through targeted and/or prolonged delivery of these compounds in the process of their controlled release from matrix. The review presents polyurethane composites as matrices for a number of drugs. The relation between structure of the composites and their degradability both in vitro and in vivo and the dependence of drug release kinetics on physicochemical properties of polyurethane matrix are highlighted. The release of drugs (cefazolin, naltrexone and piroxicam from the composites based on cross-linked polyurethanes (synthesized from laprols, Mw between 1,500 and 2,000 Da and toluylene diisocyanate demonstrated more or less the same pattern (about 10 days in vitro and three to five days in vivo. In contrast, the composites with dioxydine based on a linear polyurethanes (synthesized from oligotetramethilene glycol, Mw 1,000 Da, diphenylmethane-4,4’-diisocyanate and 1,4-butanediol retained their antimicrobial activity at least 30 days. They also showed a significantly higher breaking strength as compared to that of the composites based on cross-linked polyurethanes.

  9. SUITABILITY OF MEDICATIONS USED BY THE ELDERLY PARTICIPANTS OF A SOCIAL GROUP, ACCORDING TO THE BEERS CRITERIA

    Directory of Open Access Journals (Sweden)

    Geysa Donária de Miranda Mascarenhas

    2014-09-01

    Full Text Available The dynamic process defined as aging progressively reduces the functional capacity of the elderly and added to the lifestyle, they can to testify to the high number of pathologies. Thus, pharmacotherapy for this age group requires special care, keeping in view its peculiarities. Given this need, a group of researchers has developed criteria that allowed the identification of inappropriate medications. Thus, the aim of this study was to investigate the suitability of medications used by the elderly participants of a social group, in Vitória da Conquista, BA, according to the Beers criteria. This research was an exploratory descriptive study and data collection conducted through semi - structured interviews. It was asked to bring all the elderly who were using medications and / or prescriptions. It was found that 12.7% of the drugs used by the elderly appeared in the list of inappropriate medicines and 42% of respondents make use of polypharmacy. Among the most prescribed inappropriate medications, there is acetylsalicylic acid, diclofenac, diazepam, piroxicam, ibuprofen and amitriptyline. The class of inappropriate drugs most used by seniors was anti - inflammatory drugs. Given this, all health professionals need to put into practice the criteria for selecting medications this age group as the reality of existing drugs in Brazil.

  10. 电致孔经皮给药:表面活性剂对孔道存在时间和药物传输的影响%Transdermal Drug Delivery by Electroporation: The Effects of Surfactants on Pathway Lifetime and Drug Transport

    Institute of Scientific and Technical Information of China (English)

    蒋国强; 朱德权; 咎佳; 丁富新

    2007-01-01

    Electroporation creates aqueous pathways by short high-voltage pulses resulting in a transient permeabilization of stratum corneum and an increase in the transdermal delivery rate.However the aqueous pathways will reseal after pulsing, which leads to the rapid drop of transdermal flux.In the present study, the surfactants were added to the donor solution to hinder the shrinkage and resealing of the electropore, and to prolong the lifetime of the aqueous pathways with the consideration that the surfactants could reduce the surface energy of the electropore.These effects of surfactants were demonstrated by the dynamic electrical resistance of the skin and the fluorescent imaging of the local transport regions.Piroxicam (FIX) was transported percutaneously in the presence of surfactants in vitro.Owing to the longer lifetime of aqueous pathways, together with the promotion of FIX availability at the barrier exterior and the improvement in the partition of FIX into the aqueous pathways, the presence of surfactants led to a remarkable increase in the transdermal delivery rate during electroporation and a significant growth of the accumulative transdermal amount of FIX.

  11. Synthetic Zeolites as Controlled-Release Delivery Systems for Anti-Inflammatory Drugs.

    Science.gov (United States)

    Khodaverdi, Elham; Soleimani, Hossein Ali; Mohammadpour, Fatemeh; Hadizadeh, Farzin

    2016-06-01

    Scientists have always been trying to use artificial zeolites to make modified-release drug delivery systems in the gastrointestinal tract. An ideal carrier should have the capability to release the drug in the intestine, which is the main area of absorption. Zeolites are mineral aluminosilicate compounds with regular structure and huge porosity, which are available in natural and artificial forms. In this study, soaking, filtration and solvent evaporation methods were used to load the drugs after activation of the zeolites. Weight measurement, spectroscopy FTIR, thermogravimetry and scanning electronic microscope were used to determine drug loading on the systems. Finally, consideration of drug release was made in a simulated gastric fluid and a simulated intestinal fluid for all matrixes (zeolites containing drugs) and drugs without zeolites. Diclofenac sodium (D) and piroxicam (P) were used as the drug models, and zeolites X and Y as the carriers. Drug loading percentage showed that over 90% of drugs were loaded on zeolites. Dissolution tests in stomach pH environment showed that the control samples (drug without zeolite) released considerable amount of drugs (about 90%) within first 15 min when it was about 10-20% for the matrixes. These results are favorable as NSAIDs irritate the stomach wall and it is ideal not to release much drugs in the stomach. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples in intestine pH environment.

  12. Enhancement by platelets of oxygen radical responses of human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    McCulloch, K.K.; Powell, J.; Johnson, K.J.; Ward, P.A.

    1986-03-01

    When human blood neutrophils were incubated with immune complexes (consisting of IgG antibody) in the presence of platelets, there was a 2 to 10 fold enhancement in the generation of O-/sub 2/ and H/sub 2/O/sub 2/. This enhancement phenomenon was proportional to the dose of immune complex added and the number of platelets present. The response was not agonist specific since similar enhancement also occurred with the following agonists: phorbol myristate acetate, opsonized zymosan particles and the chemotactic peptide N-formyl-met-leu-phe. The platelet related phenomenon of enhanced O-/sub 2/ generation could not be reproduced by the addition of serotonin, histamine or platelet-derived growth factor and was not affected by prior treatment of platelets with cyclooxygenase inhibitors (indomethacin, piroxicam) or lipoxygenase inhibitors (nafazatrom, BW755C or nordihydroguaiaretic acid). However, activation of platelets by thrombin caused release into the platelet supernatant fluid of a factor that, only in the presence of immune complexes, caused enhanced O-/sub 2/ responses to neutrophils. These data indicate that platelets potentiate oxygen radical responses of human neutrophils and suggest a mechanisms by which platelets may participate in tissue injury which is mediated by oxygen radical products from activated neutrophils.

  13. The memory formalism in the diffusion of drugs through skin membrane

    Energy Technology Data Exchange (ETDEWEB)

    Caputo, Michele; Cametti, Cesare, E-mail: cesare.cametti@roma1.infn.i [Dipartimento di Fisica, Universita di Roma ' La Sapienza' , Piazzale A. Moro 2, I-00185 Rome (Italy) and CNR-INFM-SOFT, Unita di Roma1 Rome (Italy)

    2009-06-21

    The diffusion of drugs across a composite structure such as a biological membrane is a rather complex phenomenon, where the assumptions on which the Fick equations are based are not always true, because of the inhomogeneous nature of the lipid membrane, the diffusion rate and the solubility of the drug being strongly dependent on the local position across the membrane. These problems are particularly strengthened in composite structures of a considerable thickness such as the human skin, where the high heterogeneity provokes the transport through different simultaneous pathways. In this note, we generalize the diffusion model based on Fick's second equation by the introduction of a space-dependent diffusion constant within the memory formalism (diffusion with memory) approach. The model predictions have been compared with experimental results concerning the permeation of two different compounds through human skin in vivo, such as piroxicam, an anti-inflammatory drug and 4-cyanophenol, a test chemical model compound. In both cases, reasonably good agreement has been found.

  14. Study on the Release Process of Drug-containing PMMA Film by Two-dimensional UV-Vis Correlation Spectroscopy%二维紫外相关光谱研究复方载药PMMA膜的释放过程

    Institute of Scientific and Technical Information of China (English)

    江艳; 武培怡

    2008-01-01

    用紫外一可见光谱(UV-Vis spectroscopy)表征载有布洛芬(ibuprofen)和吡罗昔康(piroxicam)复方药物的聚甲基丙烯酸甲酯(PMMA)膜在磷酸盐缓冲溶液(PBS)中的释放过程,观察两种药物在时间外扰下的释放情况.随着时间的推移,两种药物都保持了持久的释放.同时,通过二维紫外相关光谱(two-dimensional UV correlation spectroscopy)米进一步探究两种药物从PMMA膜内释放到缓冲溶液中的先后顺序,推断出布洛芬与PMMA之间形成了一定的氢键相互作用,导致释放速度变缓.复方载药膜的红外光谱证明了这种相互作用的存在,验证了二维紫外相关光谱在药物缓释领域的潜在应用价值.

  15. Clinical, Epidemiological and Therapeutic Evaluation in 14 Cases of Inflammatory Breast Cancer in Canines

    Directory of Open Access Journals (Sweden)

    Celina Gomes da Silva

    2014-06-01

    Full Text Available With the aim of evaluating clinical aspects, age, breed, presence of metastasis, chemotherapeutical protocol, use of COX-2 inhibitors and survival rate in female dogs diagnosed with inflammatory carcinoma at the Hospital Veterinario de Uberaba (HVU, a retrospective analysis was performed on the medical records of 14 female dogs seen at HVU between July, 2011 and July, 2012 and diagnosed with inflammatory breast cancer. The breeds included were crossbred, poodle, Brazilian terrier, teckel and Belgian shepherd. Average age: 11.1 years. Outbreaks of distant metastasis were detected in 7 animals, out of which 5 patients received COX-2 inhibitors as sole treatment and only 4 received chemotherapeutical treatment. The protocol, constituted by piroxicam, cyclophosphamide, carboplatin and doxorubicin showed the highest survival time (210 days. In conclusion, inflammatory carcinoma is a disease of bad prognosis, short survival time and produces systemic alterations that reduce therapeutic response. Apparently, the most accurate therapeutic form is the association of COX-2 inhibitors and chemotherapeutics; however, controlled clinical studies are needed in order to evaluate these suggestions.

  16. Stevens–Johnson syndrome and toxic epidermal necrolysis in an academic hospital setting: a 5-year retrospective study

    Directory of Open Access Journals (Sweden)

    Ewa Stocka-Łabno

    2016-10-01

    Full Text Available Introduction: Toxic epidermal necrolysis and Stevens–Johnson syndrome are acute life-threatening mucocutaneous reactions to drugs. The aims of the study were to identify these drugs and characterize population prone to these reactions. Materials and Methods: Data including demographics, culprit drug, clinical characteristics, course of disease, treatment given, and therapeutic responses were retrospectively collected from medical records of 31 patients admitted to Department of Dermatology from January 2009 to December 2014. Results: Drugs most commonly involved in Stevens–Johnson syndrome were antimicrobials: ciprofloxacin, doxycycline, cefuroxime, trimethoprim, amoxicillin, clindamycin, co-trimoxazole (50% of patients and nonsteroidal anti-inflammatory drugs: ibuprofen, naproxen, metamizole, piroxicam (29% of patients. Drugs involved in toxic epidermal necrolysis were antimicrobials: sulfasalazine, co-trimoxazole, cefuroxime, clindamycin (71% of patients and anticonvulsants: lamotrigine (29% of patients. The comorbidities’ characteristic for the group of patients affected by toxic epidermal necrolysis were psychiatric and autoimmune disorders. The most common complication was infection. Two patients died and in both cases the cause of death was sepsis. Conclusion: The study indicates that in observed population drugs with the highest risk of most severe reactions are lamotrigine (anticonvulsant and antimicrobials (most commonly sulfonamides, therefore it is advisable to consider carefully administration of these drugs, especially to patients with history of autoimmune reactions.

  17. Unusual interleukin-1 and -6 expression in fetal cartilage is associated with placental abnormalities.

    Directory of Open Access Journals (Sweden)

    Robert Klepacz

    2010-06-01

    Full Text Available Unusual expression of interleukin-1alpha, -1beta and -6 was previously found in the epiphyseal cartilage of rat fetuses prenatally exposed to various non-steroidal anti-inflammatory drugs (NSAID, i.e., ibuprofen, piroxicam, tolmetin and selective cyclooxygenase-2 inhibitor (DFU. The aim of the present study was to evaluate the role of placenta in such phenomenon. Morphology of the organ, thickness of basal and labyrinth layer, immunoexpression of COX isoenzymes were examined, and confronted with maternal biochemical data and fetal developmental parameters. Higher maternal urea level, as well as lower placental weight and labyrinth thickness were found in the group of fetuses who revealed expression of genes coded the selected interleukins, when compared with the xenobiotic-exposed pups without the selected genes expression and untreated control. A significant correlation between placental weight and maternal total protein or urea level was revealed. Histological changes like inflammatory infiltration and calcification were observed sporadically. Location and intensity of COX-1 staining was similar in all cases. However, more intense COX-2 staining for majority of cells of the basal zone and in dispersed giant cells of the labyrinth was found in inflamed organs. It could be concluded that abnormal expression of the selected interleukins is associated with low placental weight and decrease of its thickness, especially labyrinth zone, as well as with high maternal urea level.

  18. Effects of benzydamine eye drops on the rabbit's eye reaction to surgical, physical, and chemical stimuli

    Energy Technology Data Exchange (ETDEWEB)

    Tomazzoli, L.; Bonora, A.; Luparini, M.R.; Durando, L.; Ciarniello, M.G.; Cioli, V.; Bonomi, L.

    The effects of benzydamine eye drops on the ocular reaction to different irritating stimuli in rabbits are reported. Benzydamine at the concentration of 0.1% reduces inflammatory tissue changes induced by AgNO3 burning of the cornea and inhibits the blood-aqueous barrier breakdown due to peripheral iridectomy or laser irradiation of the iris. Benzydamine reduces the aqueous PGE2 concentration to a similar extent as a 0.5% commercially available eye drop formulation of piroxicam. This result is in contrast with previous in vitro results demonstrating that benzydamine is devoid of any effects on PG synthesis. The possibility that PGE2 reduction is an indirect effect due to other biochemical activities of benzydamine is discussed. In the normal eye benzydamine manifests a local anaesthetic effect which is not accompanied by irritative changes in the anterior segment of the eye, changes in the intraocular pressure or pupillary size. It is suggested that in the clinical use of benzydamine eye drops the local anaesthetic activity may contribute to reducing both the neurogenic component of ocular inflammation and acute pain following injuries to the eye.

  19. Radiation proctitis in the rat. Sequential changes and effects of anti-inflammatory agents

    Energy Technology Data Exchange (ETDEWEB)

    Northway, M.G.; Scobey, M.W.; Geisinger, K.R.

    1988-11-01

    Female Wistar rats were treated with single exposure irradiation to 2 cm of distal colon to cause radiation proctitis. All animals were evaluated by examination, colonoscopy and histologic evaluation for changes post-irradiation. Exposures of 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5 and 30 Gy caused dose-related clinical and histologic changes peaking at 7 to 15 days post-exposure. Rats treated with 20 Gy were colonoscoped and biopsied daily and showed sequential post-irradiation endoscopic changes ranging from mucosal edema and mild inflammatory changes to erosion and ulcers. Histologically, crypt abscess and mural wall necrosis similar to changes found in the human rectum after radiotherapy were noted. Treatment with nonsteroidal anti-inflammatory agents, (aspirin, indomethacin, piroxicam), misoprostol (a prostaglandin E1 analogue), or sucralfate (an anti-ulcer agent) did not ameliorate nor exacerbate radiation proctitis in rats exposed to 22.5 Gy. We conclude from these data that the female Wistar rat is a good model for studying radiation proctitis because endoscopic, histologic, and clinical changes seen post-exposure closely resemble those found in man.

  20. Polymorphic behavior of isonicotinamide in cooling crystallization from various solvents

    Science.gov (United States)

    Hansen, Thomas B.; Taris, Alessandra; Rong, Ben-Guang; Grosso, Massimiliano; Qu, Haiyan

    2016-09-01

    In this work the nucleation of different polymorphs of isonicotinamide (INA) from different solvents has been studied. The metastable zone width of INA in cooling crystallization from five different solvents has been investigated and attempts have been made to reveal the link between the INA molecular self-association to the polymorphism of the nucleated crystals using ATR FT-IR (Attenuated Total Reflectance Fourier Transform Infrared) and Raman spectroscopy. Raman and IR spectra of INA dissolved in different solvents have demonstrated that the INA molecules might associate in different configurations, whereas, the link between the structure of the molecular self-association and the structure of the nucleated polymorph is complicated by the influence of INA concentration. This is consistent with our previous study with piroxicam. The cooling crystallization of INA from five different solvents resulted in two different polymorphs depending on the initial concentration of the solution. The results obtained in the present work showed that information about self-association of an API (Active Pharmaceutical Ingredient) in a given solvent is not sufficient to predict the polymorphic behavior in all scenarios.

  1. 喜来通

    Institute of Scientific and Technical Information of China (English)

    张鲜利; 崔敏; 杨威; 张明利

    2002-01-01

    @@ [通用名称] piroxicam-β-cyclodextrin,β-环糊精吡罗昔康片 [化学名称] 4-羟基-2-甲基-N-(2-吡啶基)-2氢-1,2-苯骈异噻嗪-3-羧酰胺-1,1-二氧 [理化性状] 本品在水中几乎不溶;溶于酸,略溶于碱.熔点198~202℃. [药理作用] 吡罗昔康为抗炎镇痛药,其抗炎作用可能部分由于抑制前列腺素合成所致[1].喜来通是由吡罗昔康与β- 环糊精构成的新型复合物,由于所具有的特殊化学结构改善了溶解度,使之更易溶于水.因此喜来通较单一的吡罗昔康有更快、更强的镇痛抗炎效果.由于它的药效学和药动学的特性,喜来通特别适用于急性炎性疼痛治疗.

  2. Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Gross, N.J.; Holloway, N.O.; Narine, K.R. (Medical Radiology Service, Hines VA Hospital, Maywood, IL (United States))

    1991-09-01

    Corticosteroids have previously been found to be protective against the mortality of radiation pneumonitis in mice, even when given well after lethal lung irradiation. The authors explored the possibility that this effect was due to their well-known anti-inflammatory actions by giving various nonsteroidal inhibitors of arachidonate metabolism to groups of mice that had received 19 Gy to the thorax (bilaterally). Treatments of four cyclooxygenase inhibitors, one lipoxygenase inhibitor, and one leukotriene receptor antagonist, given by various routes in various doses, were commenced 10 weeks after irradiation or sham irradiation and continued throughout the period when death from radiation pneumonitis occurs, 11-26 weeks after irradiation. Each of the treatments had the appropriate effect on arachidonate metabolism in the lungs as assessed by LTB4 and PGE2 levels in lung lavage fluid. The principal end point was mortality. The 5-lipoxygenase inhibitor diethylcarbamazine and the LTD4/LTE4 receptor antagonist LY 171883 markedly reduced mortality in dose-response fashion. The effects of cyclooxygenase inhibitors were divergent; piroxicam and ibuprofen were marginally protective, indomethacin in all doses accelerated mortality, and aspirin reduced mortality in a dose-response fashion. These results suggest that the protective effect of corticosteroids in radiation pneumonitis can be tentatively attributed to their anti-inflammatory actions, and that nonsteroidal anti-inflammatory agents, particularly those that affect lipoxygenase products, may offer equal or better protection than corticosteroids against mortality due to radiation pneumonitis.

  3. Amtolmetin: A Reappraisal of NSAID with Gastroprotection

    Directory of Open Access Journals (Sweden)

    Amit Garg

    2016-01-01

    Full Text Available Aim. To assess the gastrosparing effect of amtolmetin guacyl (AMG against other nonsteroidal anti-inflammatory drugs (NSAIDs in patients with osteo-/rheumatoid arthritis. Methods. A literature search was done in the electronic databases (PubMed, Google Scholar, Embase, and Scopus with key words “amtolmetin guacyl”, “amtolmetin”, and “arthritis”; filters were applied to obtain publications between 01-Jan-1985 and 01-Oct-2015, which were “clinical trials” in osteo-/rheumatoid arthritis patients and in “English language.” Studies were assessed using the Jadad criteria and trials with score ≥ 3 were included in the analysis to compare the safety and efficacy of AMG against other NSAIDs. Results. Search yielded 19 publications of which 3 were included for analysis. Baseline characteristics of patients were comparable between the AMG group and other NSAIDs (diclofenac, celecoxib, and piroxicam groups in all trials. Efficacy of AMG was similar to the other NSAIDs compared in the trials. The number of adverse events (AEs reported was similar between both the groups; however, severe AEs reported were significantly lower in the AMG group. Of note was the significant lower number of duodenal ulcers after treatment in the AMG group. Conclusions. AMG has efficacy similar to other NSAIDs and a safer gastrointestinal AE profile when compared to the other NSAIDs.

  4. Electroresponsive nanoparticles for drug delivery on demand

    Science.gov (United States)

    Samanta, Devleena; Hosseini-Nassab, Niloufar; Zare, Richard N.

    2016-04-01

    The potential of electroresponsive conducting polymer nanoparticles to be used as general drug delivery systems that allow electrically pulsed, linearly scalable, and on demand release of incorporated drugs is demonstrated. As examples, facile release from polypyrrole nanoparticles is shown for fluorescein, a highly water-soluble model compound, piroxicam, a lipophilic small molecule drug, and insulin, a large hydrophilic peptide hormone. The drug loading is about 13 wt% and release is accomplished in a few seconds by applying a weak constant current or voltage. To identify the parameters that should be finely tuned to tailor the carrier system for the release of the therapeutic molecule of interest, a systematic study of the factors that affect drug delivery is performed, using fluorescein as a model compound. The parameters studied include current, time, voltage, pH, temperature, particle concentration, and ionic strength. Results indicate that there are several degrees of freedom that can be optimized for efficient drug delivery. The ability to modulate linearly drug release from conducting polymers with the applied stimulus can be utilized to design programmable and minimally invasive drug delivery devices.

  5. Transport rankings of non-steroidal antiinflammatory drugs across blood-brain barrier in vitro models.

    Directory of Open Access Journals (Sweden)

    Iveta Novakova

    Full Text Available The aim of this work was to conduct a comprehensive study about the transport properties of NSAIDs across the blood-brain barrier (BBB in vitro. Transport studies with celecoxib, diclofenac, ibuprofen, meloxicam, piroxicam and tenoxicam were accomplished across Transwell models based on cell line PBMEC/C1-2, ECV304 or primary rat brain endothelial cells. Single as well as group substance studies were carried out. In group studies substance group compositions, transport medium and serum content were varied, transport inhibitors verapamil and probenecid were added. Resulted permeability coefficients were compared and normalized to internal standards diazepam and carboxyfluorescein. Transport rankings of NSAIDs across each model were obtained. Single substance studies showed similar rankings as corresponding group studies across PBMEC/C1-2 or ECV304 cell layers. Serum content, glioma conditioned medium and inhibitors probenecid and verapamil influenced resulted permeability significantly. Basic differences of transport properties of the investigated NSAIDs were similar comparing all three in vitro BBB models. Different substance combinations in the group studies and addition of probenecid and verapamil suggested that transporter proteins are involved in the transport of every tested NSAID. Results especially underlined the importance of same experimental conditions (transport medium, serum content, species origin, cell line for proper data comparison.

  6. Microfibrous Solid Dispersions of Poorly Water-Soluble Drugs Produced via Centrifugal Spinning: Unexpected Dissolution Behavior on Recrystallization.

    Science.gov (United States)

    Marano, Stefania; Barker, Susan A; Raimi-Abraham, Bahijja T; Missaghi, Shahrzad; Rajabi-Siahboomi, Ali; Aliev, Abil E; Craig, Duncan Q M

    2017-05-01

    Temperature-controlled, solvent-free centrifugal spinning may be used as a means of rapid production of amorphous solid dispersions in the form of drug-loaded sucrose microfibers. However, due to the high content of amorphous sucrose in the formulations, such microfibers may be highly hygroscopic and unstable on storage. In this study, we explore both the effects of water uptake of the microfibers and the consequences of deliberate recrystallization for the associated dissolution profiles. The stability of sucrose microfibers loaded with three selected BCS class II model drugs (itraconazole (ITZ), olanzapine (OLZ), and piroxicam (PRX)) was investigated under four different relative humidity conditions (11, 33, 53, and 75% RH) at 25 °C for 8 months, particularly focusing on the effect of the highest level of moisture (75% RH) on the morphology, size, drug distribution, physical state, and dissolution performance of microfibers. While all samples were stable at 11% RH, at 33% RH the ITZ-sucrose system showed greater resistance against devitrification compared to the OLZ- and PRX-sucrose systems. For all three samples, the freshly prepared microfibers showed enhanced dissolution and supersaturation compared to the drug alone and physical mixes; surprisingly, the dissolution advantage was largely maintained or even enhanced (in the case of ITZ) following the moisture-induced recrystallization under 75% RH. Therefore, this study suggests that the moisture-induced recrystallization process may result in considerable dissolution enhancement compared to the drug alone, while overcoming the physical stability risks associated with the amorphous state.

  7. Synthesis, Spatial Structure and Analgesic Activity of Sodium 3-Benzylaminocarbonyl-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazin-4-olate Solvates

    Directory of Open Access Journals (Sweden)

    Igor V. Ukrainets

    2016-10-01

    Full Text Available In order to obtain and then test pharmocologically any possible conformers of the new feasible analgesic N-benzyl-4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide, its 4-O-sodium salt was synthesized using two methods. X-ray diffraction study made possible to determine that, depending on the chosen synthesis conditions, the above-mentioned compound forms either monosolvate with methanol or monohydrate, where organic anion exists in the form of three different conformers. Pharmacological testing of the two known pseudo-enantiomeric forms of the original N-benzylamide and of the two solvates of its sodium salt was performed simultaneously under the same conditions and in equimolar doses. Comparison of the results obtained while studying the peculiarities of the synthesized compounds spatial structure and biological properties revealed an important structure-action relationship. In particular, it was shown that the intensity of analgesic effect of different conformational isomers of N-benzyl-4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide may change considerably: while low active conformers are comparable with piroxicam, highly active conformers are more than twice as effective as meloxicam.

  8. The Measurement of Meloxicam and Meloxicam Metabolites in Rat Plasma Using a High-Performance Liquid Chromatography-Ultraviolet Spectrophotometry Method.

    Science.gov (United States)

    Miyamoto, Aoi; Aoyama, Takahiko; Matsumoto, Yoshiaki

    2017-02-01

    A high-performance liquid chromatography-ultraviolet spectrophotometry (HPLC-UV) method for the determination of meloxicam (MEL) and meloxicam metabolites (5'-hydroxy meloxicam (5-HMEL) and 5'-carboxy meloxicam (5-CMEL)) has been developed. After extraction of MEL, 5-HMEL, and 5-CMEL from rat plasma using Oasis HLB cartridges, the extracts were separated with a Luna C18 (2) 100 A column (5 µm, 4.6×150 mm, Phenomenex) using a mobile phase of 50 mM phosphate buffer (pH 2.15, solvent A) and acetonitrile (solvent B) at a flow rate of 0.8 mL/min in a linear gradient. The detection wavelength was 360 nm, and the internal standard (IS) was piroxicam. Each calibration curve was linear in the range of 40 to 1000 ng/mL (r(2)>0.999). The extraction rates of MEL, 5-HMEL, and 5-CMEL were greater than 86.9%. The intra- and inter-day accuracies were in the range of 95.0 to 119.0%, and the precision was 0.2 to 17.0%. To the best of our knowledge, this is the first report of the quantitative and qualitative measurement of meloxicam and each metabolite using an HPLC-UV method.

  9. Comparison of Mass Transfer Models for Determination of the Intestinal Permeability

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    P Zakeri-Milani

    2008-09-01

    Full Text Available Background and the purpose of the study: In determination of the permeability of the intestinal wall by external perfusion techniques, several models have been proposed. In the present study three models were used for experimental results that differ in their convection and diffusion assumptions. Material and Methods: Permeability coefficients for 13 compounds (metoprolol, propranolol, naproxen, ketoprofen, furosemide, hydrochlorothiazide, cimetidine, ranitidine, atenolol, piroxicam, antipyrine, ibuprofen and carbamazepine with known human intestinal permeability values were determined in anaesthetized rats by different mass transfer models and plotted versus the observed human intestinal permeabilities. Results: The calculated dimensionless wall permeability values were in the range of 0.37 - 4.85, 0.38-6.54 and 0.41-16.59 for complete radial mixing, mixing tank and laminar flow models respectively. The results indicated that all of the models work relatively well for our data despite fundamentally different assumptions. The wall permeabilities were in the order laminar flow > mixing tank > complete radial mixing. Conclusion: Although laminar flow model provides the most direct measure of the intrinsic wall permeability, it has limitations for highly permeable drugs such as ibuprofen. The normal physiological hydrodynamics is more complex and more investigation is required to find out the real hydrodynamics.

  10. NSAID Antinociception Measured in a Chemical and a Thermal Assay in Mice

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    HF Miranda

    2001-01-01

    Full Text Available The antinociceptive activity of several nonsteroidal anti-inflammatory drugs (NSAIDs that were administered either intraperitoneally or intrathecally was assessed in mice by two algesiometric tests. The first was the writhing test, which assessed the abdominal constrictions that were induced by intraperitoneal acetic acid (a chemical test, and the second was the tail flick test, which measured pain responses to heat stimuli. The corresponding effective doses and their relative potencies were compared because these tests use different nociceptive stimuli with different transmission pathways. The intraperitoneal and intrathecal dose-response curves for the antinociception induced by every NSAID that was tested were parallel in the writhing test. In the tail flick test, however, only the intraperitoneal and intrathecal dose-response curves for ketoprofen, piroxicam, naproxen, nimesulide, paracetamol and diclofenac were parallel. The results obtained in this study confirm that NSAIDs possess different abilities to induce inhibition of cyclooxygenase, and they can be indirectly assessed by their different antinociceptive activities, depending on the algesiometric assays that are used. The antinociception of most NSAIDs might involve central mechanisms. The findings demonstrate the increasing importance of the spinal cord in processing and modulating nociceptive input, because intrathecal administration of NSAIDs is always more effective (in terms of potency than systemic administration; thus, the antinociceptive efficacy of NSAIDs strongly depends on the algesiometric assay that is used and on the type of the nociceptive stimulus to which the test subject is exposed.

  11. Influence of some anti-inflammatory drugs on the activity of aryl hydrocarbon hydroxylase and the cytochrome P450 content

    Energy Technology Data Exchange (ETDEWEB)

    Mostafa, M.H.; Sheweita, S.A.; Abdel-Moneam, N.M. (Alexandria Univ. (Egypt))

    1990-06-01

    The metabolism of benzo({alpha})pyrene is mediated by the mixed function oxidase system including the cytochrome P450-dependent aryl hydrocarbon hydroxylase. The data of the present study revealed the ability of various commonly used anti-inflammatory drugs to alter the activity of this enzyme system, where all the tested drugs, namely phenyl butazone, ketoprofen, piroxicam, and acetaminophen, caused an increase in both the activity of aryl hydrocarbon hydroxylase and the cytochrome P450 content whether administered as a single dose or as a repeated dose for 6 consecutive days. The percentage of change for all drugs except phenyl butazone was proportional to the duration of drug administration. On the other hand, pyrazole which is chemically related to phenyl butazone, had no significant effect when administered as a single dose but caused a decrease in both studied parameters when administered as a repeated dose for 6 consecutive days. The mechanisms by which these commonly used drugs modify the aryl hydrocarbon hydroxylase activity and the cytochrome p450 content are discussed in the text.

  12. Analisis Adulterasi Jamu Pegal Linu yang Diperoleh dari Pasar di Jakarta dan Sekitarnya (Analysis of Adulterated Jamu Pegal Linu Obtained from the Market in Jakarta

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    Retno Gitawati

    2014-04-01

    Full Text Available Background: “Jamu Pegal Linu” (traditional Indonesian herb for rheumatoid and gouty arthritis is one of the mostpopular jamu products manufactured and widely consumed in the community. Despite the claims that they are made ofnatural herbs, these kinds of jamu are susceptible for being counterfeited and adulterated with drugs that is potentiallyharmful for health. The aim of this study was to identify medicinal adulteration in jamu pegal linu products obtained from the market in Jakarta and surroundings. Method: This study was an experimental laboratory in a cross-sectional design. About 450 samples of jamu pegal linu products were randomly chosen, and the products with different brands wereanalyzed for medicinal adulteration using a thin layer chromatography (TLC method. Product labels of the adulterated jamu were also analyzed for the appropriateness of the product information. Results: Out of the 114 brands of jamu pegal linu analyzed, 52 samples (45.6% were positive for medicinal. The medicinal types detected were paracetamol (30.7%, phenylbutazone (20.4%, piroxicam (7.1% and mefenamic acid (3.5%. Two samples of jamu has been contaminated with molds and found damp. Of the 52 samples positive medicinal, 92.3% include the registration number and only 30.8% include the expiration date in the product labels. About 44.2% include the name of ingredients compositions written incorrectly in the labels. Conclusion: A. limited numbers of Jamu pegal linu products adulterated with medicinal still existed in the market.

  13. Computational nanochemistry report on the oxicams--conceptual DFT indices and chemical reactivity.

    Science.gov (United States)

    Martínez-Araya, Jorge Ignacio; Salgado-Morán, Guillermo; Glossman-Mitnik, Daniel

    2013-05-30

    A density functional theory study of eight oxicams was carried out in order to determine their global and local reactivities. These types of reactivities were measured by means of global and local reactivity descriptors coming from the conceptual density functional theory. Net electrophilicity as a global reactivity descriptor and local hypersoftness as a local reactivity descriptor were the used tools to distinguish reactivity and selectivity among these oxicams. Globally, isoxicam presents the highest electron donating capacity; meanwhile, the highest electron accepting capacity is exhibited by droxicam. Locally, two oxicams present neither nucleophilic nor electrophilic relevant reactivity in their peripheral pyridine ring, droxicam and tenoxicam, so that their more reactive zones are found on the respective fused rings. Oxicams have been divided into two subgroups in order to facilitate the local analysis of reactivity. One group is characterized because their most important condensed values for local hypersoftnes are well-separated: 4-meloxicam, lornoxicam, meloxicam, and normeloxicam. Meanwhile, the opposite situation is found in droxicam, isoxicam, piroxicam, and tenoxicam. As a whole, the nucleophilic characteristic noticeably predominates in these eight oxicams instead of an electrophilic behavior, thus meaning a greater tendency to donate electrons rather than withdrawing them; a consequence of this behavior implies a favorable interaction with a hypothetical receptor bearing one or more electron acceptor functional groups rather than electron donor functional groups; this would imply a maximization of this interaction from the covalent point of view.

  14. Quantitation of meloxicam in the plasma of koalas (Phascolarctos cinereus) by improved high performance liquid chromatography.

    Science.gov (United States)

    Kimble, Benjamin; Li, Kong Ming; Govendir, Merran

    2013-01-01

    An improved method to determine meloxicam (MEL) concentrations in koala plasma using reversed phase high performance liquid chromatography equipped with a photo diode array detector was developed and validated. A plasma sample clean-up step was carried out with hydrophilic- lipophilic copolymer solid phase extraction cartridges. MEL was separated from an endogenous interference using an isocratic mobile phase [acetonitrile and 50 mM potassium phosphate buffer (pH 2.15), 45 : 55 (v : v)] on a Nova-Pak C18 4-µm (300 × 3.9 mm) column. Retention times for MEL and piroxicam were 8.03 and 5.56 min, respectively. Peak area ratios of MEL to the internal standard (IS) were used for regression analysis of the calibration curve, which was linear from 10 to 1,000 ng/mL (r(2) > 0.9998). Average absolute recovery rates were 91% and 96% for MEL and the IS, respectively. This method had sufficient sensitivity (lower quantitation limit of 10 ng/mL), precision, accuracy, and selectivity for routine analysis of MEL in koala plasma using 250-µL sample volumes. Our technique clearly resolved the MEL peak from the complex koala plasma matrix and accurately measured MEL concentrations in small plasma volumes.

  15. In vitro antioxidant and cell viability of Pyrostegia venusta (Ker Gawl. Miers

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    Thales D. P. Altoé

    2015-01-01

    Full Text Available Many diseases are associated with oxidative stress and inflammatory processes. The current research is directed toward evaluating the antioxidant potential and phytochemistry composition of P. venusta leaves. In this study, P. venusta leaves were dried and macerated, and the crude extract was partitioned. Phytochemical analysis was performed using standard methodologies, and the total flavonoid content was measured using a calibration curve with rutin. We evaluated the antioxidant potential of P. venusta leaves using 1,1-Diphenyl-2-picrylhydrazyl (DPPH, 2, 2’-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS, and a Trolox-like standard. Cell viability (CV assays were done using macrophage RAW 264.7 cell lines and compared to four commercial anti-inflammatories (acetylsalicylic acid, Indometacina, Betametasona, and Piroxicam. Phytochemical analysis revealed the presence of steroids, coumarins, and flavone. The flavonoid content was 148.5 ± 7.65 µg as a rutin equivalent/mg of crude extract. The ethyl acetate fraction showed the best antioxidant activity in the methodologies of DPPH inhibition (IC50 = 38.62 µg/mL and ABTS radical (IC50 = 28.58 µg/mL. Samples of P. venusta had CV values that were better than the commercial anti-inflammatory, which showed CV values below the negative control. The crude extract and the ethyl acetate fraction, showed CV values below the negative control and the hexane fraction obtained values above the negative control, these being best results.

  16. Adsorptive removal of pharmaceuticals from water by commercial and waste-based carbons.

    Science.gov (United States)

    Calisto, Vânia; Ferreira, Catarina I A; Oliveira, João A B P; Otero, Marta; Esteves, Valdemar I

    2015-04-01

    This work describes the single adsorption of seven pharmaceuticals (carbamazepine, oxazepam, sulfamethoxazole, piroxicam, cetirizine, venlafaxine and paroxetine) from water onto a commercially available activated carbon and a non-activated carbon produced by pyrolysis of primary paper mill sludge. Kinetics and equilibrium adsorption studies were performed using a batch experimental approach. For all pharmaceuticals, both carbons presented fast kinetics (equilibrium times varying from less than 5 min to 120 min), mainly described by a pseudo-second order model. Equilibrium data were appropriately described by the Langmuir and Freundlich isotherm models, the last one giving slightly higher correlation coefficients. The fitted parameters obtained for both models were quite different for the seven pharmaceuticals under study. In order to evaluate the influence of water solubility, log Kow, pKa, polar surface area and number of hydrogen bond acceptors of pharmaceuticals on the adsorption parameters, multiple linear regression analysis was performed. The variability is mainly due to log Kow followed by water solubility, in the case of the waste-based carbon, and due to water solubility in the case of the commercial activated carbon.

  17. Concentration of Non-Steroidal Anti-Inflammatory Drugs in the Pelvic Floor Muscles: An Experimental Comparative Rat Model

    Science.gov (United States)

    Chin, Hung-Yen; Changchien, Eileen; Lin, Mei-Fung; Chiang, Chi-Hsin

    2014-01-01

    Purpose The aim of this study is to explore non-steroid anti-inflammation drugs (NSAIDs) potency for pelvic floor muscle pain by measuring local concentration in a rat model. Materials and Methods We used nine NSAIDs, including nabumetone, naproxen, ibuprofen, meloxicam, piroxicam, diclofenac potassium, etodolac, indomethacin, and sulindac, and 9 groups of female Wister rats. Each group of rats was fed with one kind of NSAID (2 mg/mL) for three consecutive days. Thereafter, one mL of blood and one gram of pelvic floor muscle were taken to measure drug pharmacokinetics, including partition coefficient, lipophilicity, elimination of half-life (T1/2) and muscle/plasma converting ratio (Css, muscle/Css, plasma). Results Diclofenac potassium had the lowest T1/2 and the highest mean Css, muscle/Css, plasma (1.9 hours and 0.85±0.53, respectively). The mean Css, muscle/Css, plasma of sulindac, naproxen and ibuprofen were lower than other experimental NSAIDs. Conclusion Diclofenac potassium had the highest disposition in pelvic floor muscle in a rat model. The finding implies that diclofenac potassium might be the choice for pain relief in pelvic muscle. PMID:24954342

  18. Compaction properties of crystalline pharmaceutical ingredients according to the Walker model and nanomechanical attributes.

    Science.gov (United States)

    Egart, M; Ilić, I; Janković, B; Lah, N; Srčič, S

    2014-09-10

    This study investigates the extent to which single-crystal mechanical properties of selected active ingredients (famotidine, nifedipine, olanzapine, piroxicam) influence their bulk compressibility and compactibility. Nanomechanical attributes of oriented single crystals were determined with instrumented nanoindentation, and bulk deformational properties were assessed with the Walker and Heckel models as well as the elastic relaxation index. Good correlations were established between bulk and single-crystal plasticity parameters: the Walker coefficient and indentation hardness. The Walker model showed more practical value for evaluating bulk deformational properties of the APIs investigated because their properties differed more distinctly compared to the Heckel model. In addition, it was possible to predict the elastic properties of the materials investigated at the bulk level because a correlation between the elastic relaxation index and compliance was established. The value of using indentation hardness for crystalline APIs was also confirmed because their compactibility at the bulk level was able to be predicted. Mechanically interlocked structures were characteristic of most polymorphic forms investigated, resulting in single crystals having isotropic mechanical properties. It was revealed that in such cases good correlations between single and bulk mechanical properties can be expected. The results imply that innate crystal deformational properties define their compressibility and compactibility properties to a great extent. Copyright © 2014. Published by Elsevier B.V.

  19. Nanomechanical properties of selected single pharmaceutical crystals as a predictor of their bulk behaviour.

    Science.gov (United States)

    Egart, Mateja; Janković, Biljana; Lah, Nina; Ilić, Ilija; Srčič, Stanko

    2015-02-01

    The main goal of this research was to assess the mechanical properties of APIs' polymorphic forms at the single-crystal level (piroxicam, famotidine, nifedipine, olanzapine) in order to predict their bulk deformational attributes, which are critical for some pharmaceutical technology processes. The mechanical properties of oriented single crystals were determined using instrumented nanoindentation (continuous stiffness measurement). All polymorphic forms investigated were previously identified using a combination of calorimetric and spectroscopic techniques. Mechanical properties such as Young's modulus and indentation hardness were consistent with the molecular packing of the polymorphic forms investigated with respect to crystal orientation. For mechanically interlocked structures, characteristic of most polymorphic forms, response of single crystals to indentation was isotropic. The material's bulk elastic properties can be successfully predicted by measuring Young's modulus of single crystals because a good linear correlation with a bulk parameter such as the tablets' elastic relaxation index was determined. The results confirm the idea that the intrinsic mechanical properties of pharmaceutical crystals (Young's modulus) largely control and anticipate their deformational behavior during tablet compression. Young's modulus and indentation hardness represent a very valuable and effective tool in preformulation studies for describing materials' mechanical attributes, which are important for technological processes in which materials are exposed to deformation.

  20. Use of diffusion-ordered NMR spectroscopy and HPLC-UV-SPE-NMR to identify undeclared synthetic drugs in medicines illegally sold as phytotherapies.

    Science.gov (United States)

    Silva, Lorena M A; Filho, Elenilson G A; Thomasi, Sérgio S; Silva, Bianca F; Ferreira, Antonio G; Venâncio, Tiago

    2013-09-01

    The informal (and/or illegal) e-commerce of pharmaceutical formulations causes problems that governmental health agencies find hard to control, one of which concerns formulas sold as natural products. The purpose of this work was to explore the advantages and limitations of DOSY and HPLC-UV-SPE-NMR. These techniques were used to identify the components of a formula illegally marketed in Brazil as an herbal medicine possessing anti-inflammatory and analgesic properties. DOSY was able to detect the major components present at higher concentrations. Complete characterization was achieved using HPLC-UV-SPE-NMR, and 1D and 2D NMR analyses enabled the identification of known synthetic drugs. These were ranitidine and a mixture of orphenadrine citrate, piroxicam, and dexamethasone, which are co-formulated in a remedy called Rheumazim that is used to relieve severe pain, but it is prohibited in Brazil because of a lack of sufficient pharmacokinetic and pharmacodynamic information. Copyright © 2013 John Wiley & Sons, Ltd.

  1. Applying a novel electrostatic dry powder coating technology to pellets.

    Science.gov (United States)

    Yang, Qingliang; Ma, Yingliang; Zhu, Jesse

    2015-11-01

    The present study aimed to apply a novel dry powder technology to coat pellets with different coating materials grounded into fine powders. Piroxicam, a non-steroidal anti-inflammatory drug, was used as the active pharmaceutical ingredient (API). Eudragit® EPO, Eudragit® RS/RL and Acryl EZE were used as the coating materials to achieve immediate release, sustained release and delayed release, respectively. Three steps including preheating, powder adhesion and curing were carried out to form the coating film while liquid plasticizers were used to decrease the glass transition temperature of coating powders and also served to reduce the electrical resistance of pellets. Results of SEM indicated coating film could be better formed by increasing curing temperature or extending curing time. Dissolution tests showed that three different drug release profiles, including immediate release, sustained release and delayed release, were achieved by this coating technology with different coating formulations. And the dry powder coated pellets using this developed technology exhibited an excellent stability with 1 month at 40 °C/75% RH. The coating procedure could be shortened to within 120 min and the use of fluidized hot air was minimized, both cutting down the overall cost dramatically compared to organic solvent coating and aqueous coating. All results demonstrated that the novel electrostatic dry powder coating method is a promising technology in the pharmaceutical coating industry.

  2. Soluplus Graft Copolymer: Potential Novel Carrier Polymer in Electrospinning of Nanofibrous Drug Delivery Systems for Wound Therapy

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    Urve Paaver

    2014-01-01

    Full Text Available Electrospinning is an effective method in preparing polymeric nanofibrous drug delivery systems (DDSs for topical wound healing and skin burn therapy applications. The aim of the present study was to investigate a new synthetic graft copolymer (Soluplus as a hydrophilic carrier polymer in electrospinning of nanofibrous DDSs. Soluplus (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PCL-PVAc-PEG was applied in the nonwoven nanomats loaded with piroxicam (PRX as a poorly water-soluble drug. Raman spectroscopy, X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy (SEM were used in the physical characterization of nanofibrous DDSs. According to the SEM results, the drug-loaded PCL-PVAc-PEG nanofibers were circular in cross-section with an average diameter ranging from 500 nm up to 2 µm. Electrospinning stabilized the amorphous state of PRX. In addition, consistent and sustained-release profile was achieved with the present nanofibrous DDSs at the physiologically relevant temperature and pH applicable in wound healing therapy. In conclusion, electrospinning can be used to prepare nanofibrous DDSs of PCL-PVAc-PEG graft copolymer (Soluplus and to stabilize the amorphous state of a poorly water-soluble PRX. The use of this synthetic graft copolymer can open new options to formulate nanofibrous DDSs for wound healing.

  3. Effect of Cyclodextrin Types and Co-Solvent on Solubility of a Poorly Water Soluble Drug

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    Suporn Charumanee

    2016-10-01

    Full Text Available The aim of the study was to investigate the solubility of piroxicam (Prx depending on the inclusion complexation with various cyclodextrins (CDs and on ethanol as a co-solvent. The phase-solubility method was applied to determine drug solubility in binary and ternary systems. The results showed that in systems consisting of the drug dissolved in ethanol–water mixtures, the drug solubility increased exponentially with a rising concentration of ethanol. The phase solubility measurements of the drug in aqueous solutions of CDs, β-CD and γ-CD exhibited diagrams of AL-type, whereas 2,6-dimethyl-β-CD revealed AP-type. The destabilizing effect of ethanol as a co-solvent was observed for all complexes regardless of the CD type, as a consequence of it the lowering of the complex formation constants. In systems with a higher concentration of ethanol, the drug solubility was increased in opposition to the decreasing complex formation constants. According to this study, the type of CDs played a more important role on the solubility of Prx, and the use of ethanol as a co-solvent exhibited no synergistic effect on the improvement of Prx solubility. The Prx solubility was increased again due to the better solubility in ethanol.

  4. Alkylglycerol Derivatives, a New Class of Skin Penetration Modulators

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    Sergio Alberto Bernal-Chávez

    2017-01-01

    Full Text Available The absorption modulating activity of two alkylglycerol derivatives (batyl and chimyl alcohol on skin barrier properties was evaluated. Biophysical tests such as transepidermal water loss (TEWL and attenuated total reflectance–Fourier transform infrared (ATR-FTIR spectroscopy, as well as in vitro skin permeation studies, were performed in order to determine the effect of these compounds as chemical absorption modulators. Four drugs were used as models: three NSAIDS (diclofenac, naproxen, and piroxicam and glycyrrhizic acid. The results showed that treatment of the skin with alkylglycerols caused (i a reduction on the amount of drug permeated; (ii a reduction in TEWL; and (iii changes in the ATR-FTIR peaks of stratum corneum lipids, indicative of a more ordered structure. All of these findings confirm that alkyl glycerols have an absorption retarding effect on the drugs tested. Such effects are expected to give rise to important applications in the pharmaceutical and cosmetic sectors, in cases where it is desirable for the drug to remain in the superficial layers of the skin to achieve a local effect.

  5. Perbedaan Tolerabilitas Meloxicam dengan Natrium Diklofenak terhadap Saluran Cerna pada Pasien Rawat Jalan di PoliklinikPenyakit Saraf Rumah Sakit Angkatan Laut Dr. Mintohardjo Jakarta 2011

    Directory of Open Access Journals (Sweden)

    Lailan Azizah

    2013-06-01

    Full Text Available Abstrak Obat anti inflamasi non steroid dihubungkan dengan insiden efek samping yang tinggi terhadap saluran cerna. Penghambatan enzim siklooksigenase merupakan dasar efikasi dan toksisitas obat anti inflamasi non steroid. Penelitian ini bertujuan untuk mengevaluasi jenis obat anti inflamasi non steroid yang digunakan di poliklinik penyakit saraf Rumah Sakit Angkatan Laut (Rumkital Dr. Mintohardjo Jakarta dan mengevaluasi tolerabilitas meloxicam 15 mg dengan natrium diklofenak 100 mg terhadap saluran cerna. Metode penelitian ini observasi cross-sectional dan cohortprospektif pada periode Desember 2010–Maret 2011. Pengambilan data mengenai keluhan dispepsia terkait penggunaan obat anti inflamasi non steroid terdiri dari nyeri abdomen atas, mual, muntah, kembung abdomen, dan cepat kenyang dilakukan melalui wawancara berdasarkan kuesioner the porto alegre dyspeptic symptoms questionnaire (PADYQyaitu sebelum, setelah 2 minggu, dan setelah 4 minggu pengobatan. Hasil penelitian menyatakan obat anti inflamasi non steroid paling banyak diresepkan di poliklinik penyakit saraf Rumkital Dr. Mintohardjo adalah meloxicam (48,21%, selanjutnya natrium diklofenak (31,07%, asam mefenamat (15,36%, piroxicam (3,93% dan asetaminofen (1,43%. Meloxicam secara bermakna menunjukkan risiko yang lebih kecil terhadap insiden saluran cerna daripada natrium diklofenak setelah 2 minggu pengobatan dalam hal keluhan nyeri abdomen atas dan kembung abdomen dengannilai kebermaknaan pengujian masing-masing sebesar 0,020 dan 0,037. Berdasarkan hasil penelitian ini diketahui meloxicam memiliki tolerabilitas saluran cerna lebih baik daripada natrium diklofenak setelah 2 minggu pengobatan. AbstractPerbedaan Tolerabilitas Meloxicam dengan Natrium Diklofenak terhadap Saluran Cerna pada Pasien Rawat Jalan di Poliklinik Penyakit Saraf Rumah Sakit Angkatan Laut Dr. Mintohardjo, Jakarta 2011. Non-steroidal anti-inflammatory drugs (NSAIDs are associated with a high incidence of

  6. Cuantificación de glibenclamida en muestras de limpieza de equipos farmacéuticos mediante cromatografía líquida de alta resolución Quantification of glibenclamide in cleaning samples of pharmaceutical equipment through high performance liquid chromatography

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    Alen Nils Baeza Fonte

    2012-03-01

    Full Text Available Objetivo: proponer un procedimiento analítico selectivo para la cuantificación de glibenclamida en muestras de limpieza de equipos farmacéuticos mediante cromatografía líquida de alta resolución. Métodos: la fase móvil consistió en una mezcla equivalente de volúmenes de acetonitrilo y solución amortiguadora KH2PO4 de concentración 0,037 mol/L a pH 5,25 y flujo 1,5 mL/min, en una columna Nucleosil 100 C8. La glibenclamida se inyectó con progesterona como estándar interno y empleando detector UV a una l= 230 nm. Resultados: el método resultó lineal en el intervalo de concentraciones de 0,4-150 mg/mL, teniendo como límites de detección y cuantificación 10 y 40 ng/mL respectivamente y siendo específico al analito en presencia del placebo, sus productos de degradación y a otros ingredientes farmacéuticamente activos. Se consideraron potenciales de interferencias para el método propuesto: captopril, clortalidona, dexametasona, digoxina, 8-cloroteofilina, difenhidramina HCl, fenobarbital, haloperidol, hidroclorotiazida, ácido fumárico, ketotifeno, metoclopramida HCl, piridoxina HCl, piroxicam, prednisona y nifedipino. Se identificaron: ibuprofeno, indometacina, trifluoperazina HCl, tioridazina HCl e imipramina HCl, como interferentes del procedimiento en concentraciones cercanas a 10 mg/mL. Conclusiones: el método desarrollado es sensible, rápido y especialmente selectivo para la evaluación de residuales del principio activo glibenclamida en equipos de producción de tabletas, empleando un muestreo por hisopado, y pudiera utilizarse potencialmente cuando exista sospecha de contaminación cruzada de glibenclamida con otros fármacos de los aquí descritos.Objective: to submit a selective analytical method for quantization of glibenclamide in cleaning samples of pharmaceutical equipment using high performance liquid chromatography. Methods: the mobile phase consisted of an equal mixing of acetonitrile/phosphate buffer KH2PO4

  7. Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes.

    Science.gov (United States)

    Nadanaciva, Sashi; Aleo, Michael D; Strock, Christopher J; Stedman, Donald B; Wang, Huijun; Will, Yvonne

    2013-10-15

    To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify "toxic" and "non-toxic" drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition.

  8. Antinociceptive synergy, additivity, and subadditivity with combinations of oral glucosamine plus nonopioid analgesics in mice.

    Science.gov (United States)

    Tallarida, Ronald J; Cowan, Alan; Raffa, Robert B

    2003-11-01

    Glucosamine (2-amino-2-deoxy-d-glucose) and glucosamine-containing products have been reported to have efficacy in the treatment of various musculoskeletal disorders. Glucosamine's efficacy, including reduction of pain, is attributed to disease-modifying properties, specifically to cartilage-rebuilding associated with modulation of interleukin-1-induced activation of chondrocytes and to inhibition of proinflammatory effects of the nuclear factor-kappaB pathway. However, glucosamine has not been shown to have direct analgesic activity. We report here that commercial glucosamine (90.4% glucosamine sulfate + 9.6% excipients) administered as the sole agent (up to 500 mg/kg p.o.) was inactive in the mouse abdominal irritant test but that certain combinations of glucosamine with nonopioid analgesics at the oral doses and ratios tested resulted in a synergistic (ibuprofen and ketoprofen), additive (diclofenac, indomethacin, naproxen, and piroxicam), or subadditive (aspirin and acetaminophen) antinociceptive interaction. In the specific case of ibuprofen, the racemate (standard ibuprofen) produced dose-related antinociception with ED50 = 26.1 +/- 3.4 mg/kg. Combinations containing racemic ibuprofen and glucosamine in greater than 1:1 ratio (glucosamine/ibuprofen) were synergistic in the test (e.g., ED50 = 11.0 +/- 2.1 for the 9:1 ratio; p < 0.01, analysis of variance). Combinations containing glucosamine and ibuprofen (2:1 and 9:1) yielded plasma levels of ibuprofen that were no different from administration of ibuprofen alone. The possibility that combinations containing certain fixed ratios of glucosamine and certain nonsteroidal anti-inflammatory drugs (NSAIDs) might enhance pain relief in patients with pain or might achieve acceptable levels of pain relief with lower doses of NSAIDs (reduced adverse effects) is presently being pursued in clinical trials.

  9. Differential expression of thromboxane synthase in prostate carcinoma: role in tumor cell motility.

    Science.gov (United States)

    Nie, Daotai; Che, Mingxin; Zacharek, Alex; Qiao, Yan; Li, Li; Li, Xinglin; Lamberti, Mario; Tang, Keqin; Cai, Yilong; Guo, Yande; Grignon, David; Honn, Kenneth V

    2004-02-01

    Arachidonic acid metabolism through cyclooxygenase, lipoxygenase, or P-450 epoxygenase pathways can generate a variety of eicosanoids. Thromboxane synthase (TxS) metabolizes the cyclooxygenase product, prostanglandin H(2), into thromboxane A(2) (TXA(2)), which can cause vessel constriction, platelet activation, and aggregation. Here we demonstrate that human prostate cancer (PCa) cells express enzymatically active TxS and that this enzyme is involved in cell motility. In human PCa cell lines, PC-3, PC-3M, and ML-2 cells expressed higher levels of TxS than normal prostate epithelial cells or other established PCa cell lines such as DU145, LNCaP, or PPC-1. We cloned and sequenced the full-length TxS cDNA from PC-3 cells and found two changes in the amino acid residues. Immunohistochemical analysis of tumor specimens revealed that expression of TxS is weak or absent in normal differentiated luminal, or secretory cells, significantly elevated in less differentiated or advanced prostate tumors, and markedly increased in tumors with perineural invasion. TxS expressed in PC-3 cells was enzymatically active and susceptible to carboxyheptal imidazole, an inhibitor of TxS. The biosynthesis of TXA(2) in PC-3 cells was dependent on COX-2, and to a lesser extent, COX-1. Treatment of PC-3 cells with a COX-1 selective inhibitor, piroxicam, reduced TXA(2) synthesis by approximately 40%, while the COX-2 specific inhibitor NS398 reduced TXA(2) production by approximately 80%. Inhibition of TxS activity or blockade of TXA(2) function reduced PC-3 cell migration on fibronectin, while having minimal effects on cell cycle progression or survival. Finally, increased expression of TxS in DU145 cells increased cell motility. Our data suggest that human PCa cells express TxS and that this enzyme may contribute to PCa progression through modulating cell motility.

  10. Cost-effectiveness analysis for joint pain treatment in patients with osteoarthritis treated at the Instituto Mexicano del Seguro Social (IMSS): Comparison of nonsteroidal anti-inflammatory drugs (NSAIDs) vs. cyclooxygenase-2 selective inhibitors.

    Science.gov (United States)

    Contreras-Hernández, Iris; Mould-Quevedo, Joaquín F; Torres-González, Rubén; Goycochea-Robles, María Victoria; Pacheco-Domínguez, Reyna Lizette; Sánchez-García, Sergio; Mejía-Aranguré, Juan Manuel; Garduño-Espinosa, Juan

    2008-11-12

    Osteoarthritis (OA) is one of the main causes of disability worldwide, especially in persons >55 years of age. Currently, controversy remains about the best therapeutic alternative for this disease when evaluated from a cost-effectiveness viewpoint. For Social Security Institutions in developing countries, it is very important to assess what drugs may decrease the subsequent use of medical care resources, considering their adverse events that are known to have a significant increase in medical care costs of patients with OA. Three treatment alternatives were compared: celecoxib (200 mg twice daily), non-selective NSAIDs (naproxen, 500 mg twice daily; diclofenac, 100 mg twice daily; and piroxicam, 20 mg/day) and acetaminophen, 1000 mg twice daily. The aim of this study was to identify the most cost-effective first-choice pharmacological treatment for the control of joint pain secondary to OA in patients treated at the Instituto Mexicano del Seguro Social (IMSS). A cost-effectiveness assessment was carried out. A systematic review of the literature was performed to obtain transition probabilities. In order to evaluate analysis robustness, one-way and probabilistic sensitivity analyses were conducted. Estimations were done for a 6-month period. Treatment demonstrating the best cost-effectiveness results [lowest cost-effectiveness ratio $17.5 pesos/patient ($1.75 USD)] was celecoxib. According to the one-way sensitivity analysis, celecoxib would need to markedly decrease its effectiveness in order for it to not be the optimal treatment option. In the probabilistic analysis, both in the construction of the acceptability curves and in the estimation of net economic benefits, the most cost-effective option was celecoxib. From a Mexican institutional perspective and probably in other Social Security Institutions in similar developing countries, the most cost-effective option for treatment of knee and/or hip OA would be celecoxib.

  11. Intra-hippocampal injection of lipopolysaccharide inhibits kindled seizures and retards kindling rate in adult rats.

    Science.gov (United States)

    Ahmadi, Amin; Sayyah, Mohammad; Khoshkholgh-Sima, Baharak; Choopani, Samira; Kazemi, Jafar; Sadegh, Mehdi; Moradpour, Farshad; Nahrevanian, Hossein

    2013-04-01

    Neuroinflammation facilitates seizure acquisition and epileptogenesis in developing brain. Yet, the studies on impact of neuroinflammation on mature brain epileptogenesis have led to inconsistent results. Hippocampus is particularly vulnerable to damage caused by ischemia, hypoxia and trauma, and the consequent neuroinflammation, which can lead in turn to epilepsy. Lipopolysaccharide (LPS) is extensively used in experimental studies to induce neuroinflammation. In this study, effect of acute and chronic intra-CA1 infusion of LPS on amygdala-kindled seizures and epileptogenesis was examined in mature rats. LPS (5 μg/rat) inhibited evoked amygdala afterdischarges and behavioral seizures. Anticonvulsant effect of LPS was observed 0.5 h after administration and continued up to 24 h. This effect was accompanied by intra-hippocampal elevation of nitric oxide (NO), interleukin1-β, and tumor necrosis factor-α and was prevented by microglia inhibitor, naloxone, NO synthase inhibitor, Nω-nitro-L-arginine methyl ester, cyclooxygenase inhibitor, piroxicam, and interleukin1-β receptor antagonist, interleukin1-ra. Moreover, daily intra-hippocampal injection of LPS significantly retarded kindling rate. In order to further elucidate the effect of LPS on synaptic transmission and short-term plasticity, changes in field excitatory postsynaptic potentials and population spikes were measured in stratum radiatum and stratum pyramidale of LPS-treated kindled rats. LPS impaired baseline synaptic transmission in hippocampal Schaffer collateral-CA1 synapse and reduced the magnitude of paired-pulse facilitation. Our results suggest that direct suppression of presynaptic mechanisms in Schaffer collateral-CA1 synapses, as well as the inflammatory mediators released by LPS in the hippocampus, is involved in antiepileptic effect of LPS.

  12. Blockade of the renin-angiotensin system prevents acute and immunologically relevant colitis in murine models.

    Science.gov (United States)

    Okawada, Manabu; Wilson, Michael W; Larsen, Scott D; Lipka, Elke; Hillfinger, John; Teitelbaum, Daniel H

    2016-12-01

    Blockade of the renin-angiotensin system (RAS) has been shown to alleviate inflammatory processes in the gastrointestinal tract. The aim of this study was to determine if blockade of the RAS would be effective in an immunologically relevant colitis model, and to compare outcome with an acute colitis model. A losartan analog, CCG-203025 (C23H26ClN3O5S) containing a highly polar sulfonic acid moiety that we expected would allow localized mucosal antagonism with minimal systemic absorption was selected as an angiotensin II type 1a receptor antagonist (AT1aR-A). Two colitis models were studied: (1) Acute colitis was induced in 8- to 10-week-old C57BL/6J mice by 2.5 % dextran sodium sulfate (DSS, in drinking water) for 7 days. (2) IL10-/-colitis Piroxicam (200 ppm) was administered orally in feed to 5-week-old IL-10-/-mice (C57BL/6J background) for 14 days followed by enalaprilat (ACE-I), CCG-203025 or PBS administered transanally for 14 days. In the DSS model, weight loss and histologic score for CCG-203025 were better than with placebo. In the IL10-/-model, ACE-I suppressed histologic damage better than CCG-203025. Both ACE-I and CCG-203025 reduced pro-inflammatory cytokines and chemokines. This study demonstrated the therapeutic efficacy of both ACE-I and AT1aR-A for preventing the development of both acute and immunologically relevant colitis.

  13. Efeito do meloxicam sobre a lesão de isquemia e reperfusão em músculo esquelético de ratos Effect of meloxicam on ischemia-reperfusion injury in skeletal muscle of rats

    Directory of Open Access Journals (Sweden)

    Vitor A. Uhle

    2000-01-01

    Full Text Available Os antiinflamatórios não esteroidais, derivados do piroxicam, agem como varredores de radicais livres de oxigênio em experimentos in vitro. O objetivo deste trabalho foi analisar o efeito do meloxicam em músculos esqueléticos de ratos submetidos à isquemia e reperfusão com base na análise de liberação de malondialdeído da membrana celular ( indicador de peroxidação lipídica provocada pelos radicais livres. Dezoito ratos Wistar foram divididos em 2 grupos de 9. O grupo I (grupo sham foi tratado previamente com 3g/kg de peso de solução fisiológica e o grupo II com 3g/kg de peso de meloxicam por via peritoneal. Após 5 min os ratos foram submetidos a 3h de isquemia total ( torniquete e 45 min de reperfusão das patas posteriores esquerdas. Colheram-se biópsias dos músculos isquêmicos e reperfundidos e das patas controles (contralaterais para a dosagem de malondialdeído. A análise das diferenças de concentração do malondiadeído nas patas controles e reperfundidas no grupo I (43,7± 60,7; n=9 em relação ao grupo II (21,7± 49,5; n=9 não mostrou alteração significante (p=0,3. Os dados obtidos, neste trabalho, mostram que o meloxicam não protege a musculatura esquelética dos danos causados pela isquemia e reperfusão, com base na análise do malondialdeído tissular após 3h de isquemia e 45 min de reperfusão.

  14. Differential stimulation of luminol-enhanced chemiluminescence (CL) and arachidonic acid metabolism in rat peritoneal neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Sturm, R.J.; Adams, L.M.; Cullinan, C.A.; Berkenkopf, J.W.; Weichman, B.M.

    1986-03-05

    Phorbol 12-myristate, 13-acetate (PMA) induced the production of radical oxygen species (ROS) from rat peritoneal neutrophils as assessed by CL. ROS generation occurred in a time- (maximum at 13.5 min) and dose- (concentration range of 1.7-498 nM) related fashion. However, 166 nM PMA did not induce either cyclooxygenase (CO) or lipoxygenase (LPO) product formation by 20 min post-stimulation. Conversely, A23187, at concentrations between 0.1 and 10 ..mu..M, stimulated both pathways of arachidonic acid metabolism, but had little or no effect upon ROS production. When suboptimal concentrations of PMA (5.5 nM) and A23187 (0.1-1 ..mu..M) were coincubated with the neutrophils, a synergistic ROS response was elicited. However, arachidonic acid metabolism in the presence of PMA was unchanged relative to A12187 alone. Nordihydroguaiaretic acid (NDGA) inhibited both PMA-induced CL (IC/sub 50/ = 0.9 ..mu..M) and A23187-induced arachidonic acid metabolism (IC/sub 50/ = 1.7 ..mu..M and 6.0 ..mu..M for LPO and CO, respectively). The mixed LPO-CO inhibitor, BW755C, behaved in a qualitatively similar manner to NDGA, whereas the CO inhibitors, indomethacin, piroxicam and naproxen had no inhibitory effect on ROS generation at concentrations as high as 100 ..mu..M. These results suggest that NDGA and BW755C may inhibit CL and arachidonic acid metabolism by distinct mechanisms in rat neutrophils.

  15. Cost-effectiveness analysis for joint pain treatment in patients with osteoarthritis treated at the Instituto Mexicano del Seguro Social (IMSS: Comparison of nonsteroidal anti-inflammatory drugs (NSAIDs vs. cyclooxygenase-2 selective inhibitors

    Directory of Open Access Journals (Sweden)

    Mejía-Aranguré Juan

    2008-11-01

    Full Text Available Abstract Background Osteoarthritis (OA is one of the main causes of disability worldwide, especially in persons >55 years of age. Currently, controversy remains about the best therapeutic alternative for this disease when evaluated from a cost-effectiveness viewpoint. For Social Security Institutions in developing countries, it is very important to assess what drugs may decrease the subsequent use of medical care resources, considering their adverse events that are known to have a significant increase in medical care costs of patients with OA. Three treatment alternatives were compared: celecoxib (200 mg twice daily, non-selective NSAIDs (naproxen, 500 mg twice daily; diclofenac, 100 mg twice daily; and piroxicam, 20 mg/day and acetaminophen, 1000 mg twice daily. The aim of this study was to identify the most cost-effective first-choice pharmacological treatment for the control of joint pain secondary to OA in patients treated at the Instituto Mexicano del Seguro Social (IMSS. Methods A cost-effectiveness assessment was carried out. A systematic review of the literature was performed to obtain transition probabilities. In order to evaluate analysis robustness, one-way and probabilistic sensitivity analyses were conducted. Estimations were done for a 6-month period. Results Treatment demonstrating the best cost-effectiveness results [lowest cost-effectiveness ratio $17.5 pesos/patient ($1.75 USD] was celecoxib. According to the one-way sensitivity analysis, celecoxib would need to markedly decrease its effectiveness in order for it to not be the optimal treatment option. In the probabilistic analysis, both in the construction of the acceptability curves and in the estimation of net economic benefits, the most cost-effective option was celecoxib. Conclusion From a Mexican institutional perspective and probably in other Social Security Institutions in similar developing countries, the most cost-effective option for treatment of knee and/or hip OA

  16. Calcium-dependent synergistic interaction of platelet activating factor and epinephrine in human platelet aggregation%血小板活化因子和肾上腺素对人血小板凝集的钙依赖性协同作用

    Institute of Scientific and Technical Information of China (English)

    Sheikh Arshad SAEED; Huma RASHEED

    2003-01-01

    AIM: To investigate the mechanism (s) involved in the synergistic interaction of platelet activating factor (PAF) and epinephrine. METHODS: Blood was obtained from healthy human subjects reported to be free of medications for at least two weeks before sampling. Aggregation was monitored at 37 ℃ using Dual-channel Lumi-aggregometer.The resulting aggregation was recorded for 5 min by the measurement of light transmission as a function of time.RESULTS: Platelet aggregation mediated by subthreshold concentrations of PAF (5-8 nmol/L) plus epinephrine (0.5-2 μmol/L) was inhibited by α2-receptor blocker, yohimbine, and PAF receptor antagonist WEB 2086. This synergism was inhibited by calcium channel blockers, verapamil and diltiazem. In addition, platelet aggregation by co-addition of PAF and epinephrine was also inhibited by very low concentrations of phospholipase C (PLC)inhibitor (U73122; IC50=0.2 μmol/L), the MAP kinase inhibitor, PD 98059 (IC50=3 μmol/L), and cyclooxygenase (COX-1) inhibitors including indomethacin (IC50=0.25 μmol/L), flurbiprofen (IC50=0.7 μmol/L), and piroxicam (IC50=7 μmol/L). However, COX-2 inhibitors, nimesulide (IC50=26 μmol/L), NS-398 (IC50=7 μmol/L), and etodolac (IC50=15 μmol/L) were also effective in inhibiting the aggregation. The inhibitors of protein kinase C (chelerythrine)and tyrosine kinase (genistien), and phosphatidylinositol 3-kinase inhibitor (wortmannin) had no significant effect on platelet aggregation induced by PAF and epinephrine. CONCLUSION: The synergistic effect of PAF and epinephrine on human platelet aggregation is receptor-mediated and involves the activation of PLC/Ca2+, COX and MAP kinase signalling pathways.

  17. HPLC法测定吡罗昔康注射液的含量

    Institute of Scientific and Technical Information of China (English)

    曹玲; 唐树荣; 万嵘

    2001-01-01

    @@ 吡罗昔康(piroxicam),又名炎痛喜康,是一种非甾体类抗炎药物,具有明显的解热、镇痛、抗炎作用,在国外已得到广泛的应用,为中国药典1995年版[1]新增品种,由于其注射液处方组成复杂,中国药典采用氯仿多次提取处理后,再用非水法测定含量。该法操作繁琐费时,采用大量有害的有机溶剂,并且容易带来人为误差。本文参考有关文献[2,3],采用反相高效液相色谱法(外标法),直接测定吡罗昔康注射液的含量,方法简便、快捷,专属性强,灵敏度高,结果准确可靠。 1 仪器与试药 岛津LC-10AD高效液相色谱恒流泵;SPD-10A紫外检测仪;C-R 6A数据处理机;20 μL定量进样器。 吡罗昔康对照品(中国药品生物制品检定所);吡罗昔康注射液(无锡华裕制药有限公司,规格为2 mL:20 mg);所用试剂均为AR级。

  18. Fractional derivatives in the transport of drugs across biological materials and human skin

    Science.gov (United States)

    Caputo, Michele; Cametti, Cesare

    2016-11-01

    The diffusion of drugs across a composite structure such as a biological membrane is a rather complex phenomenon, because of its inhomogeneous nature, yielding a diffusion rate and a drug solubility strongly dependent on the local position across the membrane itself. These problems are particularly strengthened in composite structures of a considerable thickness like, for example, the human skin, where the high heterogeneity provokes the transport through different simultaneous pathways. In this note, we propose a generalization of the diffusion model based on Fick's 2nd equation by substituting a diffusion constant by means of the memory formalism approach (diffusion with memory). In particular, we employ two different definitions of the fractional derivative, i.e., the usual Caputo fractional derivative and a new definition recently proposed by Caputo and Fabrizio. The model predictions have been compared to experimental results concerning the permeation of two different compounds through human skin in vivo, such as piroxicam, an anti-inflammatory drug, and 4-cyanophenol, a test chemical model compound. Moreover, we have also considered water penetration across human stratum corneum and the diffusion of an antiviral agent employed as model drugs across the skin of male hairless rats. In all cases, a satisfactory good agreement based on the diffusion with memory has been found. However, the model based on the new definition of fractional derivative gives a better description of the experimental data, on the basis of the residuals analysis. The use of the new definition widens the applicability of the fractional derivative to diffusion processes in highly heterogeneous systems.

  19. Evidence-based Review for the Influence of NSAIDs on Female Fertility%非甾体抗炎药对女性生育影响的循证评价

    Institute of Scientific and Technical Information of China (English)

    杨敏; 牟金金; 蒋学华

    2012-01-01

    OBJECTIVE: To conduct evidence-based evaluation for the influence of NSAIDs on female fertility. METHODS: We searched Pubmed, Cochrane laboratory, EMbase, SCI, CNKI, collect relevant literature, classify and evaluate the evidence by the methods of evidence-based medicine. RESULTS: A total of 8 NSAIDs were collected. The current evidence revealed that NSAIDs could inhibit ovulation in female reversibly. Ibuprofen and meloxicam were A class, indometacin and rofecoxib were B class and etoricoxib, diclofenac, piroxicam and naproxen were C class. CONCLUSION: NSAIDs could inhibit ovulation in female reversibly, and women willing for a baby should avoid NSAIDs.%目的:对非甾体抗炎药对女性生育的影响进行循证评价.方法:计算机检索Pubmed、Cochrane图书馆、EMBase、SCI、中国期刊全文数据库等,全面收集相关文献,并应用循证医学的方法,对证据进行分类评价.结果:共检索到8个非甾体抗炎药,结果均表明其对女性生育有可逆性的抑制作用,其中布洛芬、美洛昔康为A级,吲哚美辛、罗非昔布为B级,依托昔布、双氯芬酸、吡罗昔康、萘普生为C级.结论:非甾体抗炎药对女性生育有可逆性的抑制作用,有生育计划的女性应尽量避免非甾体抗炎药的应用.

  20. Phytochemical constituents,analgesic and anti-inflammatory effects of methanol extract of Triumfetta rhomboidea leaves in animal models

    Institute of Scientific and Technical Information of China (English)

    Uche FI; Okunna BU

    2009-01-01

    Objective:To investigate the analgesic and anti-inflammatory effects of the methanolic extract of the leaves of Triumfetta rhomboidea on mice and rats respectively.And to screen the phytochemical constituent of the ex-tract.Methods:The analgesic effect was determined by acetic acid-induced writhing test in mice.While the anti-inflammatory activity was determined by egg albumin-induced oedema of the rat paw.Phytochemical screening was done by standard procedures.Results:Triumfetta rhomboidea leaf extract (50 -400 mg/kg) caused a statistically significant inhibition on the egg albumin-induced eodema or inflammation in Wister albino rats with P <0.001 (ANOVA).This effect was higher than the observed effect with Piroxicam (0.5 mg/kg) which was used as a standard.The effect was also dose-dependent.Furthermore,Triumfetta rhomboidea ex-tract caused a statistically significant reduction in the number of acetic acid-induced writhing in mice,with P<0.001 (ANOVA).These effects were also does-dependent and greater than the analgesic effects by parac-etamol which was used as a reference drug.Phytochemical screening revealed the presence of flavonoids,ster-oids,triterpenoids alkaloids,tannins and saponins in Truimfetta rhomboidea leaf extract.Conclusion:Trium-fetta rhomboidea can be recommended for acute inflammatory disorders and diseases associated with pains.This also supports its traditional use as an anti-snake bite and anti-cancer or anti-tumor agent.Further study is on the way to find out the mechanism of its action and also to isolate,identify and characterize the active principle responsible for these effects in this plant.

  1. Hierarchically structured self-supported latex films for flexible and semi-transparent electronics

    Energy Technology Data Exchange (ETDEWEB)

    Määttänen, Anni, E-mail: anni.maattanen@abo.fi [Laboratory of Physical Chemistry, Faculty of Science and Engineering, Center for Functional Materials, Åbo Akademi University, Porthaninkatu 3, 20500, Turku (Finland); Ihalainen, Petri, E-mail: petri.ihalainen@abo.fi [Laboratory of Physical Chemistry, Faculty of Science and Engineering, Center for Functional Materials, Åbo Akademi University, Porthaninkatu 3, 20500, Turku (Finland); Törngren, Björn, E-mail: bjorn.torngren@abo.fi [Laboratory of Physical Chemistry, Faculty of Science and Engineering, Center for Functional Materials, Åbo Akademi University, Porthaninkatu 3, 20500, Turku (Finland); Rosqvist, Emil, E-mail: emil.rosqvist@abo.fi [Laboratory of Physical Chemistry, Faculty of Science and Engineering, Center for Functional Materials, Åbo Akademi University, Porthaninkatu 3, 20500, Turku (Finland); Pesonen, Markus, E-mail: markus.pesonen@abo.fi [Physics, Faculty of Science and Engineering, Center for Functional Materials, Åbo Akademi University, Porthaninkatu 3, 20500, Turku (Finland); Peltonen, Jouko, E-mail: jouko.peltonen@abo.fi [Laboratory of Physical Chemistry, Faculty of Science and Engineering, Center for Functional Materials, Åbo Akademi University, Porthaninkatu 3, 20500, Turku (Finland)

    2016-02-28

    Graphical abstract: - Highlights: • Transparent self-supported latex films were fabricated by a peel-off process. • Various template substrates were used for creating e.g. hierarchically structured latex films. • Ultra-thin and semi-transparent conductive gold electrodes were evaporated on the latex films.Electrochemical experiments were carried out to verify the applicability of the electrodes. - Abstract: Different length scale alterations in topography, surface texture, and symmetry are known to evoke diverse cell behavior, including adhesion, orientation, motility, cytoskeletal condensation, and modulation of intracellular signaling pathways. In this work, self-supported latex films with well-defined isotropic/anisotropic surface features and hierarchical morphologies were fabricated by a peel-off process from different template surfaces. In addition, the latex films were used as substrates for evaporated ultrathin gold films with nominal thicknesses of 10 and 20 nm. Optical properties and topography of the samples were characterized using UV–vis spectroscopy and Atomic Force Microscopy (AFM) measurements, respectively. The latex films showed high-level transmittance of visible light, enabling the fabrication of semi-transparent gold electrodes. Electrochemical impedance spectroscopy (EIS) measurements were carried out for a number of days to investigate the long-term stability of the electrodes. The effect of 1-octadecanethiol (ODT) and HS(CH{sub 2}){sub 11}OH (MuOH) thiolation and protein (human serum albumin, HSA) adsorption on the impedance and capacitance was studied. In addition, cyclic voltammetry (CV) measurements were carried out to determine active medicinal components, i.e., caffeic acid with interesting biological activities and poorly water-soluble anti-inflammatory drug, piroxicam. The results show that the fabrication procedure presented in this study enables the formation of platforms with hierarchical morphologies for multimodal

  2. Nasal Drug Absorption from Powder Formulations: Effect of Fluid Volume Changes on the Mucosal Surface.

    Science.gov (United States)

    Tanaka, Akiko; Furubayashi, Tomoyuki; Enomura, Yuki; Hori, Tomoki; Shimomura, Rina; Maeda, Chiaki; Kimura, Shunsuke; Inoue, Daisuke; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2017-01-01

    The effect of changes in the mucosal fluid volume on the nasal drug absorption of powder formulations was evaluated using warfarin (WF), piroxicam (PXC), and norfloxacin (NFX) as model drugs. Lactose and sodium chloride (NaCl), which are water soluble and small-sized chemicals that increase osmotic pressure after dissolution, were used as excipients to change the mucosal fluid volume. The in vitro study using a Madin-Darby canine kidney (MDCK) cell monolayer indicated that lactose and NaCl, sprayed over the surface of air interface monolayers, increased the fluid volume on the monolayer surface and enhanced the transepithelial transport of the model drugs. The in vivo animal study indicated that the nasal absorption of PXC is enhanced by lactose and NaCl after nasal administration of the powder formulations. This is likely due to the enhanced dissolution of PXC on fluid-rich nasal mucosa and an increase in the effective surface area for drug permeation, which lead to better nasal absorption. However, both excipients failed to increase the nasal absorption of WF and NFX. To clarify the mechanism of the drug-dependent effect of lactose and NaCl, the nasal residence of the formulation was examined using FD70 as a non-absorbable marker. The nasal clearance of FD70 was enhanced by lactose and NaCl, leading to a decrease in the nasal drug absorption. Lactose and NaCl caused no damage to the nasal tissue. These results indicate that the addition of water-soluble excipients such as lactose to powder formulations can enhance the nasal absorption of highly permeable but poorly soluble drugs.

  3. Effects of non-steroidal anti-inflammatory drugs on cyanobacteria and algae in laboratory strains and in natural algal assemblages.

    Science.gov (United States)

    Bácsi, István; B-Béres, Viktória; Kókai, Zsuzsanna; Gonda, Sándor; Novák, Zoltán; Nagy, Sándor Alex; Vasas, Gábor

    2016-05-01

    In recent years measurable concentrations of non-steroidal anti-inflammatory drugs (NSAIDs) have been shown in the aquatic environment as a result of increasing human consumption. Effects of five frequently used non-steroidal anti-inflammatory drugs (diclofenac, diflunisal, ibuprofen, mefenamic acid and piroxicam in 0.1 mg ml(-1) concentration) in batch cultures of cyanobacteria (Synechococcus elongatus, Microcystis aeruginosa, Cylindrospermopsis raciborskii), and eukaryotic algae (Desmodesmus communis, Haematococcus pluvialis, Cryptomonas ovata) were studied. Furthermore, the effects of the same concentrations of NSAIDs were investigated in natural algal assemblages in microcosms. According to the changes of chlorophyll-a content, unicellular cyanobacteria seemed to be more tolerant to NSAIDs than eukaryotic algae in laboratory experiments. Growth of eukaryotic algae was reduced by all drugs, the cryptomonad C. ovata was the most sensitive to NSAIDs, while the flagellated green alga H. pluvialis was more sensitive than the non-motile green alga D. communis. NSAID treatments had weaker impact in the natural assemblages dominated by cyanobacteria than in the ones dominated by eukaryotic algae, confirming the results of laboratory experiments. Diversity and number of functional groups did not change notably in cyanobacteria dominated assemblages, while they decreased significantly in eukaryotic algae dominated ones compared to controls. The results highlight that cyanobacteria (especially unicellular ones) are less sensitive to the studied, mostly hardly degradable NSAIDs, which suggest that their accumulation in water bodies may contribute to the expansion of cyanobacterial mass productions in appropriate environmental circumstances by pushing back eukaryotic algae. Thus, these contaminants require special attention during wastewater treatment and monitoring of surface waters.

  4. Laboratory monitoring of patients treated with antihypertensive drugs and newly exposed to non steroidal anti-inflammatory drugs: a cohort study.

    Directory of Open Access Journals (Sweden)

    Jean-Pascal Fournier

    Full Text Available BACKGROUND: Drug-Drug Interactions between Non Steroidal Anti-Inflammatory Drugs (NSAIDs and Angiotensin Converting Enzyme Inhibitors (ACEIs, Angiotensin Receptor Blocker (ARBs or diuretics can lead to renal failure and hyperkalemia. Thus, monitoring of serum creatinine and potassium is recommended when a first dispensing of NSAID occur in patients treated with these drugs. METHODS: We conducted a pharmacoepidemiological retrospective cohort study using data from the French Health Insurance Reimbursement Database to evaluate the proportion of serum creatinine and potassium laboratory monitoring in patients treated with ACEI, ARB or diuretic and receiving a first dispensing of NSAID. We described the first dispensing of NSAID among 3,500 patients of a 4-year cohort (6,633 patients treated with antihypertensive drugs and analyzed serum creatinine and potassium laboratory monitoring within the 3 weeks after the first NSAID dispensing. RESULTS: General Practitioners were the most frequent prescribers of NSAIDs (85.5%, 95% CI: 84.3-86.6. The more commonly prescribed NSAIDs were ibuprofen (20%, ketoprofen (15%, diclofenac (15% and piroxicam (12%. Serum creatinine and potassium monitoring was 10.7% (95% CI: 9.5-11.8 in patients treated by ACEIs, ARBs or diuretics. Overall, monitoring was more frequently performed to women aged over 60, treated with digoxin or glucose lowering drugs, but not to patients treated with ACEIs, ARBs or diuretics. Monitoring was more frequent when NSAIDs' prescribers were cardiologists or anesthesiologists. CONCLUSION: Monitoring of serum creatinine and potassium of patients treated with ACEIs, ARBs or diuretics and receiving a first NSAID dispensing is insufficiently performed and needs to be reinforced through specific interventions.

  5. MDMA increases glutamate release and reduces parvalbumin-positive GABAergic cells in the dorsal hippocampus of the rat: role of cyclooxygenase.

    Science.gov (United States)

    Anneken, John H; Cunningham, Jacobi I; Collins, Stuart A; Yamamoto, Bryan K; Gudelsky, Gary A

    2013-03-01

    3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a popular drug of abuse with well-documented acute effects on serotonergic, dopaminergic, and cholinergic transmitter systems, as well as evidence of long-term disruption of serotoninergic systems in the rat brain. Recently, it was demonstrated that MDMA evokes a delayed and sustained increase in glutamate release in the hippocampus. The purpose of the present study was to determine the role of inflammatory mediators in the MDMA-induced increase in glutamate release, as well as the contribution of inflammatory pathways in the persistent neurochemical toxicity associated with repeated MDMA treatment. Treatment with the non-selective cyclooxygenase (COX) inhibitor ketoprofen and the COX-2 selective inhibitor nimesulide attenuated the increase in extracellular glutamate in the hippocampus evoked by repeated MDMA exposure (10 mg/kg, i.p., every 2 h); no attenuation was observed in rats treated with the COX-1 selective inhibitor piroxicam. Reverse dialysis of a major product of COX activity, prostaglandin E2, also resulted in a significant increase in extracellular glutamate in the hippocampus . Repeated exposure to MDMA diminished the number of parvalbumin-positive GABA interneurons in the dentate gyrus of the hippocampus, an effect that was attenuated by ketoprofen treatment. However, COX inhibition with ketoprofen did not prevent the long-term depletion of 5-HT in the hippocampus evoked by MDMA treatment. These data are supportive of the view that cyclooxygenase activity contributes to the mechanism underlying both the increased release of glutamate and decreased number of GABA interneurons in the rat hippocampus produced by repeated MDMA exposure.

  6. Is the sulphonamide radical in the celecoxib molecule essential for its analgesic activity?

    Science.gov (United States)

    Gassani, Beatriz Carvalho Andraus; Rezende, Rafael Machado; Paiva-Lima, Patrícia; Ferreira-Alves, Dalton L; dos Reis, Webster Glayser Pimenta; Bakhle, Y S; de Francischi, Janetti Nogueira

    2010-11-01

    In a model of peripherally induced inflammatory pain in rats, selective inhibitors of cyclooxygenase (COX)-2 raised nociceptive thresholds above basal values, an effect referred to as "hypoalgesia". However other, non-selective, inhibitors of COX (indomethacin, piroxicam) or a selective inhibitor of COX-1 did not induce hypoalgesia in this model, implying that COX inhibition was not causally related to the hypoalgesic effect. Here, we have assessed whether other COX-2 inhibitors or other sulphonamides, apart from celecoxib could exhibit hypoalgesia in our model of inflammatory pain. Inflammation was induced in one hind paw of rats by intraplantar injection of carrageenan (250 μg). Nociceptive thresholds to mechanical stimulation were measured in the inflamed and contralateral paws for 6 h after carrageenan. Three sulphonamides, celecoxib itself, furosemide (a loop diuretic), acetazolamide (a carbonic anhydrase inhibitor), or a selective COX-2 inhibitor lacking the sulphonamide group, lumiracoxib, were injected s.c., 30 min before the pro-inflammatory stimulus. Naltrexone, a non-selective opioid antagonist was also administered s.c., 30 min before test drugs. Furosemide and acetazolamide dose-dependently induced hypoalgesia in the inflamed paw, as did celecoxib. However, lumiracoxib only produced anti-hyperalgesia. Pre-treatment with naltrexone completely prevented the hypoalgesia induced by the sulphonamides, but only partially prevented the anti-hyperalgesic effect of lumiracoxib. Taken together, our results suggest that the sulphonamide group in the structure of celecoxib is more critical for the development of hypoalgesia in our model than its ability to inhibit COX-2. Further, other sulphonamides lacking significant COX inhibition were also able to exhibit hypoalgesic effects, mediated by the endogenous opioid system.

  7. Topical Nonsteroidal Anti-Inflammatory Drugs: The Importance of Drug, Delivery, and Therapeutic Outcome.

    Science.gov (United States)

    Barkin, Robert L

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of pain associated with a variety of indications, including arthritic conditions, but their usefulness is often limited by dose-dependent adverse events (AEs), such as gastrointestinal disturbances, cardiovascular events, and renal toxicity. The risk of such effects could be reduced by the use of topical formulations, which offer the potential to deliver analgesic concentrations locally, at the site of inflammation, while minimizing systemic concentrations. The topical preparations currently approved in the United States are diclofenac sodium 1.5% topical solution (containing dimethyl sulfoxide as a penetration enhancer), diclofenac sodium gel 1%, and a diclofenac hydroxyethylpyrrolidine 1.3% patch. Each of these topical NSAIDs provide drug delivery to subcutaneous tissues for the management of pain associated with osteoarthritis or soft-tissue injuries. Furthermore, these formulations are not significantly associated with the systemic AEs associated with oral NSAIDs; the most common AEs associated with topical formulations are local skin reactions, which are usually mild and self-limiting. Other topical NSAID preparations approved in the European Union include ibuprofen creams and gels, ketoprofen gel, felbinac gel and cutaneous foam, and piroxicam gel. Meta-analyses have confirmed the efficacy and safety of these preparations. However, it is important to recognize that pharmacokinetic absorption from topical formulations can vary markedly, even between different formulations of the same drug, depending on the agent, the underlying disorder, and the site of application. It is therefore essential to consider the patient, the drug, and the drug delivery mechanism when selecting a topical NSAID preparation.

  8. Anti-inflammatory activity of orpanoxin administered orally and topically to rodents.

    Science.gov (United States)

    Brooks, R R; Bonk, K R; Decker, G E; Miller, K E

    1985-07-01

    Orpanoxin, a nonsteroidal anti-inflammatory drug (NSAID) lacking gastric ulcerogenic effects in the therapeutic dose range in rats, was compared with six reference NSAIDs for oral activity in the rat paw carrageenin-induced edema assay. Tested NSAIDs were ranked on the basis of oral mg/kg ED50 values: piroxicam, 0.55; orpanoxin, 35.6; diflunisal, 59.6; benoxaprofen, greater than 300; tolmetin sodium, greater than 300; and sulindac, greater than 300. Zomepirac sodium was inactive. Only the three most potent compounds produced greater than 60% inhibition of edema. Inhibition was generally greater at 4 h than at 6 h post carrageenin for all compounds. Oral activity of orpanoxin was also demonstrated in the guinea-pig u.v.-induced erythema model (ED50 = 24.2 mg/kg p.o. when given 1 h before irradiation) and in the mouse ear croton oil induced edema test (ED50 value = 131 mg/kg p.o.). Topical activity of orpanoxin was assessed in both the guinea-pig and mouse models. In the guinea-pig u.v.-induced erythema model, application (1 h after u.v.) of 1, 5, and 10% (w/v) orpanoxin creams (containing 10% urea) significantly inhibited erythema at 2, 3, and 4 h post-irradiation. Orpanoxin, mefenamic acid, and indomethacin as 1% creams inhibited total erythema scores 70, 92 and 74%, respectively. Evidence for topical activity in the mouse ear assay was also obtained for orpanoxin in diethyl ether or 10% urea cream, but not in dimethylsulfoxide. It was concluded that orpanoxin has anti-inflammatory activity comparable to reference NSAIDs in the rat paw edema test, is active orally in rat, mouse, and guinea-pig models, and shows topical activity in the guinea-pig and the mouse.

  9. Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

    Energy Technology Data Exchange (ETDEWEB)

    Nadanaciva, Sashi [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States); Aleo, Michael D. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Strock, Christopher J. [Cyprotex US, Watertown, MA 02472 (United States); Stedman, Donald B. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Wang, Huijun [Computational Sciences, Pfizer Inc., Groton, CT 06340 (United States); Will, Yvonne, E-mail: yvonne.will@pfizer.com [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States)

    2013-10-15

    To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary.

  10. Prostaglandin H2 synthase-1 and -2 expression in guinea pig gestational tissues during late pregnancy and parturition.

    Science.gov (United States)

    Welsh, Toni; Mitchell, Carolyn M; Walters, William A; Mesiano, Sam; Zakar, Tamas

    2005-12-15

    Increased intrauterine prostaglandin (PG) production is crucial for the initiation of parturition. To investigate the mechanisms controlling intrauterine PG synthesis, we examined the expression of the key PG biosynthetic isoenzymes, PG-H2 synthase (PTGS)-1 and -2, in the amnion, visceral yolk sac (VYS), placenta and myo-endometrium of pregnant guinea pigs. This animal model was chosen because the hormonal milieu of pregnancy and the role of PGs in the hormonal control of parturition are similar to those in the human. PTGS1 mRNA abundance, measured by real-time RT-PCR, increased in the amnion and the placenta during the last third of gestation. During labour, PTGS1 mRNA levels decreased precipitously in all four tissues. PTGS1 protein abundance, assessed by immunoblotting, increased to high levels in the amnion and the placenta by the end of pregnancy and remained high during labour. PTGS2 mRNA expression was higher in the placenta than in the other tissues, but did not change before and during labour. PTGS2 protein expression decreased in the placenta and remained low in the other tissues during labour. Immunohistochemistry showed pervasive PTGS1 protein expression in the amnion and strong expression in the parietal yolk sac membrane (PYS) covering the placenta. PTGS2 was expressed in the PYS and the endometrium. The PTGS inhibitor piroxicam, administered in doses that inhibited PTGS1 but not PTGS2, significantly prolonged gestation. These data suggest that PGs generated by intrauterine PTGS1 are involved in the timing of birth in guinea pigs. The induction of PTGS1 in the amnion and the PYS is a critical event leading to labour in guinea pigs and models analogous changes in the human gestational tissues before labour.

  11. New formulation of in situ gelling Metolose-based liquid suppository.

    Science.gov (United States)

    Pásztor, E; Makó, A; Csóka, G; Fenyvesi, Zs; Benko, R; Prosszer, M; Marton, S; Antal, I; Klebovich, I

    2011-01-01

    An in situ gelling liquid suppository is liquid at room temperature but forms a gel at body temperature. In our work, Metolose® SM-4000 (methylcellulose) is studied that basically shows thermal gelation at 68°C (2%, w/w). The objective was to study the potency of different factors (concentration, pH, additives) to change the value of thermal gelation temperature (T (t)) for Metolose® to form an in situ gelling liquid suppository. We studied the effect of Metolose® concentration, pH, and salts (sodium chloride, potassium chloride, sodium hydrogen carbonate, and sodium monohydrogen phosphate) on T (t) by viscosimetry. To choose the appropriate compound, in vitro drug release was examined. Rectal safety test was performed on rats in vivo after 12-hour application. Increasing the Metolose® concentrations (0.5-4%, w/w), T (t) can be decreased, but it also altered the consistency of gel. pH does not affect the T (t). The water-soluble salts allowed reducing the gelation temperature to 37°C. Sodium monohydrogen phosphate in 4.5% concentration was found to be the most appropriate. The impact of examined factors on in vitro drug release of piroxicam from the in situ-formed gel was characterized according to Fickian diffusion. Metolose® and the chosen salt did not cause any morphological damage on the rectal tissues. According to our study, Metolose® has the physical and chemical potential to be used as base for liquid suppositories.

  12. 环加氧酶-2抑制剂尼美舒利通过改善内皮功能和增加NO含量对抗大鼠心肌氧化应激损伤%COX-2 inhibitor nimesulide protects rat heart against oxidative stress by improving endothelial function and enhancing NO production

    Institute of Scientific and Technical Information of China (English)

    吕萍萍; 范莹; 陈文良; 沈岳良; 朱立; 王琳琳; 陈莹莹

    2007-01-01

    本文旨在研究冠状动脉内皮和NO在选择性环加氧酶2(cyclooxygenase 2,COX-2)抑制剂尼美舒利(nimesulide)对抗心肌氧化损伤中的作用.离体大鼠心脏行Langendorff灌流,给予H2O2(140 μmol/L)观察心脏收缩功能.用U-46619灌流心脏,使冠状动脉预收缩后,观察冠状动脉对内皮依赖性舒张因子5-HT和内皮非依赖性舒张因子硝普钠(sodium nitroprusside,SNP)的反应.结果显示:(1)与空白对照组(100%)相比,H2O2灌流20 min后,左心室发展压[left yentricular developed pressure,LVDP,(54.8±4.0)%],和心室内压最大变化速率[±dp/dtmax,(50.8±3.1)%和(46.2±2.9)%]明显降低.H2O2灌流前尼美舒利(5 μmol/L)预处理10min,能够显著抑制H2O2引起的LVDP和±dp/dtmax下降[(79.9±2.8)%,(80.3±2.6)%和(81.4±2.6)%,P<0.01].(2)与空白对照组相比,H2O2灌流后,5-HT和SNP引起内皮依赖性和内皮非依赖性血管舒张功能均明显下降;而尼美舒利预处理10min能明显对抗内皮依赖性血管舒张功能的下降[(-22.2±4.2)%vs H2O2组(-6.0±2.5)%,P<0.0l],但对其内皮非依赖性血管舒张功能的下降没有明显作用[(-2.0±1.8)%vs H2O2组(-7.0±3.5)%,P>0.05].(3)一氧化氮合酶(nitric oxide synthase,NOS)抑制剂L-NAME能够部分取消尼美舒利预处理对H2O2应激心脏心功能指标的改善作用[LVDP和±dp/dtmax分别为(60.2±2.1)%,(63.9±2.4)%和(63.1±2.9)%,P<0.01].同时尼美舒利预处理10 min能使H2O2应激心肌NO含量增加[(2.63±0.40)vs(1.36±0.23)nmol/gprotein,P<0.05],而L-NAME抑制此作用.(4)选择性COX-1抑制剂吡罗昔康(piroxicam)预处理不能抑制H2O2引起的LVDP和±dp/dtmax下降,但促进左心室舒张末压(left ventricular end diastolic pressure,LVEDP)升高;吡罗昔康对H2O2引起的内皮依赖性和内皮非依赖性血管舒张功能下降无显著作用.以上结果提示,选择性COX-2抑制剂尼美舒利能够对抗大鼠离体心肌氧化应激损伤,其机制可能是通过改善内

  13. Cuantificación de glibenclamida en muestras de limpieza de equipos farmacéuticos mediante cromatografía líquida de alta resolución

    Directory of Open Access Journals (Sweden)

    Alen Nils Baeza Fonte

    2012-03-01

    Full Text Available Objetivo: proponer un procedimiento analítico selectivo para la cuantificación de glibenclamida en muestras de limpieza de equipos farmacéuticos mediante cromatografía líquida de alta resolución. Métodos: la fase móvil consistió en una mezcla equivalente de volúmenes de acetonitrilo y solución amortiguadora KH2PO4 de concentración 0,037 mol/L a pH 5,25 y flujo 1,5 mL/min, en una columna Nucleosil 100 C8. La glibenclamida se inyectó con progesterona como estándar interno y empleando detector UV a una l= 230 nm. Resultados: el método resultó lineal en el intervalo de concentraciones de 0,4-150 mg/mL, teniendo como límites de detección y cuantificación 10 y 40 ng/mL respectivamente y siendo específico al analito en presencia del placebo, sus productos de degradación y a otros ingredientes farmacéuticamente activos. Se consideraron potenciales de interferencias para el método propuesto: captopril, clortalidona, dexametasona, digoxina, 8-cloroteofilina, difenhidramina HCl, fenobarbital, haloperidol, hidroclorotiazida, ácido fumárico, ketotifeno, metoclopramida HCl, piridoxina HCl, piroxicam, prednisona y nifedipino. Se identificaron: ibuprofeno, indometacina, trifluoperazina HCl, tioridazina HCl e imipramina HCl, como interferentes del procedimiento en concentraciones cercanas a 10 mg/mL. Conclusiones: el método desarrollado es sensible, rápido y especialmente selectivo para la evaluación de residuales del principio activo glibenclamida en equipos de producción de tabletas, empleando un muestreo por hisopado, y pudiera utilizarse potencialmente cuando exista sospecha de contaminación cruzada de glibenclamida con otros fármacos de los aquí descritos.

  14. FCERI and Histamine Metabolism Gene Variability in Selective Responders to NSAIDS

    Science.gov (United States)

    Amo, Gemma; Cornejo-García, José A.; García-Menaya, Jesus M.; Cordobes, Concepcion; Torres, M. J.; Esguevillas, Gara; Mayorga, Cristobalina; Martinez, Carmen; Blanca-Lopez, Natalia; Canto, Gabriela; Ramos, Alfonso; Blanca, Miguel; Agúndez, José A. G.; García-Martín, Elena

    2016-01-01

    The high-affinity IgE receptor (Fcε RI) is a heterotetramer of three subunits: Fcε RIα, Fcε RIβ, and Fcε RIγ (αβγ2) encoded by three genes designated as FCER1A, FCER1B (MS4A2), and FCER1G, respectively. Recent evidence points to FCERI gene variability as a relevant factor in the risk of developing allergic diseases. Because Fcε RI plays a key role in the events downstream of the triggering factors in immunological response, we hypothesized that FCERI gene variants might be related with the risk of, or with the clinical response to, selective (IgE mediated) non-steroidal anti-inflammatory (NSAID) hypersensitivity. From a cohort of 314 patients suffering from selective hypersensitivity to metamizole, ibuprofen, diclofenac, paracetamol, acetylsalicylic acid (ASA), propifenazone, naproxen, ketoprofen, dexketoprofen, etofenamate, aceclofenac, etoricoxib, dexibuprofen, indomethacin, oxyphenylbutazone, or piroxicam, and 585 unrelated healthy controls that tolerated these NSAIDs, we analyzed the putative effects of the FCERI SNPs FCER1A rs2494262, rs2427837, and rs2251746; FCER1B rs1441586, rs569108, and rs512555; FCER1G rs11587213, rs2070901, and rs11421. Furthermore, in order to identify additional genetic markers which might be associated with the risk of developing selective NSAID hypersensitivity, or which may modify the putative association of FCERI gene variations with risk, we analyzed polymorphisms known to affect histamine synthesis or metabolism, such as rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742, and rs1049793 in the HDC, HNMT, and DAO genes. No major genetic associations with risk or with clinical presentation, and no gene-gene interactions, or gene-phenotype interactions (including age, gender, IgE concentration, antecedents of atopy, culprit drug, or clinical presentation) were identified in patients. However, logistic regression analyses indicated that the presence of antecedents of atopy and the DAO SNP rs2052129 (GG

  15. The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2.

    Science.gov (United States)

    Hsu, A L; Ching, T T; Wang, D S; Song, X; Rangnekar, V M; Chen, C S

    2000-04-14

    This study investigates the apoptotic activity of the cyclooxygenase-2 (COX-2) inhibitor celecoxib in prostate carcinoma cells. COX-2 is constitutively expressed in androgen-responsive LNCaP and androgen-nonresponsive PC-3 cells. Exposure of these cells to celecoxib induces characteristic features of apoptosis, including morphological changes, DNA laddering, and caspase-3 activation, whereas piroxicam, a COX-1-specific inhibitor, displays no appreciable effect on either cancer cell line even after prolonged exposure. Moreover, the potency of celecoxib in apoptosis induction is significantly higher than that of other COX-2 inhibitors examined despite the observation that these inhibitors exhibit similar IC(50) in COX-2 inhibition. It is noteworthy that normal human prostate epithelial cells, expressing a marginally detectable level of COX-2, are insensitive to the induction of apoptosis by celecoxib. These data suggest a correlation between COX-2 expression and sensitivity to the apoptotic effect of the COX-2 inhibitor. In an effort to delineate the underlying mechanism, we examined the effect of celecoxib on the expression of Bcl-2 as well as the activation of the key anti-apoptotic kinase Akt. In contrast to an earlier report that attributed the apoptotic activity of NS398 in LNCaP cells to Bcl-2 down-regulation, we provide evidence that the induction of apoptosis by celecoxib in LNCaP and PC-3 cells is independent of Bcl-2. First, treatment with celecoxib does not alter the cellular Bcl-2 level in both cell lines. Second, enforced Bcl-2 expression in PC-3 cells does not confer protection against the induction of apoptosis by celecoxib. Our data show that celecoxib treatment blocks the phosphorylation of Akt. This correlation is supported by studies showing that overexpression of constitutively active Akt protects PC-3 cells from celecoxib-induced apoptosis. Nevertheless, how celecoxib down-regulates Akt is not clear because the drug does not adversely affect

  16. Evolution of supersaturation of amorphous pharmaceuticals: the effect of rate of supersaturation generation.

    Science.gov (United States)

    Sun, Dajun D; Lee, Ping I

    2013-11-04

    The combination of a rapidly dissolving and supersaturating "spring" with a precipitation retarding "parachute" has often been pursued as an effective formulation strategy for amorphous solid dispersions (ASDs) to enhance the rate and extent of oral absorption. However, the interplay between these two rate processes in achieving and maintaining supersaturation remains inadequately understood, and the effect of rate of supersaturation buildup on the overall time evolution of supersaturation during the dissolution of amorphous solids has not been explored. The objective of this study is to investigate the effect of supersaturation generation rate on the resulting kinetic solubility profiles of amorphous pharmaceuticals and to delineate the evolution of supersaturation from a mechanistic viewpoint. Experimental concentration-time curves under varying rates of supersaturation generation and recrystallization for model drugs, indomethacin (IND), naproxen (NAP) and piroxicam (PIR), were generated from infusing dissolved drug (e.g., in ethanol) into the dissolution medium and compared with that predicted from a comprehensive mechanistic model based on the classical nucleation theory taking into account both the particle growth and ripening processes. In the absence of any dissolved polymer to inhibit drug precipitation, both our experimental and predicted results show that the maximum achievable supersaturation (i.e., kinetic solubility) of the amorphous solids increases, the time to reach maximum decreases, and the rate of concentration decline in the de-supersaturation phase increases, with increasing rate of supersaturation generation (i.e., dissolution rate). Our mechanistic model also predicts the existence of an optimal supersaturation rate which maximizes the area under the curve (AUC) of the kinetic solubility concentration-time profile, which agrees well with experimental data. In the presence of a dissolved polymer from ASD dissolution, these observed trends

  17. Treatment of experimental colitis in mice with LMP-420, an inhibitor of TNF transcription

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    Cianciolo George

    2008-03-01

    Full Text Available Abstract Background LMP-420 is a boronic acid-containing purine nucleoside analogue that transcriptionally inhibits TNF production but is non-cytotoxic to TNF-producing cells. Methods This study investigated the efficacy of LMP-420 as an anti-inflammatory agent in acute and chronic colitis induced by oral administration of dextran sulfate sodium (DSS to mice and in chronic colitis following piroxicam administration to IL-10-deficient mice. The severity of colon inflammation was assessed histologically. TNF levels were measured by enzyme immunoassay. Results Administration of DSS for 7 days resulted in severe acute colitis that was associated with a marked increase in stool and colon tissue TNF levels. Initiation of therapy with intraperitoneal (i.p. LMP-420 on day 4 of DSS exposure decreased colonic TNF to near normal levels on day 7. However, neither i.p. nor oral treatment with LMP-420 affected the development or severity of acute DSS colitis. Initiation of LMP-420 therapy after 3 cycles of DSS administration to establish chronic colitis also had no effect on the severity of chronic colitis. Analysis of colonic TNF combined with longitudinal analysis of TNF and TNF receptor (TNF-RII levels in stool during the development of chronic DSS colitis demonstrated that the initially elevated colonic TNF levels returned to normal despite intense on-going inflammation in mice with chronic colitis. RAG-2-/- mice deficient in T and B cells also developed severe ongoing colitis in response to 3 cycles of DSS, but showed marked differences vs. wild type mice in stool TNF and TNF-RII in response to DSS exposure. Systemic and oral LMP-420 treatment for 16 days decreased colonic TNF levels in IL-10-deficient mice with chronic colitis, with a trend to decreased histologic inflammation for oral LMP-420. Conclusion These studies demonstrate that short-term treatment with a transcriptional inhibitor of TNF production can decrease systemic and local colonic levels

  18. The Related Substances of Ampiroxicam%安吡昔康的有关物质研究

    Institute of Scientific and Technical Information of China (English)

    张培龙; 于芳; 王颖; 杜继航

    2012-01-01

    The impurities in the ampiroxicam (1) synthesis process were separated and purified. The structure of one compound was confirmed by LC-MS and 1H NMR to be 6-methyl-6H-7-oxopyrido[l,2-a]pyrimido[5,4-c]-l,2-benzothiazine-5,5-dioxide (3). An HPLC method was established for the determination of the related substances in 1. An ODS column was used with the mobile phase of 0.05 mol/L potassium dihydrogen phosphate buffer solution (adjusted to pH 4.5 with phosphoric acid)-acetonitrile by gradient elution at the detection wavelength of 314 nm. The calibration curves of the related substances including piroxicam (2) and 3 were linear in the concentration range of 0.3 - 1μg/ml. Their average recoveries were 105.0% and 100.8 %, with RSDs of 1.19% and 0.91 %.%对安吡昔康(1)工艺中产生的杂质进行分离、提纯,采用LC-MS及1H NMR进行结构确证为6-甲基-6H-7-氧代吡啶并[1,2-a]嘧啶并[5,4-c]-1,2-苯并噻嗪-5,5-二氧化物(3).建立了高效液相色谱法测定1的有关物质.采用ODS色谱柱,以0.05 mol/L磷酸二氢钾溶液(用磷酸调至pH 4.5)-乙腈为流动相,梯度洗脱,检测波长314 nm.1的有关物质吡罗昔康(2)和3在0.3~1μg/ml浓度范围内线性关系良好,平均回收率为105.0%和100.8%,RSD为1.19%和0.91%.

  19. Comparison effect of acupoint injection by mixture of methyl prednisolone acetate and lidocain with oral medication in acute low back pain

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    Mohammad Javad Hadianfard

    2009-01-01

    Full Text Available (Received 30 December, 2009 ; Accepted 10 August, 2009AbstractBackground and purpose: Acupuncture is a treatment useful in reducing and eliminating pain. This study was undertaken to present a simple and fast method of treatment in acute radicular low back pain by injection of acupoints.Materials and methods: Fifty patients with acute low back pain with positive Straight Leg Raising (SLR test were enrolled in the study. The patients were randomly divided into two equal groups. Physical examination in the pilot study showed that patients have five tender acupoints including BL-57, BL-40, BL-36 or 37, BL-23 and GB-30. The subjects in the first group were injected in at least 3 acupoints of these 5 points. Injection was done only once by mixing 2cc of lidocaine 2% and 1ml of methylprednisolone acetate (40 mg. The subjects of the second group took medication such as piroxicam 20 mg orally, methocarbamol 1500 mg and diazepam 10 mg daily for one week. Dependent variables were measured including; pain intensity was measured by Numerical Pain Rating Scale (NPRS, balance and weight bearing ability was measured by Standard Hopping Scale (SHS, sciatic nerve stretch was measured by SLR, patients’ function was measured by Back Pain Functional Scale (BPFS questioner.Results: Both groups were equal statistically before starting treatment, but there was a significant difference between them in variables BPFS and SHS 10 days after treatment. The mean of decreased pain intensity in NPRS and SLR were equal but effective in both group on the 10th day. Conclusion: It seems that effect of injection with acupuncture points in acute low back pain not only is as good as medical treatment but it is also better than that. In this treatment, there was no report of secondary complication to treatment. So, in patients with acute radicular LBP, injection of tender acupoints is an effective, safe, economical, and time saving method of treatment. J Mazand Univ Med Sci 2009

  20. Correlation between drug–drug interaction-induced Stevens–Johnson syndrome and related deaths in Taiwan

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    Fu-Jen Cheng

    2016-04-01

    Full Text Available Concomitant use of some drugs can lead to interactions between them resulting in severe adverse effects. To date, there are few reports of incidences of Stevens-Johnson syndrome (SJS associated with combination drug administration. Therefore, we studied the relationship between drug combinations and SJS-related mortality, with the hope that a retrospective study of this nature would provide information crucial for the prevention of future drug-drug interaction related deaths attributable to SJS. This retrospective longitudinal study used mortality cases from 1999 to 2008 that were diagnosed as erythema multiforme (International Classification of Diseases, Ninth Revision, Clinical Modification 695.1 from the National Health Insurance database in Taiwan. Statistical comparisons of the results were performed using analysis of variance (ANOVA, independent sample t-tests, and odds ratio (OR. In this way, the relationship between combinations of SJS-inducing drugs and mortality could be determined. A total of 111 patients who had died, including 63 males and 48 females (66.0 ± 20 and 70.0 ± 17.7 years, respectively, were suspected of having experienced drug-drug interaction-related adverse effects. The associated drug combinations included allopurinol and ampicillin (p = 0.049, carbamazepine and sulfamethoxazole/trimethoprim (TMP (p < 0.0001, carbamazepine and phenytoin (p < 0.0001, sulfamethoxazole/TMP and phenytoin (p = 0.015, sulfadoxine and piroxicam (p = 0.045, phenobarbital and cephalexin (p < 0.0001, ampicillin and erythromycin (p < 0.0001, erythromycin and minocycline (p < 0.0001, and vancomycin and ethambutol (p < 0.0001 administered 1 month before the patients' deaths. Caution should be exercised when administering any drugs that may possibly induce SJS. In addition, attention should be paid to ensure prompt identification of possible drug-drug interactions, and patients should be closely monitored. Furthermore