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Journal of Thermal Analysis and Calorimetry
Authors: N. Hamdi, Y. Feutelais, N. Yagoubi, D. de Girolamo, and B. Legendre

Abstract  

Indomethacin is known to exhibit polymorphism and solvates, the different forms obtained do not exhibit the same solubility and their bioavailabilities are different. It is of a prime importance to identify the various polymorphic and solvated forms. This study was carried out by: DSC (different scanning calorimetry), TG (thermogravimetric analysis), X-ray diffraction and thermomicroscopy. Seven solvates, with acetone, benzene, dichloromethane, tetrahydrofurane, propanol, chloroform and diethylether, were isolated and studied. Their formulae have been determined by thermogravimetric analysis and their X-ray patterns on powder are presented, by DSC their behaviour after desolvation is recorded, the temperature and the enthalpy of fusion are measured and by this way the form obtained is deduced.

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Physiology International
Authors: Leyla Semiha Şen, Zarife Nigar Özdemir Kumral, Gülsün Memi, Feriha Ercan, Berrak C. Yeğen, and Cumhur Yeğen

laboratory chow and had free access to water. All experimental protocols were approved by the MU Animal Care and Use Committee (approval number: 15.2010.mar.) Experimental design and surgery After overnight fasting, indomethacin (25 mg/kg in 5% NaHCO 3

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Abstract  

Indomethacin is known to exhibit polymorphism. As a consequence the various forms have different solubilities and may have different bioavailabilities. This study has been carried out with the following techniques: calorimetry, differential scanning calorimetry (DSC), thermogravimetric analysis (TG), X-ray diffraction and thermomicroscopy. Two solid forms have been prepared and studied: their melting temperature and their enthalpy of fusion are determined. The heat capacity and heat content were measured vs. the temperature for these two solid forms and for the liquid phase. This is fundamental for the determination of the stable form. More of this, with a view to study phase diagrams of indomethacin with another compound (solvent or not), the knowledge of the C p of the various forms is necessary for calculation of the liquidus curve, this allows to minimize the number of experiments.

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Orvosi Hetilap
Authors: Zoltán Döbrönte, Erzsébet Toldy, Levente Márk, Krisztina Sarang, and Lilla Lakner

515 Wagh, M. S., Sherman, S.: Indomethacin for post-ERCP pancreatitis prophylaxis. Another attempt at holy grail. Am. J. Gastroenterol., 2007, 102 , 984

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Abstract  

The polymorphic transformation of indomethacin (IMC) in the presence of Precirol during heating was investigated by differential scanning calorimetry (DSC), infrared (IR) spectroscopy, microscopic Fourier transform infrared (FT-IR)/DSC system, and powder X-ray diffractometry with heating. The results indicate that in the presence of Precirol the original γ form of IMC was first transformed to a transition state, and then to a new polymorph by heating or exposure to IR radiation. The transition state of the melted sample gave three endothermic peaks, at 34, 48 and 127°C, and one exothermic peak, at 54°C. The stable melted sample exhibited two endothermic peaks, at 58 and 127°C, which were due to the fusion of Precirol and the new polymorph of IMC, respectively. This new polymorph of IMC also exhibited two specific IR absorption peaks, at 1693 and 1675 cm−1. Microscopic FT-IR/DSC was used to examine the correlation between the structural transformation and its thermal response, and demonstrated the existence of the transition state of the melted sample. X-ray diffractometry with heating confirmed the appearance of the new polymorph of IMC in the presence of Precirol after heating.

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The effects exerted by human recombinant interleukin-1β (hrIL-1β) and the prostaglandin inhibitor indomethacin on the course of Cryptosporidium baileyi infection in chickens were studied. Daily oocyst shedding was monitored by a quantitative method throughout the experiment. Humoral immune response to C. baileyi was assessed by ELISA at 3 weeks of age while the level of cellular immune response to phytohaemagglutinin-P (PHA-P) by a skin test at 23 days of age. Parenteral application of hrIL-1b decreased oocyst shedding to 62%, but the infection ran a similar course in treated and control birds. The PHA-P skin test demonstrated increased cellular immune reaction in chickens receiving IL-1b, but there was no significant difference in the humoral responses of the two groups as detected by ELISA. On the other hand, indomethacin mixed to the feed lessened oocyst shedding to 13.7% and also shortened its duration. Immunological parameters as reflected by PHA-P skin test and ELISA results indicated enhanced cellular but unaltered humoral immune response. These data suggest that the sys- temic application of interleukin-1 can induce partial protection against C. baileyi in chickens and that prolonged, abundant oocyst shedding is due to an indometha- cin-sensitive immunodepression via the prostaglandin pathway.

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Acta Physiologica Hungarica
Authors: S. Eleawa, I. Bin-Jaliah, M. Alkhateeb, N.M.K. Bayoumy, R. Alessa, and Hussein Sakr

Filaretova L, Podvigina T, Bagaeva T, Makara G: Gastroprotective action of glucocorticoids during the formation and the healing of indomethacin-induced gastric erosions in rats. J. Physiol. Paris. 95, 201–208 (2001) Makara G

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Abstract  

This work exemplifies a general method of studying the drug excipient interactions, with the aim of predicting rapidly and inexpensively the long term stability of their mixtures. We study the physico-chemical properties of a drug (indomethacin) in the solid state and in different combinations with several excipients (PVP=polyvinylpyrrolidone, MGST=magnesium stearate, Avicel©). We compare the properties of pure compounds (untreated, or moisture/temperature conditioned) with those of binary mixtures drug:excipient which underwent the same treatment. The purpose is to find indications of interactions within the mixtures, which means a potential incompatibility of the excipient. Both morphological and thermal properties are sensitive to interactions which leave mostly unmodified the IR spectra and the X-rays patterns. In particular, we find that indomethacin does interact with PVP and MGST, but is certainly compatible with Avicel©.

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Polymorphism and solvation of indomethacin

Characterization of an indomethacin–tetrahydrofuran solvate leading to phase I

Journal of Thermal Analysis and Calorimetry
Authors: Béatrice Nicolaï, René Céolin, and Ivo Rietveld

Abstract  

Indomethacin crystallizes from solutions in tetrahydrofuran as a solvate exhibiting the mole ratio 1 indomethacin:2 tetrahydrofuran. Upon heating, desolvation into indomethacin phase I occurs through partial amorphization and transitory formation of a phase, which is different from the crystallographically known polymorphs. The X-ray powder diffraction pattern of the solvate was tentatively indexed on a triclinic lattice (a = 31.454(5) Å, b = 17.883(3) Å, c = 10.551(2) Å, α = 70.55(2)°, β = 105.31(2)°, γ = 136.70(1)°). Assuming Z = 6 (1 indomethacin + 2 tetrahydrofuran) formula units per unit cell, the solvate’s specific volume is similar to the value calculated using additivity.

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Réti , A , Barna , G , Pap , E et al. 2009 Enhancement of 5-fluorouracil efficacy on high COX-2 expressing HCA-7 cells by low dose indomethacin and NS-398 but not on low COX-2 expressing HT-29 cells Pathol Oncol Res 15 335 – 344

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