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RELEASE AND PERMEATION OF INDOMETHACIN FROM PHOSPHOLIPID COMPLEX FILM GENERATED FROM SPRAY FORMULATIONS

100%
Buatong W., Nakpheng T., Dechraksa J., Saisamuth S.-a., Kongkhao W., Srichana T.
Acta Poloniae Pharmaceutica - Drug Research
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2019
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vol. 76
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issue 2
329-339
EN
An indomethacin topical spray was prepared using lecithin and a cholesterol derivative as a phospholipid complex in a film. Polyvinylpyrrolidone (PVP) was used as a film-forming agent. Drug penetration through keratinocytes was evaluated as well as cytotoxicity to the keratinocytes and fibroblast cells. The results reveal that the PVP concentration provided fine droplets under a microscope with a low contact angle (12.07°-22.53°). Incorporating PVP in the formulation reduced the hydrodynamic radius or size by 20 times. The SEM and TEM results showed smoother surfaces of the thin film for larger quantities of the PVP film-forming agent in the formulations. It also gave the highest drug penetration when the PVP was 0.5%. However, the film-forming agent can also act as a control release barrier. The percent viabilities of the human keratinocytes and fibroblasts were higher in the indomethacin spray phospholipid complex thin film formulation than the pure drug.
2
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FORMULATION AND EVALUATION OF INDOMETHACIN LOADED NANOSPONGES FOR ORAL DELIVERY

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Abbas N., Sarwar K., Irfan M., Hussain A., Mehmood R., Arshad M. S., Shah P. A.
Acta Poloniae Pharmaceutica - Drug Research
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2018
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vol. 75
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issue 5
1201-1213
EN
Nanosponges (NS) loaded sustained release tablet formulations of a non-steroidal anti-inflammatory drug; Indomethacin were successfully developed and evaluated for their pharmaceutical properties. Twelve nanosponge formulations were fabricated by solvent diffusion method by using different ratios of drug and polymers (ethyl cellulose and polyvinyl alcohol). Particle size of all the formulations was in the nano range of 221 to 625 nm and it was found dependent on the polymer concentration. Drug loading and entrapment efficiency was ranged in 32.2 to 59.4 % and 30.1 to 64.8 %, respectively. Formulations with equal proportion of drug and polymer resulted in higher values of drug loading and entrapment efficiency. Percent yield was also found dependent on the relative drug polymer ratio with highest value of 51 % was achieved for the formulation having same drug to polymer ratio. SEM results confirmed the formation of spherical and porous structures. Structural analysis by Fourier transform infrared spectroscopy (FTIR), powder x-ray diffraction (PXRD) showed the absence of any interaction between drug and polymer. In comparison to pure drug, NS formulations showed a linear intrinsic dissolution rate (IDR) profile depicting a controlled release profile. Diffusion studies of NS formulations performed by Franz diffusion cell and dialysis bag methods showed comparable results in terms of precision and linearity of diffusion profile. Tablets prepared from the drug loaded NS showed acceptable values for hardness, friability and drug content. Release of drug from NS tablets was confirmed as sustained release behaviour.
3
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Anti-inflammatory activity of Turkey source pumpkin seed oil in rat oedema model

86%
Arslanbaş E., KARA H., KARAYİĞİT M. Ö., DOĞAN H. O., YILDIZ Ş. N.
Acta Poloniae Pharmaceutica - Drug Research
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2020
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vol. 77
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issue 2
305-312
EN
This study aimed to determine the effects of Turkey-sourced pumpkin seed oil (PSO), administered orally to rats in different dosages, to research its anti-inflammatory effect in rat oedema model, induced by carrageenan, based on different dosages, and to evaluate its effects comparatively with indomethacin. The study was conducted on 42 rats in total, divided into 7 groups (control, carr, PSO40, PSO100, PSO40+carr, PSO100+carr and indo+carr). In the study, doses of 40 and 100 mg/kg of PSO were found to significantly suppress rat paw oedema in time, and it was observed that this effect was more pronounced in the fourth hour. It was found that MDA and cytokine (TNF-α, IL-6, IL-1β) levels were inhibited, and GPX and SOD activities were enhanced in groups that received PSO and indo+carr groups. Histopathological examinations also support these findings. As a result of the study, the significant anti-inflammatory effect of Turkey-sourced PSO was attributed to the existence of unsaturated fatty acids and enriched phytochemical compounds.
4
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Antinociceptive eff ects of morphine, nefopam, indomethacin and imipramine in rats with lesion of the central serotoninergic system

58%
Kőrössy E., Świerszcz M., Nowak E., Beśka M., Bałasz M., Nowak P., Szkilnik R.
Annales Academiae Medicae Silesiensis
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2009
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vol. 63
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issue 5
7-24
EN
The aim of the present study was to examine the eff ect of the central serotoninergic lesion on the antinociceptive eff ects of morphine (5.0 mg/kg sc), nefopam (20 mg/kg ip), indomethacin (5.0 mg/kg ip) and imipramine (10 mg/kg ip) in the model of exteroceptive sensation - formalin test (chemical stimulus), and interoceptive sensation - writhing test (model of visceral pain). Furthermore monoamine synthesis rate after examined analgetics in the frontal cortex, thalamus, brain stem and spinal cord was assayed. MATERIAL AND METHODS On the 3 rd day of postnatal life male rats were administered with 5.7- DHT (70 μg/10 μl in 0.1% ascorbic acid solution ICV; 35 μg/5 μl per side); control animals received vehicle (70 μg/10 μl of 0.1% ascorbic acid solution ICV). Rats continued to be housed until 8-10 weeks, for further experimentation. RESULTS It was shown that the central serotoninergic lesion slightly modifi ed analgesia evoked by nefopam and indomethacin in formalin test but much more profound reduction in analgesia produced by morphine and indomethacin injection was observed in visceral model of nociception. In biochemical study it was shown that analgetics employed in this study (with exception of indomethacin) altered synthesis rate of serotonin (5-HT) and dopamine (DA) in the examined parts of the rats brain. The above indicates that besides serotoninergic pathway other monoaminergic systems (noradrenergic and dopaminergic) participate in the central mechanism of action of these drugs. CONCLUSION It is likely that similar nociception abnormalities may occur in patients with serotoninergic system dysfunction, so that it points out on the requirement of analgetics dosage adjustment.
PL
WSTĘP Celem pracy była ocena wpływu lezji (zniszczenia) ośrodkowego układu serotoninergicznego na przeciwbólowe działanie morfi ny (5.0 mg/kg sc), nefopamu (20 mg/kg ip), indometacyny (5.0 mg/kg ip) i imipraminy (10 mg/kg ip) w testach czucia bólu eksteroceptywnego, tj formalinowym (bodziec chemiczny) a ponadto czucia interoceptywnego, tj. bólu trzewnego w teście wicia. Ponadto zbadano wpływ stosowanych analgetyków na procesy syntezy monoamin w wybranych częściach mózgu (kora przedczołowa, wzgórze, most, rdzeń kręgowy) u szczurów kontrolnych oraz z lezją. MATERIAŁ I METODY Zniszczenie ośrodkowego układu serotoninergicznego wykonano u 3 dniowych noworodków szczurzych stosując dokomorowo 5.7-DHT w dawce 70 μg/10 μl w 0.1% roztworze kwasu askorbinowego. Właściwe testy behawioralne i biochemiczne wykonano po osiągnięciu przez zwierzęta 8 tygodnia życia. WYNIKI Wykazano, że chemiczna lezja ośrodkowego układu serotoninergicznego tylko w niewielkim stopniu modyfi kuje przeciwbólowe działanie nefopamu i indometacyny w modelu bólu zapalnego natomiast wyraźnie osłabia przeciwbólowe działanie morfi ny i indometacyny w modelu bólu trzewnego u szczurów. W badaniach biochemicznych wykazano, że stosowane leki (za wyjątkiem indometacyny) zmieniają szybkość syntezy serotoniny (5-HT) oraz dopaminy (DA) w badanych strukturach mózgu. Powyższe wskazuje, że w ośrodkowych mechanizmach analgetycznego działania stosowanych leków poza układem serotoninergicznym uczestniczą w różnym stopniu inne układy monoaminergiczne, tj. noradrenergiczny i dopaminergiczny. WNIOSKI Uzyskane wyniki przemawiają za tym, że trwała dysfunkcja ośrodkowego układu serotoninergicznego może prowadzić do zmienionej reakcji biologicznej na leki przeciwbólowe.
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