33 research outputs found

    Učinci adheziva osjetljivih na tlak i kemijskih promotora na permeaciju fentanila kroz kožu štakora

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    Drug-in-adhesive patches (DIAPs) of fentanyl were formulated using various pressure sensitive adhesives (PSAs) and various chemical permeation enhancers (CPEs). The effects of the PSAs and CPEs on skin permeation of fentanyl from DIAPs were evaluated using modified jacketed Franz diffusion cells fitted with excised rat abdominal skin. It was demonstrated that permeation rate or steady state flux (Jss) of the drug through the excised rat skin was dependent on the viscosity and type of acrylic PSA as well as the type of CPE. Among different acrylic PSAs, Duro-Tak® 2054 and Duro-Tak® 2516 showed the highest Jss of 1.95 μg cm-2 h-1 and the lowest Jss of 1.43 μg cm-2 h-1, respectively. Among the various CPEs used, propylene glycol and polyethylene glycol 400 showed 1.61 and 1.18, the highest and lowest enhancement ratio (ER) on the skin permeation of fentanyl, respectively. Oleic acid and cetyl alcohol moderately increased the skin permeation of fentanyl. It was also shown that increasing the concentration of CPE led to reduction in adhesion property of PSA as measured by 180° peeling strength test. Moreover, it was found that the permeation rate increased as the fentanyl loading increased from 1 to 3%. The skin permeation rate of fentanyl did not increase significantly beyond 3% drug loading. It was concluded that PG as a CPE and cosolvent in 10% m/m with 3% fentanyl loading in Duro-Tak 2054 showed an effective monolithic DIAP for the development of a transdermal therapeutic system for fentanyl.Pripravljeni su transdermalni adhezivni flasteri fentanila (DIAPs) koristeći različite adhezive osjetljivih na tlak (PSAs) i kemijske promotore permeabilnosti (CPEs). Njihovi učinci na permeabilnost fentanila evaluirani su pomoću modificirane Franzove difuzijske ćelije s membranom od kože s abdomena štakora. Brzina permeabilnosti (Jss) ovisi o viskoznosti i vrsti akrilnih adheziva i o vrsti promotora. Najveća vrijednost Jss = 1,95 μg cm-2 h-1 postignuta je s Duro-Tak® 2054, a najmanja (Jss = 1,43 μg cm-2 h-1) s Duro-Tak® 2516. Među različitim promotorima propilen glikol i polietilen glikol 400 pokazali su najveći (1,61) i najmanji (1,18) omjer poboljšanja (ER) permeabilnosti. Oleinska kiselina i cetil alkohol umjereno su povećali permeabilnost fentanila. Za mjerenje adhezivnih svojstava upotrebljena je "metoda ljuštenja". Povećanje koncentracije CPE smanjilo je adhezivna svojstva PSA. Kada je udio fentanila u flasteru povišen s 1 na 3%, brzina permeabilnosti se povećala, dok daljnje povećanje udjela fentanila nije značajno utjecalo na brzinu. Pripravak s 10% propilen glikola i 3% fentanila u Duro-Tak 2054 pokazao se kao učinkoviti transdermalni terapijski sustav za fentanil

    Dizajniranje i in vitro evaluacija transdermalnih flastera fentanila

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    The present research was designed to evaluate different matrix, drug-in-adhesive and reservoir formulations of fentanyl transdermal patches. The target was to design drug-in-adhesive patches (DIAPs); a full factorial design was used. Different types and amounts of liquid, pressure-sensitive adhesives (PSAs) were used and evaluated with respect to drug release and adhesive properties. A very simple but precise method, the simplified peel 180° test, was developed to measure and compare adhesive properties of transdermal patches. The results showed that release kinetics obeyed the square root of time or Higuchi model, indicating the diffusion controlled release mechanism. It was found that the amount of fentanyl needed for each 10 cm2 three-days DIAP should be 3.3 mg. The respective amounts for reservoir and matrix patches were 2.5 and 5 mg. It was concluded that acrylic PSAs showed the best adhesion and release properties.U radu su evaluirani različiti matriksni, adhezivni i spremišni ljekoviti oblici za transdermalnu primjenu fentanila. U dizajniranju adhezivnih flastera (DIAPs) uspotrebljene su različite vrste i količine tekućih adheziva osjetljivih na tlak (PSAs). Evaluirano je oslobađanje ljekovite tvari i adhezivna svojstva. Za mjerenje i usporedbu adhezivnih svojstava transdermalnih flastera razvijena je vrlo jednostavna, ali precizna "metoda ljuštenja". Rezultati su pokazali da kinetika oslobađanja slijedi kvadratni korijen vremena (Higuchijev model), ukazujući da se ljekovita tvar oslobađa difuzijom. Pokazalo se da je za svakih 10 cm2 DIAP-a za trodnevnu uporabu potrebno 3,3 mg fentanila. Ta količina je za spremišne i matriksne flastere iznosila 2,5, odnosno 5 mg. Najbolja adhezivna svojstva i oslobađanje fentanila bilo je iz akrilatnih pripravaka

    Imatinib Metabolism and Disposition in Isolated Rat Perfused Liver: Imatinib Metabolism and Disposition in Isolated Rat Perfused Liver

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    Imatinib is an orally administered tyrosine kinase inhibitor which inhibits the Bcr-Abl protein-tyrosine kinase with high selectivity. Imatinib is rapidly absorbed from the gut, after oral intake and has an almost absolute bioavailability of 98%. The metabolism of imatinib is mediated by the cytochrome P450 (CYP) isoenzymes in the liver and gut wall. CGP74588 is a major active metabolite of imatinib. The study was performed on Male Sprague-Dawley rats (250-300 g) housing under artificial light on a 12-h light/dark cycle with free access to standard laboratory chow and water. Re-circulating (at imatinib concentration of 1 and 5 μg/ml) and single-pass (imatinib dose of 1mg) perfusion modes in the presence and absence of BSA were tested. Throughout the experiment, perfusate temperature (37± 0.5 C°), pH (7.4±0.2) and liver viability (ALT and AST) were monitored. The concentrations of imatinib and its main metabolite in perfusion buffer and liver homogenate were determined by a validated HPLC method.No metabolite was detected in outlet perfusate in all conditions. However, negligible amounts of metabolite were found in liver homogenate at 1 and 5 μg/ml imatinib concentrations in re-circulating perfusion mode. The rapid and remarkable disappearance of imatinib from perfusate was related to its accumulation in liver. Statistical moment definition was used to calculate some pharmacokinetic parameters. These calculations also confirmed liver accumulation and slow and sustained dissociation of imatinib from liver

    The Evaluation of the possible effect of positive end expiratory pressure (PEEP) on pharmacokinetics of phenytoin in patients with acute brain injury under mechanical ventilation

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    Preliminary data suggests that vital physiologic support measures and free fraction of phenytoin are altered following head trauma. Therefore, we conducted a prospective, randomized controlled study to determine the correlation of albumin concentration and unbound phenytoin plasma concentration following head injury. Ten adult head trauma patients in the neurosurgical intensive care unit receiving phenytoin for the seizure prophylactic treatment were studied for their free and total plasma phenytoin concentration in peak and trough times and their respective albumin concentration. Free and total phenytoin levels were determined by both liquid chromatography and florescence polarization immunoassay (Eclair) of plasma samples after ultrafiltration and deproteinization. No significant difference was found in the plasma concentration measured with HPLC or FPIA while a marked correlation was noted between plasma albumin and free phenytoin concentration (r2=0.85). The total and free phenytoin concentrations were not significantly correlated (r2=0.60). A remarkable difference (P<0.05) was noticed when doses in patients were adjusted on the basis of total plasma phenytoin and calculated plasma phenytoin adjusted for serum albumin. Therefore, therapeutic monitoring in neurosurgical patients receiving phenytoin should be performed on the basis of pharmacologically active component (free fraction), rather than total phenytoin which is presently performed in the clinics.8 page(s

    Synergistic Effect of Honey and Propolis on Cutaneous Wound Healing in Rats

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    Accelerating wound healing is now considered as a principle clinical treatment and increasing the quality and speed of healing which has always been emphasized by the scientists. Propolis and honey are natural bee products with wide range of biological and medicinal properties. This study was aimed to determine the synergistic effect of honey and propolis in wound healing of rat skin. A total of 75 Wistar rats weighing 200-250 gr were placed under general anesthesia and sterile conditions. Then a square shape wound with 1.5*1.5 mm dimension was made on the back of the neck. Animals were randomly divided into control, honey, propolis, combined honey propolis and phenytoin 1% groups, respectively. Rats were randomly divided into the following groups: 4th, 7th and, 14th days of treatment in each period of study. Wound area in the experimental group was covered once daily with a fixed amount of thyme honey, propolis, propolis and honey and phenytoin cream (1%), the control group did not receive any treatment. For histological studies, during the fourth, seventh and fourteenth day’s rats were sacrificed and samples were taken from the wound and adjacent skin. After histological staining fibroblast, neutrophils, macrophages and vascular sections were counted in the wound bed. The macroscopic and microscopic evaluations showed that the percentage of wound healing on different days in the experimental and control groups were significant (P<0.05). The macroscopic and microscopic evaluation showed that the percentage of wound healing on different days in combined propolis and honey experimental group was significantly different from the control group (Multivariate ANOVA test) (P<0.05). Combined application of propolis and honey on the open wound healing in rats has a synergistic effect
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