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

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

Clinical effects of topical antifungal therapy in chronic rhinosinusitis: a randomized, double-blind, placebo-controlled trial of intranasal fluconazole

Several studies have been in favor of fungi as a possible pathogenesis of chronic rhinosinusitis (CRS); however, to date, there is no scientific consensus about the use of antifungal agents in disease management. The aim of the present study was to investigate the efficacy of intranasal fluconazole in improving disease symptoms and objective outcomes of patients with CRS. A randomized, double-blind, placebo-controlled study was conducted on 54 patients who were diagnosed with CRS and had not been responsive to routine medical treatments. They were randomly assigned to receive either fluconazole nasal drop 0.2 % or placebo in addition to the standard regimen for a duration of 8 weeks. Patients’ outcomes were evaluated according to Sino-Nasal Outcome Test 20 (SNOT-20), endoscopic scores, and Computed Tomography (CT) scores. No statistically significant difference was found in SNOT-20 (p = 0.201), endoscopic (p = 0.283), and CT scores (p = 0.212) of the patients at baseline and after 8-week course of treatment between drug and placebo group. Similar to many studies, the use of topical antifungal treatment for patients with CRS was not shown to be significantly effective. However, further studies are needed to obtain high levels of consistent evidence in order to arrive at a decision whether antifungal therapy is effective in management of CRS or not

Modelling of the AC Breakdown Voltage of Point- Plane Air Gaps with Insulating Barrier

High voltage device dimensioning requires the prediction of the withstand voltage for test conditions  like impulses, surges and AC voltage. There is a large need of designer to have reliable design criteria and well-defined simulation procedure for device development. This parametric study is based on the methodology of experimental  designs.  This method allowed us  to  propose  a mathematical polynomial model. The objective of this paper is to study the discharge phenomena for a point –plane air  interval with insulating barrier between them. Firstly on experimental study of a laboratory setup that we designed to carry out the influence of parameters (geometrical) involved in the process of breakdown. The distance between electrodes and different parameters of the barrier such as its position between electrodes dimension and its holes is studied . The barrier acts as a geometrical obstacle against the direct propagation of discharge. Secondly, using results obtained by the experimental setup , we have experiments design  methodology of technique to predict the breakdown threshold voltage

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Prediction the AC Breakdown Voltage in Point/Plane Air Gaps with Barrier Using Design of Experiments

Breakdown voltage characteristics of air gaps considered a random process we have investigated how to find relevant statistical different leading to breakdown or with standing during an impulse voltage test under the same condition for a plane high voltage electrode and a grounded electrode configuration.In the present paper methods of the modelling and prediction of the AC breakdown voltage  in point-plane air gaps are investigated. An analysis based on experiments design method has been developed with indicates that.Measurements to contain some relevant information test at early stages in reduced time frame investigation were done on a point-plane with barrier varying in position and size. The barrier used was mounted vertically between the electrodes.The use of methodology of experiments design is one of this methods and present an original idea in high voltage prediction problems several factors were considered,namely the distance between electrodes and different parameters of the barrier such us is dimension and his holes.The experimental results are compared with results from numerical simulations.We firstly present the principals of this model then we apply it to the study of barrier effect. A good agreement has been found between the computed and experimental results

COVID19 : IS IT REALLY A THREAT TO CONTRACTUAL FREEDOM

  Abstract The concern of adapting the contract to the exceptional circumstances due to the pandemic obviously requires a common will of the parties to be in accordance with the theory of autonomy of the will. However, this is not always possible. The recourse to the judge is inevitable in the event of a disagreement. The legal process seems more predictibale given the legal standards of contract law.The article proposes legal mechanisms, referring to the guiding principles of common law and civil law, including good faith and the obligation to cooperate in mitigating the impact of coronavirus on the contractual standar

CONDITION FEMININE DANS LES THEORIES DE DEVELOPPEMENT

Le concept de développement peut être appréhendé comme « le processus par lequel les sociétés évoluent de manière à pouvoir satisfaire aux besoins fondamentaux de leur population » (François Perroux, 1964). C'est donc une modification qualitative de la société du point de vue économique, politique, social et culturel. Ainsi défini, le développement d'un pays sous-entend la participation de toute la population à tous les niveaux sans discrimination basée sur le sexe. Dès lors, il s'avère impossible de concevoir tout développement durable sans la participation des femmes. Mais comment la femme peut-elle contribuer au développement en s'impliquant dans la politique quand on sait que la politique est une réflexion concertée en vue de rechercher les voies et les moyens pouvant améliorer les conditions de vie de l'être humain ? (Malika Benrad, 2006).

Genotype and allele frequency of CYP2C19*17 in a healthy Iranian population

Background: Cytochrome P450 2C19 (CYP2C19) is important in metabolism of wide range of drugs. CYP2C19*17 is a novel variant allele which increases gene transcription and therefore results in ultra-rapid metabolizer phenotype (URM). Distribution of this variant allele has not been well studied worldwide. The aim of present study was to investigate allele and genotype frequencies of CYP2C19*17 in a healthy Iranian population and compare them with other ethnic groups. Methods: One hundred eighty healthy unrelated Iranian volunteer took part in this study and were genotyped for CYP2C19 *2, *3, *17 (-3402) by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and CYP2C19*17 (-806) by a nested-PCR assays. The distribution of CYP2C19*17 polymorphism in Iranian population was then compared with other ethnic groups. Results: The CYP2C19*17 allele frequency was 21.6 in Iranian population. Among studied subjects 5.5 were homozygous for CYP2C19*17 and phenotyped as ultra-rapid metabolizers; 28.8 were genotyped as CYP2C19*1*17 (extensive metabolizers) and 3.3 as CYP2C19*2*17 (intermediate metabolizers). Conclusion: The CYP2C19*17 genetic distribution in Iranian population is similar to Middle East or European countries. The high frequency of CYP2C19*17 in Iranian population highlights the importance of this new variant allele in metabolism of CYP2C19 substrates. Thus, future association studies are required to reveal clinical consequence of this genetic polymorphism in carrier individuals