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Preparation, <i>In-vitro, Ex-vivo</i>, and Pharmacokinetic Study of Lasmiditan as Intranasal Nanoemulsion-based <i>In Situ</i> Gel
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Background:

Lasmiditan (LAS) is a recently developed antimigraine drug and was approved in October, 2019 for the treatment of acute migraines; however, it suffers from low oral bioavailability, which is around 40%.

Objective:

This study aimed to improve the LAS bioavailability via formulation as nanoemulsionbased in situ gel (NEIG) given intranasally and then compare the traditional aqueous-LASsuspension (AQS) with the two successful intranasal prepared formulations (NEIG 2 and NEIG 5) in order to determine its relative bioavailability (F-relative) via using rabbits.

Method:

Two successfully prepared nanoemulsion (NE) formulas, a and b, were selected for the incorporation of different percentages of pH-sensitive in situ gelling polymer (Carbopol 934) to prepare NEIGs 1, 2, 3, 4, 5, and 6. The pH, gelation capacity, gel strength, and viscosity were predicted for the prepared NEIGs. The release (in vitro) and the nasal permeation (ex vivo) were determined for NEIG 2 and 5, and then both were subjected to pharmacokinetics in vivo studies. Eighteen male rabbits weighing 2.0 to 2.5 kg were employed in the parallel design study. The body surface area (BSA) normalization method was applied for LAS dose calculation. Serial blood samples were taken out and subjected to drug analysis using the HPLC method previously developed and validated by Kumar et al. Primary pharmacokinetics parameters, including maximum drug concentration in plasma (Cmax), time to reach C-max (T-max), and area under the concentration-time curve from time zero to affinity (AUCt0-∞) were calculated. Both NE (a and b), together with NEIG (2 and 5) formulas, were subjected to the stability study. Finally, a nasal ciliotoxicity study was carried out to evaluate the nasal toxicity of developed NEIGs 2 and 5.

Result:

The results showed that NEIGs 2 and 5 could be selected as the optimized NEIGs as both achieved 100% permeation within 20 min and then released within 25 and 35 min, respectively, thus achieving 3.3 folds with higher permeation percentages as compared to the AQS. Both NEIGs 2 and 5 exerted comparable release and permeation values as the corresponding NE a and b with more residence time in order to overcome the normal nasal physiological clearance. The values of C-max, Tmax, and AUC0- ∞ for NEIG 2 and NEIG 5 were 8066 ± 242 ng/ml, 0.75 ± 0.05 h, 19616.86 ± 589 ng. h/ml, and 7975.67 ± 239 ng/ml, 1.0 ± 0.05 h, 17912.36 ± 537 ng. h/ml, respectively, compared to the traditional AQS, which is equal to 4181.09 ± 125 ng/ml, 2 ± 0.2 h, and 8852.27 ± 266 ng. h/ml, respectively. It was discovered that NEIGs 2 and 5 had better intranasal delivery of LAS and could significantly (p < 0.05) achieve a higher value of permeability coefficient (3.3 folds) and 2.5 folds improvement in bioavailability when compared to AQS. The NE a, NE b, NEIG2, and NEIG5 formulations showed good stability at various temperatures. According to the nasal ciliotoxicity study, the nasal mucosal membrane, which was treated with NEIG 5, showed irritation with a bit of damage. However, damage was not observed when it was treated with NEIG 2, indicating the biocompatibility of the last one to be selected as the optimum formula.

Conclusion:

NEIG 2 and NEIG 5 are promising new intranasal formulas with a faster onset of action and greater bioavailability than the oral dosage form (AQS). Finally, the selected optimum gold formula that will be ready for further clinical study is NEIG 2.

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Publication Date
Fri Jan 01 2016
Journal Name
Journal Of Engineering
A Mathematical Model of a Thermally Activated Roof (TAR) Cooling System Using a Simplified RC-Thermal Model with Time Dependent Supply Water Temperature
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This paper presents a computer simulation model of a thermally activated roof (TAR) to cool a room using cool water from a wet cooling tower. Modeling was achieved using a simplified 1-D resistance-capacitance thermal network (RC model) for an infinite slab. Heat transfer from the cooling pipe network was treated as 2-D heat flow. Only a limited number of nodes were required to obtain reliable results. The use of 6th order RC-thermal model produced a set of ordinary differential equations that were solved using MATLAB - R2012a. The computer program was written to cover all possible initial conditions, material properties, TAR system geometry and hourly solar radiation. The cool water supply was considered time

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Publication Date
Sat May 01 2021
Journal Name
Journal Of Physics: Conference Series
Violet Laser Irradiation Effect on The Optical Properties of Cobalt oxide (CoO<sub>2</sub>) Thin Films deposited via Semi-Computerized Spraying System
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Abstract<p>The existing investigation explains the consequence of irradiation of violet laser on the optic properties of (CoO<sub>2</sub>) films. The film was equipped by the utilization of semi-computerized spray pyrolysis technique (SCSPT), it is the first time that this technique is used in the preparation and irradiation using a laser in this technique. From the XRD analysis, the crystalline existence with trigonal crystal system was when the received films were processed by continuous violet laser (405 nm) with power (1W) for different laser irradiation time using different number of times a laser scan (0, 6, 9, 12, 15 and 18 times) with total irradiation time(0,30,45,60,75,90 min</p> ... Show More
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Publication Date
Wed Jun 01 2016
Journal Name
Journal Of The College Of Languages (jcl)
Estructura y el análisis de los personajes en la novela“ Sotileza ” de José María de Pereda
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Resumen

    Sotileza , localismo santandrino de sutileza , es la parte más fina del aparejo de pescar donde va el anzuelo. Es la obra maestro de José María de Pereda.Su ambiente , el Santander viejo, anterior al año 50,evocado emocionadamente - emociόn romántica contenida en los trazos sobrios y firmes de un naturalism psicolόgico y paisajista,el Santander que el autor confiesa poseer en el fondo de su corazόn,«y tenerlo esculpido en la memoria de tal suerte que ,a ojos cerrados,me atrevería a trazarle con todo su perímetro y sus calles, y el color de sus piedras, y el número, y los nombres, y hasta las caras de sus habitantes».Dentro de la grandeza primaria de las criaturas de Pere

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Publication Date
Sun Mar 01 2020
Journal Name
Journal Of Colloid Interface Science
Corrigendum to “Organic acid concentration thresholds for ageing of carbonate minerals: Implications for CO2 trapping/storage” [J. Colloid Interface Sci. 534 (2019) 88–94]
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Erratum for Organic acid concentration thresholds for ageing of carbonate minerals: Implications for CO2 trapping/storage.

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Publication Date
Thu Apr 29 2021
Journal Name
Iraqi Journal Of Science
Synthesis, Molecular Structure from the X-ray Diffraction Data of the Powder (1E,1'E)-1,1'-(1,4-Phenylene)Bis(N-(Adamantan-1-yl)methanimine)
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The title compound was synthesized by 2:1 condensation between adamantan-1-ylamine and benzene-1,4- dicarbaldehyde in n-BuOH and produced a good yield 87% of new bis Schiff base. The compound skeleton was affirmed by FTIR, 1H NMR, LC-MS, and X-ray powder diffraction. The structure was solved by a parallel tempering process and refined by using Rietveld refinement. Two adamantan-1-ylimino groups are connected in the anti-positions to the planar central 1,4-dimethylbenzene group. All rings of the adamantyl group possess normal chair conformation.

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Publication Date
Thu Jul 01 2021
The spontaneous emission performance of a quantum emitter coupled to a hybrid plasmonic waveguide with specified output polarization for on-chip plasmonic single-photon source
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Publication Date
Tue May 11 2021
Journal Name
Photonics And Nanostructures - Fundamentals And Applications
The spontaneous emission performance of a quantum emitter coupled to a hybrid plasmonic waveguide with specified output polarization for on-chip plasmonic single-photon source
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Nowadays, most of the on-chip plasmonic single-photon sources emit an unpolarized stream of single photons that demand a subsequent polarizer stage in a practical quantum cryptography system. In this paper, we numerically demonstrated the coupling of the light emitted from a quantum emitter (QE) at 700 nm wavelength to the propagation mode supported by an on-chip hybrid plasmonic waveguide (HPW) polarization rotator. Our results proved that the light emitted is linearly polarized at 0º, 45º/−45º, and 90º with propagation lengths of 5 μm, 3.3 μm, and 3.9 μm, respectively. Moreover, high power-conversion efficiency was obtained from an applied transverse magnetic (TM) mode (0º-polarization) to a transverse electric (TE) (90º-polari

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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Comparison the effectiveness of using a magnetic field to control theColi phages isolated from rivulet water with water-treatment using magnetic field added iron filings
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The present study aimed to use the magnetic field and nanotechnology in the field of water purification, which slots offering high efficiency to the possibility of removing biological contaminants such as viruses and bacteria rather than the use of chemical and physical transactions such as chlorine and bromine, and ultraviolet light and boiling and sedimentation and distillation, ozone and others that have a direct negative impact on human safety and the environment. Where they were investigating the presence in water samples under study Coli phages using Single agar layer method and then treated samples positive for phages to three types of magnetic field fixed as follows (North Pole - South Pole - Bipolar) and compare the re

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Publication Date
Fri Jan 01 2021
Journal Name
Annals Of Tropical Medicine & Public Health
Newly developed method for determination of methyldopa drug using ammonium ceric (IV) nitrate by continuous flow injection analysis via homemade NAG-ADF-300-2 analyser
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A new, simple, sensitive and fast developed method was used for the determination of methyldopa in pure and pharmaceutical formulations by using continuous flow injection analysis. This method is based on formation a burgundy color complex between methyldopa andammonium ceric (IV) nitrate in aqueous medium using long distance chasing photometer NAG-ADF-300-2. The linear range for calibration graph was 0.05-8.3 mmol/L for cell A and 0.1-8.5 mmol/L for cell B, and LOD 952.8000 ng /200 µL for cell A and 3.3348 µg /200 µL for cell B respectively with correlation coefficient (r) 0.9994 for cell A and 0.9991 for cell B, RSD % was lower than 1 % for n=8. The results were compared with classical method UV-Spectrophotometric at λ max=280 n

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Publication Date
Wed Jan 01 2014
Journal Name
Journal Of The College Of Languages (jcl)
COMENTARIO ESTILÍSTICO- LITERARIO DE UN CUENTO DE JOSÉ ANTONIO GRILLO LONGORIA: “EL ALACRÁN Stylistic -Literary analysis of the story Jose Antonio Grillo Longoria: "The Scorpio"
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Al  comentar un texto literario no se llega solamente mediante el estudio de su Historia. Ese estudio sería vano, se convertiría en una simple memorización de datos, creo yo.
Comentar un texto supone comprobar las características generales de un movimiento, estilo de un autor... en otras palabras comprender con profundidad el texto literario en s
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