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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
Sun Dec 09 2018
Journal Name
Baghdad Science Journal
Application of Randomly Amplified Polymorphic DNA (RAPD) Technique to Estimate Genetic Distance among Some Methicillin Resistant Staphylococcus aureus Isolated from Different Iraqi Hospitals
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Methicillin resistant Staphylococcus aureus (MRSA) is one of the principal nosocomial causative agents. This bacterium has the capability to resist wide range of antibiotics and it is responsible for many diseases like skin, nose and wounds infection. In this study, randomly amplified polymorphic DNA (RAPD)-PCR was applied with ten random primers to examine the molecular diversity among methicillin resistant Staphylococcus aureus (MRSA) isolates in the hospitals and to investigate the genetic distance between them. 90 Isolates were collected from clinical specimens from Iraqi hospitals for a total of 90 isolates. Only 10 strains (11.11%) were found to be MRSA. From these 10 primers, only 9 gave clear amplification products. 91 fragment l

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Publication Date
Sat Sep 01 2007
Journal Name
Al-khwarizmi Engineering Journal
Free Convective Heat Transfer with Different Sections Lengths Placed at the Exit of a Vertical Circular Tube subjected to a Constant Heat Flux
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A free convective heat transfer from the inside surface of a uniformly heated vertical circular tube has been experimentally investigated under a constant wall heat flux boundary condition for laminar air flow in the ranges of RaL from 6.9108 to 5109. The effect of the different sections (restrictions) lengths placed at the exit of the heated tube on the surface temperature distribution, the local and average heat transfer coefficients were examined. The experimental apparatus consists of aluminum circular tube with 900 mm length and 30 mm inside diameter (L/D=30). The exit sections (restrictions) were included circular tubes having the same inside diameter as the heated tube but with different lengths of

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Publication Date
Wed Feb 27 2019
Journal Name
Journal Of Nano Research
A Specific NH&lt;sub&gt;3&lt;/sub&gt; Gas Sensor of a Thick MWCNTs-OH Network for Detection at Room Temperature
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NH3 gas sensor was fabricated based on deposited of Functionalized Multi-Walled Carbon Nanotubes (MWCNTs-OH) suspension on filter paper substrates using suspension filtration method. The structural, morphological and optical properties of the MWCNTs film were characterized by XRD, AFM and FTIR techniques. XRD measurement confirmed that the structure of MWCNTs is not affected by the preparation method. The AFM images reflected highly ordered network in the form of a mat. The functional groups and types of bonding have appeared in the FTIR spectra. The fingerprint (C-C stretch) of MWCNTs appears in 1365 cm-1, and the backbone of CNTs observed at 1645 cm-1. A homemade sensi

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Publication Date
Thu May 25 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Multipole Mixing Ratios of Gamma Rays From Fe(n,nγ) Fe 56 56 26 26  Reaction Using Constant Statistical Tensor Method (CST).
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The - Multiple mixing ratios of -transitions from levels of 56Fe populated in 56 56 ( , ) Fe n n Fe  ï‚¢ reactions are calculated by using const. S.T.M.  This method has been used in other works [3,7] but with pure transition or with  transitions that can be considered as pure transitionsØŒ in our work we used   This method for mixed  - transitions in addition to pure  - transitions. The experimental angular distribution coefficients a2 was used from previous works [1] in order to calculet - values. It is clear from the results that the - values are in good agreement or consistent, within associated errors, with those reported previously [1]. The discrepancies that occur

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Publication Date
Fri Jan 01 2010
Journal Name
Journal Of The College Of Languages (jcl)
Die Dimensionen der Kurzgeschichte”Steh auf, steh doch auf“ The Dimension of short story (wake, Wake) 1958 by the German writer, Heinrich Böll.
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In dieser Kurzgeschichte werden die Züge der Trümmerliteratur präzis dargestellt. Die wurde von Heinrich Böll im Jahr 1958 geschrieben. In der vorliegenden Arbeit konzentriere ich mich auf vielfältige Stoffe in Bezug auf die Lage nach dem Zweiten Weltkrieg. So gab ich dieser Arbeit einen besonderen Titel, der die Dimensionen dieser Kurzgeschichte heißt. Ich meine hier, die profunde Interpretation dieses Werkes, denn ich fand zwar hinter einigen Wörtern eine ganze Geschichte, die uns der Erzähler dadurch zeigen wollte.

So teilte ich diese Wörter (Grab, Schatten, Last, Schrei) als Dimensionen, von denen diese Arbeit umgekreist wird.

Diese Arbeit besteht aus vier Kapiteln, die aufeinander aufgebaut sind. Im ersten K

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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
Tue Sep 01 2020
Journal Name
Baghdad Science Journal
Uptake of Three Pharmaceuticals by Beans (Phaseolus vulgaris L.) from Contaminated Soils: امتصاص ثلاثة انواع من الادوية بواسطة نبات الفاصولياء في التربة الملوثة
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The ability of beans (Phaseolus vulgaris L.) to uptake three pharmaceuticals (diclofenac, mefenamic acid and metronidazole) from two types of soil (clay and sandy soil) was investigated in this study to explore the human exposure to these pharmaceuticals via the consumption of beans. A pot experiment was conducted with beans plants which were grown in two types of soil for six weeks under controlled conditions. During the experiment period, the soil pore water was collected weekly and the concentrations of the test compounds in soil pore water as well as in plant organs (roots, stems and leaves) were weekly determined.
The results showed that the studied pharmaceuticals were detected in all plant tissues; their concentration

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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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