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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
Tue Jun 01 2021
Journal Name
Iraqi Journal Of Physics
Studying Audio Capacity as Carrier of Secret Images in Steganographic System
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Steganography art is a technique for hiding information where the unsuspicious cover signal carrying the secret information. Good steganography technique must be includes the important criterions robustness, security, imperceptibility and capacity. The improving each one of these criterions is affects on the others, because of these criterions are overlapped each other.  In this work, a good high capacity audio steganography safely method has been proposed based on LSB random replacing of encrypted cover with encrypted message bits at random positions. The research also included a capacity studying for the audio file, speech or music, by safely manner to carrying secret images, so it is difficult for unauthorized persons to suspect

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Publication Date
Wed Oct 09 2019
Journal Name
Journal Of The College Of Education For Women
Silence as a Means of Communication in Harold Pinter’s The Caretaker
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Harold Pinter’s The Caretaker(1959) clearly portrays a lack of communication among the characters of the play which refers to the condition of modern man. This failure of communication led Harold Pinter to use a lot of pauses and silences in all the plays he wrote instead of words. Samuel Beckett preceded Pinter in doing so in his plays and one way to express the bewilderment of modern man during the 20th century is through the use of no language in the dramatic works. Language is no more important to modern man; instead, he uses silence to express his feelings. Silence is more powerful than the words themselves. That’s why long and short pauses can be seen throughout all Pinter’s plays.

In this play, th

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Publication Date
Wed Jul 06 2022
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Using of costs based on activity that focused on performance in Reduce Costs and their reflection to improve competitive advantage: An applied research in wasitTextile and Knitting factory
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The research aims mainly to the role of the statement style costs on the basis of activity based on performance (PFABC) to reduce production cost and improve the competitive advantage of economic units and industrial under the modern business environment dominated by a lot of developments and changes rapidly, which necessitates taking them and criticize them to ensure survival and continuity.  The research problem is the inability of traditional cost methods of providing useful information to the departments of units to take many administrative decisions, particularly decisions related to the product and calculating the costs of the quality of the sound and the availability of the need and the ability to replace methods capa

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Publication Date
Sun Aug 25 2024
Journal Name
University Of Samarra
Preparation, diagnosis and testing of the biological ‎activity of new complexes of Schiff bases
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‎ Sixteen new complexes with the general formula [M(L)2(H2O)2] were ‎prepared resulting from the reaction of the two new Schiff base ligands, which ‎are‏: -‏ L1= (E)-5-((2-hydroxybenzylidene)amino)-2-phenyl-2,4-dihydro-3H-pyrazol-3-one)‎ L2 = (E)-5-((2-hydroxy-3-methoxybenzylidene)amino)-2-phenylpyrazolidin-3-one) ‎ ‎ With divalent metal ions (manganese, cobalt, nickel, copper, zinc, cadmium, ‎mercury) and (tetravalent platinum).‎‏ ‏ ‎ Ligands was derived from the reaction of the amine (5-amino-2-phenyl-2,4-‎dihydro-3H-pyrazol-3-one) with Salicylaldehyde and ortho-vanillin, which is ‎linked to the metal ions via the nitrogen atoms are the isomethene group and ‎the oxygen is the hydroxide group of t

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Publication Date
Tue Mar 01 2011
Journal Name
Journal Of Economics And Administrative Sciences
The impact of cognitive processes in the areas of organizational changeApplied Study in the Directorate General of Training and Development / Ministry of Electricity
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Centric study on the interest of the Directorate General of Training and Development / Ministry of Electricity to consolidate the concept of process and enhancement of knowledge in the areas of organizational change، it reached a sample of the study (44) people who are highly heads of departments، technicians and administrators in different sections of the Directorate and by using the correlation coefficient (Spearman) & coefficient of simple regression been tested correlations between variables and the impact of the study، as has been reached to integrate the role of cognitive processes with the areas of organizational change and relationships that were significant at the level of overall dimensions and subsidiary organs.

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Publication Date
Sat Dec 30 2023
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Interpretation of Mud Losses in Carbonates Based on Cuttings Description, Well-Logging, Seismic and Coherency Data
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    Hartha Formation is an overburdened horizon in the X-oilfield which generates a lot of Non-Productive Time (NPT) associated with drilling mud losses. This study has been conducted to investigate the loss events in this formation as well as to provide geological interpretations based on datasets from nine wells in this field of interest. The interpretation was based on different analyses including wireline logs, cuttings descriptions, image logs, and analog data. Seismic and coherency data were also used to formulate the geological interpretations and calibrate that with the loss events of the Hartha Fm.

   The results revealed that the upper part of the Hartha Fm. was identified as an interval capable of creating potentia

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Publication Date
Sat Feb 01 2025
Journal Name
Iop Conference Series: Earth And Environmental Science
Chitosan as an Aflatoxin Inhibitor in Local Fish Feed
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Abstract<p>The current research attempts to find a feed additive that enhances fish growth and eliminate toxins generated from fungi and mold, which are found in improperly manufactured and stored feed, while ensuring the safety of these fish meat for the consumer. Therefore, the organic properties of chitosan powder were examined in order to determine its impact on maturation of young <italic>Cyprinus carpio</italic>. Chitosan was tested in three samples of feedings at three concentrations: CH1 7gm/1kg fish feed, CH2 10gm/1kg, and CH3 15gm/1kg carp fish feed. The results showed that the third parameter, 15gm CH3 chitosan/kg of feed, was superior to the other parameters, having a highl</p> ... Show More
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Publication Date
Mon Mar 01 2010
Journal Name
Al-khwarizmi Engineering Journal
Synthetic Sacks as Reinforced Fibers in the Thermosetting Composites
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This study was carried out to investigate the preparation of thermosetting polymeric blend consisting of three adhesive types, namely: epoxy, polyvinyl formal (PVF) and unsaturated polyester. Both of epoxy and PVF were used as a matrix-binder at fixed weight. Whilst unsaturated polyester was used at different weights and added to the matrix so as to produce prepared epoxy-PVF-unsaturated polyester blend. Several experiments were performed at different operating conditions, mixing speed and time at room temperature to identify the most favorable operating conditions. The optimum mixing speed and mixing time for the prepared blend were 500rpm and 5 minutes respectively.

      Solid wastes-synthetic sack fib

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Publication Date
Thu Jul 13 2023
Journal Name
International Journal Of Research In Social Sciences &amp; Humanities
Subject Review: Blogs as Learning Tools in EFL Classrooms
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Blogs have emerged as a powerful technology tool for English as a Foreign Language (EFL) classrooms. This literature review aims to provide an overview of the use of blogs as learning tools in EFL classrooms. The study examines the benefits and challenges of using blogs for language learning and the different types of blogs that can be used for language learning. It provides suggestions for teachers interested in using blogs as learning tools in their EFL classrooms. The findings suggest that blogs are a valuable and effective tool for language learning, particularly in promoting collaboration, communication, and motivation.

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Crossref
Publication Date
Wed Jan 01 2014
Journal Name
Journal Of The College Of Languages (jcl)
Tennessee Williams: Memories as symbols in The Glass Menagerie
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The Glass Manegerie is a metaphor, which is one of the greatest plays  of great writer Williams. The play talks about  the poor people in society and how try to escape this group of people from the real world to get rid of the hardness of this tuff reality and live in a fantasy world that is much like the glass where the world is very weak this world is acting by Laura, she is  owner of these animals breakable glass where it's weak and unable to defend itself as well as the mother Amanda  is a very selfish never think about her children but only herself.

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