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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 Feb 26 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Use the Style of the Activity Based Cost time Drivine (TDABC) and its Impact on the Untapped Resources: Empirical study in the General Company for Textile Industries - Wasit
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   The research aims to identify the importance of using the style of the cost on the basis of activity -oriented in time TDABC and its role in determining the cost of products more equitably and thus its impact on the policy of allocation of resources through the reverse of the changes that occur on an ongoing basis in the specification of the products and thus the change in the nature and type of operations . The research was conducted at the General Company for Textile Industries Wasit / knitting socks factory was based on research into the hypothesis main of that ( possible to calculate the cost of activities that cause the production through the time it takes to run these activities can then be re- distributed product cost

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Publication Date
Sun Dec 01 2019
Journal Name
Al-ustath Journal For Human And Social Sciences
Landscape as History: A Postcolonial Ecopoetic Study of the Poetry of Derek Walcott
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Abstract: As human history is implicated in landscape or the natural history, it can be stated that the origins of the Caribbean writers' conflict, in general, are the colonial history of West India. That history which tells the story behind not only their fragmented identity, but also the problems connected to their language as well. Building on the arguments of the prominent Postcolonial ecoccritics such as Elizabeth DeLoughrey, George Handley, Helen Tiffin, and Graham Huggan, this research analyzes selected poems by Derek Walcott's which are bounded in his volume, Collected Poems. It shows how the Caribbean history has been erased due to the brutality of colonization offering landscape as a reliable source which has recorded that history

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Publication Date
Wed May 24 2017
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
PREPARATION CONCETRATE PROTEIN FROM AL- ZAHDI DATE’S PITS AND USED FOR BISCUIT FORTIFICATION: PREPARATION CONCETRATE PROTEIN FROM AL- ZAHDI DATE’S PITS AND USED FOR BISCUIT FORTIFICATION
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This study was conducted to prepare protein concentrates from AL-Zahdidate’s pits by using alkaline methods where the chemical composition of the pits were (7.30, 1.04, 5.80, 8.68 and 77.19) % for each of the moisture, ash, protein, fat and carbohydrates respectively and the chemical composition of the concentrate protein was (6.62, 4.10, 26.70, 0.93, and 58.65) % respectively. The content of protein concentrate from the metallic elements (144.07, 25.11, 15.02, 0.49, 0.59, 0.27, 0.22 and 234.6) mg/ 100 g each of potassium, magnesium, calcium, iron, manganese, copper, zinc and phosphorus respectively. The results of SDS-PAGE showed five bands with weights molecular ranged between 11000-70000 Dalton. Give the biscuit which contain protei

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Publication Date
Sat Jan 28 2012
Journal Name
Rafidain Journal Of Science
Photodynamic Effect on Photosensitized Candida albicans with Hematoporphyrin Derivative Using Low Power Diode Laser In Vitro
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Publication Date
Sun May 01 2016
Journal Name
Iraqi Journal Of Science
Efficient text in image hiding method based on LSB method principle
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The steganography (text in image hiding) methods still considered important issues to the researchers at the present time. The steganography methods were varied in its hiding styles from a simple to complex techniques that are resistant to potential attacks. In current research the attack on the host's secret text problem didn’t considered, but an improved text hiding within the image have highly confidential was proposed and implemented companied with a strong password method, so as to ensure no change will be made in the pixel values of the host image after text hiding. The phrase “highly confidential” denoted to the low suspicious it has been performed may be found in the covered image. The Experimental results show that the covere

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Publication Date
Sun Mar 12 2023
Journal Name
المجلة الدولية للتنمية في العلوم الاجتماعية والإنسانية
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One of the most important features of American foreign activity during the second half of the 19th century was the encouragement of sending Protestant missionary missions to all countries around the world. The mission of these missions was facilitated by the weakened state of the Ottoman Empire, the increasing influence of European countries, and their interference in its internal affairs. Despite the Ottoman efforts to counter the activities of these missions, the American missionary missions adopted a well-planned strategy that suited the conditions of the region, aimed at achieving their goals through direct and indirect methods, including intervention in the field of education. These missions gave great importance to educational aspects

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Publication Date
Tue Oct 01 2024
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A comprehensive review on the use of Ti3C2Tx MXene in membrane-based water treatment
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Publication Date
Sun Jun 01 2014
Journal Name
Baghdad Science Journal
Preparation, Characterization & Biological activity for Some Iron(II) Complexes Containing Mixed Ligands (Benzilazine & Semicarbazone) & Study of Laser Effect on Them
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The research included preparation of new iron(II) complexes with mixed ligands including benzilazine(BA) and semicarbazone ligands {benzilsemicarbazone- BSCH or benzilbis(semicarba-zone)- BBSCH2 or salicylaldehydesemicarbazone- SSCH2 or benzoinsemicarbazone- B'SCH2}.by classical and microwave methods. The resulted complexes have been characterized using chemical and physical methods. The study suggested that the above ligands form ionic complexes having formulae [Fe(SCHi)(BA)(Cl)m](Cl)2-m {where SCH, BSCH, BBSCH2, SSCH¬2 or B'SCH2 ligands; m=1 or 2}. Hexacoordinated mononuclear complexes have been investigated by this study and having octahedral geometries. The effect of laser ray type visible region have been studied on solid ligands and

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Publication Date
Tue Nov 09 2021
Journal Name
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The Effect Of Time Driven Activity Based Costing in Pricing Decisions
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The research aims to demonstrate the impact of TDABC as a strategic technology compatible with the rapid developments and changes in the contemporary business environment) on pricing decisions. As TDABC provides a new philosophy in the process of allocating indirect costs through time directives of resources and activities to the goal of cost, identifying unused energy and associated costs, which provides the management of economic units with financial and non-financial information that helps them in the complex and dangerous decision-making process. Of pricing decisions. To achieve better pricing decisions in light of the endeavor to maintain customers in a highly competitive environment and a variety of alternatives, the resear

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Publication Date
Sun Aug 01 2021
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Simulation based comparison of routing protocols in wireless multihop adhoc networks
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Routing protocols are responsible for providing reliable communication between the source and destination nodes. The performance of these protocols in the ad hoc network family is influenced by several factors such as mobility model, traffic load, transmission range, and the number of mobile nodes which represents a great issue. Several simulation studies have explored routing protocol with performance parameters, but few relate to various protocols concerning routing and Quality of Service (QoS) metrics. This paper presents a simulation-based comparison of proactive, reactive, and multipath routing protocols in mobile ad hoc networks (MANETs). Specifically, the performance of AODV, DSDV, and AOMDV protocols are evaluated and analyz

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