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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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Wed Mar 30 2022
Journal Name
Journal Of Educational And Psychological Researches
Realizing the personality traits of Bisha University Employees during the Covid-19 pandemic
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The post-Corona Covid-19 world is not the world before it, the problem of perception of personality traits with two axes: the characteristics of psychological and social compatibility, and the second aspect the mental disorder during the pandemic, and the accompanying precautions and prohibitions during the academic year 2020 AD. The aim of the research is to reveal the perception of the personal characteristics of Bisha University employees (students and faculty) during the Corona Covid-19 pandemic, and to reveal statistically significant differences in the perception of the personality traits of Bisha’s members during the Covid 19 according to the scientific qualification variables (female students -faculty members),  marital st

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Publication Date
Wed Dec 25 2019
Journal Name
Journal Of Engineering
Effect of Tail Regulators on Euphrates River Flood Capacity at Al Nassiriyah City
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Euphrates River extends about 125 km within the study area located in Annassiriyah City, Dhi Qar Governorate, Iraq. The impact of the seven hydraulic structures on the discharge capacity of the Euphrates River needs to be considered. The main objectives of this research are to increase the discharge capacity of Euphrates River within Annassiriyah City during flood seasons and study the impact of these hydraulic structures on the river capacity by using HEC-RAS 5.0.3 software. Five scenarios were simulated to study the different current condition of Euphrates River within Annassiriyah City. Other additional four scenarios were implemented through river training to increase the river capacity to 1300 m³/s; it is the flood

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Publication Date
Thu Aug 01 2024
Journal Name
Iop Conference Series: Earth And Environmental Science
Assessing the Environmental Footprint of the Cement Industry: A Pathway to Sustainable Development
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Abstract<p>Achieving a connection between sustainability processes and environmental protection, or what is known as sustainable development, requires paying more attention to environmental and sustainability issues for various projects and their effects on environmental problems. It involves determining the most appropriate ways to deal with them within pillars of sustainability (environmental, social, economic, and natural resources. As cement is a fundamental component of industrial services and construction in cities, it has a direct and significant interaction with the development process, making it one of the most important industries in Iraq. Because of the clinker particles and combustio</p> ... Show More
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Publication Date
Sun Jan 01 2017
Journal Name
Proceeding Of The 1st International Conference On Recent Trends Of Engineering Sciences And Sustainability
Design of a Fractional Order Sliding Mode Controller for Twin Rotor Aerodynamic System
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This paper proposes a new structure for a Fractional Order Sliding Mode Controller (FOSMC) to control a Twin Rotor Aerodynamic System (TRAS). The new structure is composed by defining two 3-dimensional sliding mode surfaces for the TRAS model and introducing fractional order derivative integral in the state variables as well as in the control action. The parameters of the controller are determined so as to minimize the Integral of Time multiplied by Absolute Error (ITAE) performance index. Through comparison, this controller outperforms its integer counterpart in many specifications, such as reducing the delay time, rise time, percentage overshoot, settling time, time to reach the sliding surface, and amplitude of chattering in control inpu

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Publication Date
Fri Sep 01 2017
Journal Name
Journal Of Baghdad College Of Dentistry
Assessing the Radiopacity of Three Resin Composite Materials Using a Digital Radiography Technique
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Background: Radiopacity is one of the prerequisites for dental materials, especially for composite restorations. It's essential for easy detection of secondary dental caries as well as observation of the radiographic interface between the materials and tooth structure. The aim of this study to assess the difference in radiopacity of different resin composites using a digital x-ray system. Materials and methods: Ten specimens (6mm diameter and 1mm thickness) of three types of composite resins (Evetric, Estelite Sigma Quick,and G-aenial) were fabricated using Teflon mold. The radiopacity was assessed using dental radiography equipment in combination with a phosphor plate digital system and a grey scale value aluminum step wedge with thickness

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Publication Date
Sun Jun 01 2014
Journal Name
Baghdad Science Journal
Synthesis of Some new 2-(4-Aryliminophenoxy)N-Arylacetamide Via p-hydroxy benzaldehyde.
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Publication Date
Sun Dec 01 2024
Journal Name
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Efficiency of SCL Via Google Classroom on Female Pre-service Teachers' Teaching Readiness
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This study intends to examine the efficiency of student-centered learning (SCL) through Google classroom in enhancing the readiness of fourth stage females’ pre-service teachers. The research employs a quasi-experimental design with a control and experimental group to compare the teaching readiness of participants before and after the intervention. The participants were 30 of fourth stage students at the University of Baghdad - College of Education for Women/the department of English and data were collected through observation checklist to assess their teaching experience and questionnaires to assess their perceptions towards using Google Classroom. Two sections were selected, C as a control group and D as the experimental one each with (

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Publication Date
Thu Aug 31 2017
Journal Name
Journal Of Engineering
Enhanced Performance of Consensus Wireless Sensor Controlled System via Particle Swarm Optimization Algorithm
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     This paper describes the application of consensus optimization for Wireless Sensor Network (WSN) system. Consensus algorithm is usually conducted within a certain number of iterations for a given graph topology. Nevertheless, the best Number of Iterations (NOI) to reach consensus is varied in accordance with any change in number of nodes or other parameters of . graph topology. As a result, a time consuming trial and error procedure will necessary be applied
to obtain best NOI. The implementation of an intellig ent optimization can effectively help to get the optimal NOI. The performance of the consensus algorithm has considerably been improved by the inclusion of Particle Swarm Optimization (PSO). As a case s

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Publication Date
Thu Jan 31 2019
Journal Name
Journal Of The College Of Education For Women
The Secret Reasons for the Western Scholars Studies The Biography of the prophet
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Western Scholars have criticized al the material on the point of reliability . Some have taken the unduly Sceptical view that nothing is to be trusted except Quran . The present study is based on opposing view that at least the material in the early biographers is to be accepted as true , except where there are particular reasons for thinking that an anecdote has been distorted ( or invented ) through legal or political motives. It is also assumed that most of the background material culled from a large number of vaired works , is sound . This standpoint .I would claim , leads to a coherent view of Muhammad's life and achievement.

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Publication Date
Wed Jan 01 2014
Journal Name
American Journal Of Mathematics And Statistics
Preliminary Test Single Stage Shrinkage Estimator for the Scale Parameter of Gamma Distribution
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