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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
Sat Jun 01 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The contribution of e-banking to the competitive advantage of banking institutions in Algeria: Case Study of Agricultural and Rural Development Bank
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The importance of the study stems from the fact that it deals with a very important subject, namely, the pivotal role played by E-banking in achieving the competitive advantage of the banking institutions operating in Algeria. By adopting the banking institution and adopting the elements of the electronic marketing mix and developing it as required by the environment The banking system of developments will inevitably be able to achieve excellence from its competitors as each of these elements have an important role in achieving competitive advantage, we relied in this study on studies and research that directly affect the problem of the study and we have put Estep In order to activate the contribution of e-banking in achieving competitiv

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Publication Date
Sun Dec 02 2018
Journal Name
Journal Of The College Of Education For Women
The Role of Local Satellite Channels in the formation of knowledge and trends of the Iraqi Public Towards Terrorism: A Field Study
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Terrorism is a global phenomenon that engulfs most regions of the world to varying degrees. Media outlets are aware of the many incidents of violence and terrorism that have increased in recent times. The differences between the size of the phenomenon in different societies are the causes and severity of the phenomenon. On the role of local satellite channels in shaping the knowledge and trends of the Iraqi public towards the events of terrorism, in light of the assumptions of reliance on the media. The importance of this study is that it assesses the role of local satellite channels in the formation of knowledge and trends The study seeks to know the extent of exposure of the Iraqi public to local satellite channels, and to reveal the e

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Publication Date
Sun Dec 07 2014
Journal Name
Baghdad Science Journal
A Study Of Corrosion Behavior Of Low Carbon Steel In Acidic And Basic Washing Water Of Crude Oil Solution At Different Temperatures
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The corrosion behavior of low carbon steel in washing water of crude oil solution has been studied potentiostatically at five temperatures in the range ( 303 –343 )K, at pH ( 4 ) and at pH (4,6,7,9,11 ) at (343K)..The corrosion potential shifted to more negative values with increasing temperature and the corrosion current density increased with increasing temperature, the corrosion current density (icorr) decreased with increasing pH in the rang ( 4 – 7 ) and it increased with increasing pH in the rang ( 9 – 11 ) at ( 343 K ), while the corrosion potential generally variation with increasing pH in the rang (4-11)at(343K. From the general results for this study can be seen that thermodynamic and kinetic function were

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Publication Date
Thu Oct 18 2018
Journal Name
Al–bahith Al–a'alami
The Pressures Affecting the Performance of Iraqi Media before the Legislative Elections of 2018 (Iraqi Satellite News Channel- as a Model): A Survey Study  Dr.Safad Husam Hammody
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The modernity of election practices of the elections in Iraq, according to the democratic approach, has led to a struggle between political rival forces reflecting a deep pressure on the tools involved in the management, marketing or control of these elections across the general social level. Hence the problem of research resides in answering the following question: What is the nature and size of the pressures affecting the media performance of Al-Iraqia News channel before the legislative elections of 2018 in Iraq?
      The objectives of the research were the following:
1. to identify the nature of the pressures that limit the Al-Iraqia News channel’s perfo

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Publication Date
Wed Jan 01 2020
Journal Name
Iraqi Journal Of Science
Paper based glucose biosensor depending on SPCE modified with hemoglobin and silver nanoparticles
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The direct electron transfer behavior of hemoglobin that is immobilized onto screen-printed carbon electrode (SPCE) modified with silver nanoparticles (AgNPs) and chitosan (CS) was studied in this work. Cyclic voltametry and spectrophotometry were used to characterize the hemoglobin (Hb) bioconjunction with AgNPs and CS. Results of the modified electrode showed quasi-reversible redox peaks with a formal potential of (-0.245 V) versus Ag/AgCl in 0.1 M phosphate buffer solution (PBS), pH7, at a scan rate of 0.1 Vs-1. The charge transfer coefficient (α) was 0.48 and the apparent electron transfer rate constant (Ks) was 0.47 s-1. The electrode was used as a hydrogen peroxide biosensor with a linear response over 3 to 240 µM and a detection li

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Publication Date
Mon Dec 03 2018
Journal Name
Association Of Arab Universities Journal Of Engineering Sciences
Condition assessment and rehabilitation for trunk sewer deterioration based on Semi-Markov model
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An accurate assessment of the pipes’ conditions is required for effective management of the trunk sewers. In this paper the semi-Markov model was developed and tested using the sewer dataset from the Zublin trunk sewer in Baghdad, Iraq, in order to evaluate the future performance of the sewer. For the development of this model the cumulative waiting time distribution of sewers was used in each condition that was derived directly from the sewer condition class and age data. Results showed that the semi-Markov model was inconsistent with the data by adopting ( 2 test) and also, showed that the error in prediction is due to lack of data on the sewer waiting times at each condition state which can be solved by using successive conditi

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Publication Date
Mon Jan 01 2024
Journal Name
Fifth International Conference On Applied Sciences: Icas2023
Facial deepfake performance evaluation based on three detection tools: MTCNN, Dlib, and MediaPipe
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Publication Date
Thu Dec 01 2022
Journal Name
Journal Of Engineering
Deep Learning-Based Segmentation and Classification Techniques for Brain Tumor MRI: A Review
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Early detection of brain tumors is critical for enhancing treatment options and extending patient survival. Magnetic resonance imaging (MRI) scanning gives more detailed information, such as greater contrast and clarity than any other scanning method. Manually dividing brain tumors from many MRI images collected in clinical practice for cancer diagnosis is a tough and time-consuming task. Tumors and MRI scans of the brain can be discovered using algorithms and machine learning technologies, making the process easier for doctors because MRI images can appear healthy when the person may have a tumor or be malignant. Recently, deep learning techniques based on deep convolutional neural networks have been used to analyze med

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Publication Date
Thu Jun 01 2023
Journal Name
Journal Of Engineering
On the Laser Micro Cutting: Experimentation and Mathematical Modeling based on RSM-CCD
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The laser micro-cutting process is the most widely commonly applied machining process which can be applied to practically all metallic and non-metallic materials. While this had challenges in cutting quality criteria such as geometrical precision, surface quality and numerous others. This article investigates the laser micro-cutting of PEEK composite material using nano-fiber laser, due to their significant importunity and efficiency of laser in various manufacturing processes. Design of experiential tool based on Response Surface Methodology (RSM)-Central Composite Design (CCD) used to generate the statistical model. This method was employed to analysis the influence of parameters including laser speed,

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Publication Date
Wed Sep 01 2021
Journal Name
Baghdad Science Journal
Coronavirus Disease Diagnosis, Care and Prevention (COVID-19) Based on Decision Support System
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              Automated clinical decision support system (CDSS) acts as new paradigm in medical services today. CDSSs are utilized to increment specialists (doctors) in their perplexing decision-making. Along these lines, a reasonable decision support system is built up dependent on doctors' knowledge and data mining derivation framework so as to help with the interest the board in the medical care gracefully to control the Corona Virus Disease (COVID-19) virus pandemic and, generally, to determine the class of infection and to provide a suitable protocol treatment depending on the symptoms of patient. Firstly, it needs to determine the three early symptoms of COVID-19 pandemic criteria (fever, tiredness, dry cough and breat

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