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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
Fri Jan 01 2016
Journal Name
Journal Of Computer And Communications
Pathfinding in Strategy Games and Maze Solving Using A* Search Algorithm
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Publication Date
Sun Mar 03 2024
Journal Name
Mesopotamian Journal Of Cybersecurity
Using Information Technology for Comprehensive Analysis and Prediction in Forensic Evidence
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With the escalation of cybercriminal activities, the demand for forensic investigations into these crimeshas grown significantly. However, the concept of systematic pre-preparation for potential forensicexaminations during the software design phase, known as forensic readiness, has only recently gainedattention. Against the backdrop of surging urban crime rates, this study aims to conduct a rigorous andprecise analysis and forecast of crime rates in Los Angeles, employing advanced Artificial Intelligence(AI) technologies. This research amalgamates diverse datasets encompassing crime history, varioussocio-economic indicators, and geographical locations to attain a comprehensive understanding of howcrimes manifest within the city. Lev

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Publication Date
Tue Jan 02 2007
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Beta-Carotene, Glycemic Control And Dyslipidemia In Type 2 Diabetes Mellitus
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Background : Diabetes mellitus is a stressful condition in which the increased production of free radicals impairs the generation of naturally occurring antioxidants like vitamins and
carotenoids . 
Aim :The present study deals with the changes in serum ß-carotene in type 2 diabetes mellitus, as modulated by glycemic control and oxidative stress .
Subjects & methods : Multiple biochemical parameters were obtained from plasma of 57 patients with type 2 diabetes mellitus ( 25 males and 32 females ) , on oral hypoglycemic with
a disease duration of 1- 15 years and 37 healthy normal subject s of matching age and sex to serve as controls. The biochemical parameters measured in the present study i

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Publication Date
Sun Jan 01 2017
Journal Name
Journal Of Central European Agriculture
Seed priming effect on field emergence and grain yield in sorghum
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Most cultivars of sorghum have low field emergence as common problem. Three experiments were carried out at Agriculture College, Baghdad University. First experiment was conducted in laboratory according to Complete Randomized Design (CRD) with four replicates. Second and third experiments were conducted at field according to Randomized Complete Block Design (RCBD) during the spring and the fall seasons of 2015, respectively, with four replicates for each one. Same two factors were studied at each experiment. First factor was seed priming by seed soaking for 10 hours in distilled water, solvents of GA3, KCl and thiamine (300, 40 and 30 mg*L-1, respectively) and non-primed seed. Second factor was three cultivars of sorghum (Inqath, Kafier an

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Publication Date
Sun Dec 10 2017
Journal Name
Al-academy
Building aesthetic and expressive long shot in the film contemporary novelist
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The research deals with an important detail of the joints of the film industry and television drama, which is the expression and aesthetic of the long shot, after being popularized by some directors, and that the long shot has been employed since the beginning of the cinema. But the research addresses the contemporary film and how the long shot worked. The researcher identified her goal in identifying the aesthetic and expressive of the long shot in the contemporary film, and then defined the term of the shot and the long shot.
The theoretical framework was based on two topics: the first (aesthetic and artistic expression in cinema) and the second (the long shot and the state of its construction). The researcher then chose LA LA LAND

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Publication Date
Sun Mar 15 2020
Journal Name
Journal Of The College Of Education For Women
Shatt Al-Gharraf in Ancient and Modern Maps: سالار علي خضر
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This research aims to shed light on the geography of Shatt Al-Gharraf, one of the main branches of the Tigris River south of the sedimentary plain, where the changes exposed by this Shatt (river) were followed by a set of old and modern maps, which date back to the years(3000 BC, 1771 AD, 1810 AD, 1944 AD, 1959 AD, 2009 AD, 2017 AD).Through this research, Shatt al-Gharrafwas found to be an integrated river in terms of the geomorphological phenomena of the rivers (river meanders, river islands, marshes, and estuary). Besides, it was exposed to several changes especially itsdownstream in the Euphrates. It was previously flowing into the Euphrates but due to a number of factors such as the shortage of water in the Tigris River in recent yea

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Publication Date
Sat Dec 30 2023
Journal Name
Journal Of The College Of Education For Women
Shyness in Female College Students And its relation to some Variables
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The human being is a social being and human communication is a fundamental axis in the process of social interaction, and the characteristic of social shyness grows through the interaction of the individual with his environment. Identifying the level of shyness among university students, and identifying the differences in shyness among university students according to specialization (scientific, humanities). In order to achieve the objectives of the research, the researcher prepared a measure of shyness based on Zimbardo's theory, and the components that he identified are the (behavioral, cognitive, and emotional components). The validity and reliability were calculated using the Cronbach's alpha method, reaching (0.94), and the scale in

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Publication Date
Thu Dec 29 2016
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Serumleptin, Triglycerides, Cholestrol and Hdl- Cholestrol In Non Dlabetic Obese Subjects
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         This study was carried out to investigate the relationship between Serum leptin, Body Mass Index (BMI), Triglycerides, Cholesterol and HDL- Cholesterol in Non Diabetic Obese subjects comparing with healthy subject. A 36 male and female Iraqis obese were studied, mean age 50.1, 43.3 years respectively and 23 healthy subjects. Serum leptin, Triglycerides, Cholesterol and HDL- Cholesterol were measured. Leptin, Triglycerides, Cholesterol, HDL- Cholesterol and BMI significantly increased in obese males and females compared with control, but there was no significant difference in HDL- Cholesterol and BMI when compared between obese males and females. A low significant positive correlation was f

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Publication Date
Sun Jan 01 2012
Journal Name
Journal Of The College Of Languages (jcl)
Difficulties Faced by Engineering Students in Reading and Comprehending English Texts
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Reading is an interactive process that goes on between the reader and the text, resulting in comprehension. The text presents letters, words, sentences, and paragraphs that encode meaning. The reader uses knowledge, skills, and strategies to determine what that meaning is. Reading comprehension is much more than decoding; it results when the reader knows which skills and strategies are appropriate for the type oftext, and understands how to apply them to accomplish the reading purpose.Reading comprehension is important because without it reading is nothing more than tracking symbols on a page with your eyes and sounding them out leaving the reader with no information. Instead of promoting traditional approaches, reading should be ta

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Publication Date
Tue Dec 21 2021
Journal Name
Journal Of Legal Sciences
The World Health Organization and its international responsibility in facing epidemics
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The spread of COVID-19 virus over the world had affected all aspects of life on the earth. This had led to investigating the role of the specialized international organizations like the World Health Organization (WHO) , specially after the criticisms for its performance during this pandemic.

This study tries to explore the principles upon which the WHO responsibility was proposed and whether the criticisms and accusations for it are true.

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