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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
Mon Apr 04 2022
Journal Name
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Stressful Life Events and their Relationship to Life Skills in Middle School Students
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The current research aims to identify the stressful life events among middle school students in terms of gender (male-female), academic branch (scientific-literary), and the Life Skills of the students of the preparatory stage in terms of gender (male-female), and academic branch (scientific-literary). Additionally, the study aims to identify the relationship between stressful life events and life skills in middle school students. A sample of (200) students who were selected randomly from the Directorate of education of Baghdad Karkh/ III was used in this study. To achieve the objectives of the current research, the researcher has adopted two scales, the stressful life events scale for the researcher Al-Sultan (2008), and the life skills

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Publication Date
Mon Sep 03 2018
Journal Name
Al-academy
Integrative Relationship between the Picture and the Written Text in the Commercial Advertisement
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Publication Date
Fri Jan 01 2010
Journal Name
Al Adab Journel
Gender Struggle and Women's Predicament in Tennessee Williams' A Street Car named Desire
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Abstract The aim of this paper is to shed light on the theme of Gender Struggle and Women’s Predicament in Tennessee Williams’ A Street Car Named Desire .The paper tries to show William's dealings with the critical social themes like Men's Brutality and women's predicament. The paper exposes the complete shift of the balance of power between the genders in America after the two world wars. Williams illustrates society’s changing attitudes towards masculinity and denounces the society's attitudes towards women in America at that time. He rebels against the cruelty of the modern age and regrets the disintegration of the values of the south and their being replaced by the disruptive forces of modern life. In the end of the play, brutalit

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Publication Date
Fri Mar 01 2013
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Experimental Parasitology
An Acanthamoeba castellanii metacaspase associates with the contractile vacuole and functions in osmoregulation
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Publication Date
Mon Jun 08 2020
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COVID-19 clinical characteristics and outcomes in 60 hospitalized Iraqi patients -Case series
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Publication Date
Thu Jan 20 2022
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Information Sources and their Role in E-learning from Iraqi College Students’ Viewpoint
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The study aims at identifying the sources of information and explaining their role in e-learning from the viewpoint of the Iraqi college students. The researchers relied on the descriptive method of the survey method to collect data and know the point of view of undergraduate students from the Department of Information in the College of Arts / Tikrit University and the Department of Quranic Studies at the College of Arts / University of Baghdad. The questionnaire was used as an instrument of the study, the research sample is (120) students; each section has (60) male and female students. The study concluded that there are many types and forms of information sources that students receive through electronic educational platforms from text con

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Publication Date
Tue Jul 01 2014
Journal Name
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Serum Leptin levels in ovarian polycystic disease and its correlation to body weight
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Publication Date
Wed Sep 28 2022
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Women's Rape in Iraq between Legislation and Social Norms: A Critical Discourse Analysis
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Fri May 01 2020
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Methotrexate effect on obestatin, progranulin and kidney function in RA Iraqi males patients
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Publication Date
Mon Dec 05 2022
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A Security and Privacy Aware Computing Approach on Data Sharing in Cloud Environment
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