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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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Tue Sep 07 2021
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Spatial variation of students in secondary school in Iraq for the 2006- 2011 period
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The research, whose goal was to study students' failure in secondary school in Iraq, found that 50% of the Iraqi governorates achieved the lowest student failure rates, and Baghdad governorate had the highest percentage of repeaters. And that half of the provinces in Iraq have males constitute 70% of the repeaters, and failure in the exam represented 79.7% of the reasons for failure, and that half of the students who failed are confined to the first and third intermediate grades at a rate of 51.9% , and the research revealed that the security instability was the most influential factor in Students fai

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Museum education is of great importance to an appropriate representation of museums’ collections and exhibits, including traditional fashion. Therefore, museum educators/curators need to be equipped with the most essential skills in their profession in order to adequately present the museum’s history and holdings. This could be achieved through specialized training programs. However, Arab countries are still behind in terms of museum education. Therefore, this article aims to shed light on this issue by assessing the knowledge and skills possessed by museum educators/curators and how training programs could affect them

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Tue Aug 30 2022
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Status of HBeAg in association with other baseline tests in Iraqi patients with CHB
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Chronic Hepatitis B(CHB) is a serious sequel after Hepatitis B Virus infection, although the rate of chronicity is inverse with age but it may be associated with a significant proportion of deaths related to cirrhosis and liver cancer. HBV serology and measurement of hepatocytic enzymes with viral load can predict disease prognosis and response to treatment. HBeAg refers to a high viral replication and associated with more infectivity to others. This study aimed to determine the impact of HBeAg status in chronically infected patients on various baseline tests. A total of 90 patients with CHB infection who were included in this study. Several standardized measures used for liver function tests, viral load and hepatitis B serological

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Publication Date
Thu Jun 25 2020
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The Prevalence of Potentially Inappropriate Prescribing in Geriatric Patients with Psychiatric Disorders in Iraq
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Potentially inappropriate prescribing is the prescribing of a medication that may cause more harm than benefit, the elderly population aged 65 years or older is more prone to potentially inappropriate prescribing because of alterations in their physiology, pharmacokinetics, and pharmacodynamics as well as polypharmacy and comorbidities, Beers list is a screening tool that help doctors to detect potentially inappropriate prescribing in geriatric patients and is designed to solve this problem, the aim of this study is to measure the prevalence of potentially inappropriate prescribing among psychiatric patients using the Beers criteria as an assessment tool and find the relationship between duration of hospitalization, comorbidities and pol

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Publication Date
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Investigation of several heavy metals in Al-Saddah agricultural drainage in Hilla city /Iraq
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Abstract<p>This study was done to determine the concentration of several heavy metals in the water of Al-Saddah agricultural drainage in Al-Saddah District in Babylon Province/Iraq. The concentrations of six heavy metals were measured (Pb, Cd, Cu, Hg, Fe, Zn). It was found that Pb concentration ranged from 0.06 mg/L at St.2 in autumn to 0.13 mg/L at St.2 in winter. Fe concentrations ranged from 0.04 mg/L at St.2 in autumn and winter to 0.41 at St.2 in Summer. Cd concentrations ranged from 0.008 mg/L at St.2 in summer to 0.05 mg/L at St.2 in winter. Cu concentrations ranged from 0.01 mg/L at St.1 in both autumn and winter to 0.63 mg/L at St.2 in winter. Hg concentrations was ranged from 0.002 mg/</p> ... Show More
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Publication Date
Wed Mar 16 2016
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THE CAUSES OF THE PHENOMENON OF MARKETING DECEPTION AND ITS IMPACT IN THE AREAS OF CONSUMER PROTECTION/ SEARCH EXPLORATORY OF THE CONSUMERS PERSPECTIVE: THE CAUSES OF THE PHENOMENON OF MARKETING DECEPTION AND ITS IMPACT IN THE AREAS OF CONSUMER PROTECTION/ SEARCH EXPLORATORY OF THE CONSUMERS PERSPECTIVE
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The research aims to diagnose the causes of the phenomenon of Marketing deception catalog, which is now deployed in the Iraqi market and related to producers and marketers, consumers, regulators and other institutions) and their impact in the areas of prejudice to the consumer protection (product and signifying specifications, price, advertising, packaging), as well as identify differences in the sample responses according to personal variables, it has been the adoption of the resolution as a tool to collect data and information through a sample survey of consumer opinions totaling 108 people in shopping centers in the province of Baghdad and in the Karkh and Rusafa, It was the use of methods selected statistical represented by the arith

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Publication Date
Wed Mar 16 2022
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The Effectiveness of a Selective Counseling Program in Modifying the Irrational Thoughts That Cause Anger in a Sample of Female Teachers in Different Educational Stages
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Publication Date
Thu Dec 01 2011
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Dynamic algorithm (DRBLTS) and potentially weighted (WBP) to estimate hippocampal regression parameters using a techniqueBootstrap (comparative study)
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Bootstrap is one of an important re-sampling technique which has given the attention of  researches recently. The presence of outliers in the original data set may cause serious problem to the classical bootstrap when the percentage of outliers are higher than the original one. Many methods are proposed to overcome this problem such  Dynamic Robust Bootstrap for LTS (DRBLTS) and Weighted Bootstrap with Probability (WBP). This paper try to show the accuracy of parameters estimation by comparison the results of both methods. The bias , MSE and RMSE are considered. The criterion of the accuracy is based on the RMSE value since the method that provide us RMSE value smaller than other is con

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