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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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Sun Dec 20 2020
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Journal Of Accounting And Financial Studies ( Jafs )
The reality of quality in the SAI reports: Applied research in the Federal Board of Supreme Audit
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The research aims to shed light on the role of SAIs and the nature of their work, with the definition of the concept of quality reports and to clarify the reality of quality in the FBSA reports, the researchers reached to conclusions, including: The quality of the SAI reports is a requirement seeks to achieve any regulatory system in order to develop audit work output of the form in which its impact is reflected positively on the performance of the entities controlled, and researchers gave a set of recommendations, including: the need to increase community awareness of the importance of the FBSA Supervisory reports through conferences, seminars and workshops and that FBSA to follow-up reports, and check the quality continuously to the fa

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Wed Jan 23 2019
Journal Name
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The role of accountability measures in enhancing the results of the federal budget in government spending units
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Publication Date
Mon Sep 28 2015
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The effect of toxoplasmosis on the level of some sex hormones in males blood donors in Baghdad
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Toxoplasma gondii is a unique intracellular parasite, which infect a large proportion of the world population, but uncommonly causes clinically significant disease. The present study was performed to estimate the prevalence of toxoplasmosis in 400 apparently healthy blood donor males, their ages were between 18 and 57 years using enzyme linked immunosorbent assay, and to examine the effects of infection on total testosterone, free testosterone and follicle stimulating hormone (FSH) levels in their sera. Seroprevalence showed 10 (2.5 %) and 121 (30 %) of them had IgM and IgG antibodies respectively. Both acute and chronic toxoplasmosis in males recorded higher significant (P < 0.05) mean concentration for total and free testosterone hormone,

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Scopus (34)
Scopus
Publication Date
Thu Sep 01 2016
Journal Name
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Demulsification of Remaining Waste (Water In Oil Emulsions) After Removal Of Phenol In Emulsion Liquid Membrane Process
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Publication Date
Tue Jul 01 2014
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
VARIATIONS OF WOOD ELEMENTS IN MAIN STEM OF ALBIZIA LEBBECK (L.) BENTH. GROWING IN BAGHDAD CITY, IRAQ
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    As Albizia lebbeck is one of the important species in Iraq and the region, its wood has subjected to investigation through the assessment of differences in its element dimensions and specific gravity under Baghdad conditions. Variations of fiber length, fiber width, cell wall thickness, vessel diameter, and density of wood were examined along the stem and horizontally.  Results showed that fiber lengths were within the normal range, but their widths were narrower than common range of hardwoods. There were little increase in fiber length, width, wall thickness as the height position increased. Vessel diameter has been affected contrarily. No significant effects of  height on specific gravity could be

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Publication Date
Mon Feb 25 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Using Classification of Brown risks in Evaluation of the internal control system: Application Research in Karbala University
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Crossref
Publication Date
Fri Nov 02 2018
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Impact of Maternal Risk Factors on Birth Weight of Newborn in Two Maternity Hospitals in Baghdad City
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Objectives: A cross sectional analytic study was carried out to identify the maternal risk factors which
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Publication Date
Fri Jan 01 2021
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The effect of marketing vigilance in attracting deposits: Applied research in a sample of private commercial bank
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The aim of the research is to demonstrate the impact of the dimensions of the marketing vigilance represented by (environmental scanning, diagnostic capacity, validity and decision-making) and to attract deposits represented by (customer relationship management strategy, distribution strategy (location), promotion strategy), as the research was applied in each of Banks (Assyria International, Iraqi Middle East Investment, Business Bay, Iraqi Investment, Babel, Al Mansour Investment), and the questionnaire was adopted as a main tool for collecting data and information from a sample of (110) who are in the position (department manager, department manager, assistant Section Director, Division Officer, Unit Officer), and the statistical prog

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Publication Date
Thu Feb 28 2019
Journal Name
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Possible Options in Managing the Exchange Rate of the Iraqi Currency in light of Current Economic Conditions
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Crossref
Publication Date
Thu Nov 01 2018
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The role of tourism in economic growth-outlook for the role of tourism in Iraqi marshes development.
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The tourism activity is one of the pillars on which the economy of any country is based , the importance of the tourism sector is reflected in its potential to become an effective development alternative in many countries, especially Iraq ,this has a direct impact on the national economy as an important source in attracting hard currency and eliminating unemployment. Adding the Iraqi Marshlands to the list of effects makes it contribute to diversification of sources of income and stimulating rest of the economic sectors, the potentials and qualifications possessed by Iraq in the field of tourism and monuments have a significant impact on the state budget if they were exploited optimally. The research aims at identifying the contr

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