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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 2021
Journal Name
E3s Web Of Conferences
Experimental Investigation of Bearing Capacity of Screw Piles and Excess Porewater Pressure in Soft Clay under Static Axial Loading
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In this study, the behavior of screw piles models with continuous helix was studied by conducting laboratory experimental tests on a single screw pile that has several aspect ratios (L/D) under the influence of static axial compression loads. The screw piles were inserted in a soft soil that has a unit weight of 18.72 kN/m3 and moisture content of 30.19%. Also, the soil has a liquid limit of 55% and a plasticity index of 32%. A physical laboratory model was designed to investigate the ultimate compression capacity of the screw pile and measure the generated porewater pressure during the loading process. The bedding soil was prepared according to the field unit weight and moisture content and the failure load was assumed correspondin

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Publication Date
Fri Feb 10 2023
Journal Name
Dentistry Journal
The Role of Social Media in Communication and Learning at the Time of COVID-19 Lockdown—An Online Survey
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This study aimed to assess orthodontic postgraduate students’ use of social media during the COVID-19 lockdown. Ninety-four postgraduate students (67 master’s students and 27 doctoral students) were enrolled in the study and asked to fill in an online questionnaire by answering questions regarding their use of social media during the COVID-19 lockdown. The frequency distributions and percentages were calculated using SPSS software. The results showed that 99% of the students used social media. The most frequently used type of social media was Facebook, 94%, followed by YouTube, 78%, and Instagram, 65%, while Twitter and Linkedin were used less, and no one used Blogger. About 63% of the students used elements of social media to l

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Publication Date
Fri Jun 16 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Effect of Molecular Imprinting on the Loading and Release of Poorly Water Soluble Drug in Hydrogel Gontact Lenses
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Therapeutic contact lenses TCLs is an approach used to enhance corneal residence time and reduce frequent instillation, which is a problem with eye drops.  The problem with CLs is loading of hydrophobic drugs. In this research the CLs were prepared with molecular imprinting MI to enhance the loading of itraconazole, which is used as antifungal drug for fungal keratitis. CLs using different  concentration of hydroxyethyl methacrylate HEMA and methacrylic acid MAA were prepared with and without MI using PEGDA (25 μL) and AIBN (37 mg) as crosslinker and initiator respectively. All the prepared CLs were clear and have good folding endurance. MICLs had significantly higher drug loading compared to conventional CLs. The release of i

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Publication Date
Wed Oct 20 2021
Journal Name
Journal Of Engineering Research
Effect of several patterns of floating stone columns on the bearing capacity and porewater pressure in saturated soft soil
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One of the common geotechnical problems is the construction on soft soil and the improvement of its geotechnical properties to meet the design requirements. A stone column is one of the well-known techniques used to improve the geotechnical properties of soft soils. Sometimes thick layers of soft soil imposed the designer to use floating stone columns for improvement of such soil; in this case, the designer will be lost the end bearing of the stone column. In this study, the effects of several patterns of floating stone columns distribution under footing on the bearing capacity of soil and the distribution of excess porewater pressure are investigated. The soft soil used in this study has a very low undrained shear strength (cu) of

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Publication Date
Tue Jan 03 2023
Journal Name
The Egyptian Journal Of Hospital Medicine
High Tumor Levels of Ki-67, VEGF and Endostatin Are Associated with Progression of Breast Cancer in Iraqi Women
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Background: Breast cancer (BC) is the most widespread cancer among women worldwide. Its incidence and mortality rates have risen in the previous three decades as a result of changes in risk factor profiles, improved cancer registry, and cancer detection. Objective: The study's goals were to establish if Ki-67 could be used as a potential marker in serum of cancer disease patients as well as their interaction with vascular endothelial growth factor (VEGF) and ES in various stages of breast cancer to assess their function in the progression of BC. Materials and Methods: The levels of Ki-67, VEGF and endostatin (ES) in serum were assessed by commercial enzyme linked immunosorbent assay (ELISA) kits in 60 women diagnosed with breast cancer

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Publication Date
Thu Dec 26 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Evaluation of Risk Management practices and their relationship to the Entrepreneur behavior of managers in insurance companies: applied research
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The objective of the research is to evaluate the risk management practices of the variables (risk management structure, risk management methods, key components of risk management) and their relation to the principled behavior of managers behavior(innovation, proactive, risk acceptance) By adopting the questionnaire as a main tool in collecting data from managers in the National and raq insurance companies of (50) officials Department manager, department administrator, unit administrator, and analyzed their answers using the SPSS In calculating arithmetic mean, standard deviation, percentage weight and simple correlation coefficient. The most prominent conclusions were:1.There is a positive trend in the sample in both companies and a high

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Publication Date
Thu Dec 01 2022
Journal Name
Baghdad Science Journal
Synthesis, Characterization, and Investigation the Inhibitory Impact of Thiosemicarbazide Derivative toward the Corrosion of Mild Steel in Acidic Media
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        In this study we focused on the determination of influence the novel synthesized thiosemicarbazide derivative "2-(2-hydroxy-3-methoxybenzylidene) hydrazinecarbothioamide" (HMHC) influenced the corrosion inhibition of mild steel (MS) in a 1.0 M hydrochloric acid acidic solution.This is in an effort to preserve the metal material by maintaining it from corrosion.The synthesized inhibitor was characterized using elemental analysis, and NMR-spectroscopy. Then the corrosion inhibition capability of (HMHC) was studied on mild steel in an acidic medium by weight loss technique within variables [temperature, inhibitor concentration, and time]. The immersion periods were [1:00, 3:00, 5:00, 10:00, 24:00, and 72:00] hours and the tem

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Publication Date
Sat Apr 01 2017
Journal Name
Diyala Journal For Pure Science
Determination of IL-35, PTH, Ferritin and Other biochemical parameters in sera of Iraqi Men with chronic kidney failure.
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Chronic kidney Failure, a progressive disease, includes both medical and biochemical features that damage kidneys and decrease their abilities to work effectively, this disease is characterized by a chronic disorders to both the innate and adaptive immune systems, generate a complex and not fully understood immune dysfunction. In the present study, (30) men suffering from chronic kidney failure with age in range (40-55) year and (30) healthy men within the same range of age were enrolled in this study. The aim of this study is to highlight the role of immunological aspect (IL-35), hormonal aspects (PTH), some functional proteins and immunological electrolytes in sera of chronic kidney failure (CKF) patients. Biochemical parameters were dete

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Publication Date
Tue Aug 02 2016
Journal Name
The Iraqi Journal Of Agricultural Sciences
AN ECONOMIC ANALISYS FOR PRICING POLICY AND POLICY OF FORIGEN TRADE OF AGRICULTURAL SECTOR IN IRAQ DURING 2003-2013
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There is no doubt that Agricultural Policy is the main responsible for the degrading in Agricultural sector in Iraq during the period 2003-2013, and that was very clear from magnitude of indicators because of little sharing of each of agricultural product in GDP because it was (9.38%) in average during the study period and the annual changing of it was negative (-5.82%), and there is increasing in deficit of trade balance in Agriculture during the study period about (4185.73) million US$, and the percentage of agricultural exports from total exports was (0.14%) in average only. The foreign trade policy in Agricultural products also cannot determine map of Revealed Comparative Advantage (RCA) of Agricultural products and crops. The study sh

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Publication Date
Fri Aug 01 2014
Journal Name
Journal Of Economics And Administrative Sciences
The phenomenon of Corruption and its impact on the growing problem of Unemployment in Iraq after a year ( 2003 ).
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        Corruption is a phenomenon that exists in all times and places, they appear in the developing countries and in developed countries, and in all political systems. And its repercussions and economic repercussions on the society in which it is rampant, and lead to the undermining of economic development and obstruction, is also working on increasing poverty and unemployment, as well as its role in the worsening of social problems, and political instability. And corruption is deviant behavior is illegal and contrary to the teachings of the religious and moral values. The emergence of this phenomenon is due to several reasons, including political, economic, social and cultura

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