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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 Jan 08 2024
Journal Name
Al-academy
Aesthetics of experimentation In short television films
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Experimentation Multi effective and fertile grew human desire to discover new ways to express beauty in artwork .And dabble term experimentation in the performing arts and arts architecture, cinema and television in the test forms and interest in the visual effects and movements seek to establish and beauty and schools of thought in literature and art. This study aims to identify

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Publication Date
Mon Feb 19 2018
Journal Name
Al-academy
Performance of the comedian in Moliere plays
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This research aims to study the performance of comedian in the plays of writer Moliere . The problem of research is to answer the following question:      How does comedian Moliere's techniques in a number of his plays and funny acts?   The    research aims at revealing the means used by the comedian in his performance of a comedic character in the number of Moliere plays.                                                 

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Publication Date
Sun Jan 27 2019
Journal Name
Journal Of The College Of Education For Women
Examples of heritage houses in Jubba city
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The researcher tried to concentrate on the field study included many houses for the sake of documenting it by pictures and schemes with its history using the available data that had got from elderly whereas the rest of heritage will document in other research , in God willing .
The research confined on the studying of examples heritage houses which was some of them had built at the end of 19th century AD but, other of them had built on the beginning of 20th century . In spite of considering these buildings are important and as a sign to architect art of Jubba but, there is never full studying written about them in Western city .
The importance of this study lies on documenting sides of environmental and climatic progress which Iraq

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Publication Date
Mon Mar 29 2021
Journal Name
Journal Of Engineering
Behavior of Defective Cast in Place Piles
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This paper deals with testing defected model piles in the soil in order to study their behavior. In this respect, the results of model pile tests are discussed either geotechnically or structurally according to the type of failure.   Two parameters were studied in order to evaluate the general behavior of defective piles. These parameters include the defect location and the defect type for floating and end bearing pile. The results of the experimental work indicated that the critical case for floating pile is seen to be when the defect of (5%) at the first third of the pile length at which the decrease in the bearing capacity is about (21%), while the decrease in the bearing capacity is found to be (14%) and (10%), when

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Publication Date
Tue Feb 05 2019
Journal Name
Journal Of The College Of Education For Women
Untold Story in the Language of Theatre
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The language of theatre is made by a number of physical tools and moral elements. So as the actors, costumes, lightings and accessories represent the physical aspects of the show, they also represent its moral aspect too. When they transform from plastic words in the space of the visual show to become signs carrying its indications that give the meaning through the link, overlap and arrangement of its movements so as to finally look like as wording in a sentence carries the meaning and represent the language of theatre speech.
The show usually sends the recipient continuous signs that go beyond the limits of expressions that are conveyed by these tools, and that cover the largest part of the meaning. So what is kept hidden or unannoun

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Publication Date
Tue Nov 22 2016
Journal Name
Der Pharma Chemica
Evaluation of Commercial Antacid Tablets in Iraq
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Antacids are commonly used drugs which are considered inert and free of pharmacological effect by many patients and physicians. They are weak bases that neutralize the gastric acid and relief pain. These weak bases dissociate to neutralize gastric acid and form neutral salts. The ultimate goal of antacid therapy is to reduce the concentration and a total load of acid in gastric juice to a pH 4 - 5. This in vitro study was promised to study the acid neutralizing capacity (ANC) of six commonly available antacids tablets in the Iraqi market by using back titration method. The highest ANC values were for Rennie (17.131± 0.083 and 16.926± 0.052 mEq) in two different hydrochloric acid (HCl) concentrations 1N and 0.5 N, respectively. The static

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Publication Date
Sun Sep 26 2021
Journal Name
Al-khwarizmi Engineering Journal
Phytotoxicity of Salvinia molesta in Diesel Exposure
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Phytoremediation is one of the methods to remove various types of pollutants from water and soil using plants. Salvinia molesta, an aquatic plant, is chosen in this study to determine its ability to degrade diesel as the pollutant in synthetic wastewater with different diesel concentrations (0, 8,700, 17,400, and 26,100 mg/L) for 14 days. Total petroleum hydrocarbon (TPH) has been used as an indicator to represent diesel concentration variation in wastewater. Degradation of TPH was 85.1% for diesel concentration of 8,700 mg/L, compared with only 53.9% in the corresponding control without plant. While, acute toxicity on S. molesta exposed in diesel concentrations of 17,400 and 26,100 mg/L was observed and eventually had

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Publication Date
Sun Dec 12 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Acute Toxicity of Rutin in Mice
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Acute toxicity is a step to evaluate the toxicity of a substance. Rutin is one of the flavonoid compounds with a variety of pharmacological effects. The aim of the study is to calculate the lethal dose that affect fifty percent of the mice used in the experiment (LD50). Thirty Swiss albino male and 30 non-pregnant female mice have been divided equally and randomly into 5 treated groups and one control group (n=5)  Rutin has been administered with  concentrations 5, 2.5.1.25,0.625 and 0.312 g/kg administered as a single dose intraperitoneally (IP) while the control group received 1% DMSO (IP).  Animals were observed for any morbidity and mortality for 14 days. After 14 days the animal blood collected for biochemical and hem

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Publication Date
Wed Jan 30 2019
Journal Name
Journal Of The College Of Education For Women
The Implications of Social Solidarity in Islam
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That interdependence in Islam is cooperation, love and fraternity and give and take
and let him look rich to the poor, every Muslim is himself liable hungry and poor no matter
how many races and colors. That interdependence is cruel, spending for God and is the
greatest supporter of charities that deal with housing, food and medicine for the unemployed
and needy, and social solidarity the consolidation of the values of brotherhood and love,
where is the greatest support of corrupt and concerted community and causes prosperity in
societies and has a significant impact on the unity of Muslims and their club and their
collection. The Islamic regime tops major systems in entrusting the achievement claimed the
lives of

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Publication Date
Fri Sep 11 2020
Journal Name
Iop Conference Series: Materials Science And Engineering
Application of Nanotechnology in Iraqi Construction Projects
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