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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 Jul 01 2024
Journal Name
Journal Of Language Teaching And Research
Emotional Blackmail in Breaking Bad Series: A Pragma-Stylistic Study
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Although language research has focused on blackmail in general, less attention has been paid to emotional blackmail. To date, researchers could not locate any literature that examines emotional blackmail from a linguistic standpoint. The current study is intended to fill this gap by scrutinizing emotional blackmail from a pragma-stylistic point of view by examining the style of the characters in selected episodes extracted from the American Breaking Bad series. To carry out the study, an eclectic model comprising kinds of emotional blackmailers by Forward and Frazier (1997), Searles’ speech acts (1979), Grice’s maxims (1975), Brown and Levinson’s politeness (1987), Culpeper’s impoliteness (1996), and Simpson’s stylistic le

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Publication Date
Thu Dec 28 2023
Journal Name
Al–bahith Al–a'alami
Digital Interactive Elements in The Twitter Platform: An Analytical Study
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The primary issue addressed in this research revolves around identifying the interactive elements provided by the Twitter platform and understanding their utilization by digital newspapers with official accounts. These newspapers broadcast content in line with their policies. This study is classified within descriptive research that employed a survey method and content analysis tool. The methodology relies on the "how was it said?" approach to categorize the analysis. The research yielded the following results:
Twitter utilized numerous interactive elements for disseminating tweets, which include "text, branching links, hashtags, digital images, digital videos, digital audio, and digital polls." However, thes

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Publication Date
Tue Jul 31 2018
Journal Name
Revue Académique De La Recherche Juridique
Jurisdiction in the Professional Football Player Contract – A Comparative Study
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Is no longer a football player looks to sport as a means of entertainment and physical development. But become see as part of The economic and is getting in return for the effort of، Through a contract with a club to organize the activity which is called a contract of professional, This contract is similar to the rest of the contracts in terms of problems and dispute that arise during the implementation or after it ends because of the nature of sports to such disputes and privacy being subject to special rules (regulations, national and international professional) required that subject to judicial bodies private mission confined settle sports disputes these entities and is affiliated unions legal committees and the court of arbitration for

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Single Dose Antibiotic Prophylaxis in Outpatient Oral Surgery Comparative Study
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         It is clear that correct application of antibiotic prophylaxis can reduce the incidence of infection  resulting from the bacterial  inoculation in a variety of clinical situations; it cannot   prevent  all  infections  any  more  than it  can   eliminate  all  established infections. Optimum  antibiotic   prophylaxis  depends on:  rational  selection  of the drug(s),  adequate  concentrations  of the  drug  in  the  tissues that  are at risk, and attention to  timing  of  administration.  Moreover,  the  risk  of

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Scopus (1)
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Publication Date
Thu Mar 12 2026
Journal Name
Al–bahith Al–a'alami
Evaluation in the Kurdish Media Institutions (A Descriptive Study Survey)
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The importance of evaluation depends on many institutions, whether governmental or private, including media institutions, rely on the list to evaluate the weight of things and appreciation, as well as judging things, achievements, and everything related to the institution is concerned. Because through evaluation, institutions can recognize weaknesses and strengths. It is also an effective tool for management review, through which the institution can review everything related to planning and decision-making, leadership, incentives and other administrative matters.

Therefore, this study attempts to shed light on the evaluation process, its basics and its importance in general and in the Kurdish media institutions as a model in part

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Crossref
Publication Date
Thu Jan 31 2019
Journal Name
Journal Of The College Of Education For Women
A prospective study on sexual deviation deployed in Baghdad crimes
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The current research aims to identify the types and rates and the reasons for the crimes that are with the origin and sexual scattered deviation between the fabric of Iraqi society, which reticent about because of the culture of the community, where he offered a researcher investigator justice and tribal leaders and lawyers about proportion and the types and causes of crime is the origin of sexual deviance and finally a question asked a researcher in 1000 young lived their adolescence days of the former regime (1979-2003) from going to brothels researcher found that 920 people and 92% had gone to the house to practice adultery and that 70 of them, and by 7% had engaged in masturbation only and that 10 of them have not committed anything

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Publication Date
Thu Dec 15 2022
Journal Name
Bionatura
Comparative morphoanatomical study for the same rodents species in Iraq
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Samples (4th) reviewed are deposited and stored in the Iraqi Natural History Museum (INHM), and there are 4th of them. Sciurus anomalous (Güldenstädt, 1785) species are preserved and mummified. It is a Caucasian squirrel (S. anomalus) that was medium in size, with a grayish-to-chestnut color, a golden gray back, and a golden tail. It is found in the forests of East and Southeast Asia. The variety possessed for the study was previously registered in the vertebrate literature by several authors and was stored by scientific methods in the museum. As a result of the multiplication and growth of these species, and to know the environmental changes that occurred in them, they were compared with models and samples found throughout Iraq

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Publication Date
Wed May 02 2012
Journal Name
Journal Of Planner And Development
the population in Iraq up to 2035 an analytical study
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The population studies are one of the difficult tasks facing the world in all periods. most of the researchers and who have relationship to population policies and development plans, may have succumbed to the idea that the population problem is based and confined mainly in the rate of increase in population, or the so – called population explosion, and not the content because of its pressure on resources and there is no problem of population if the resources are available and therefore no need for the development and implementation of population policies in any way . While the population policies here should take a range of general and comprehensive in every respect to population and demographic phenomena distribution, not only

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
A Study on Cosmetic Products Marketed in Iraq: Microbiological Aspect
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Cosmetic products contain variable amounts of nutrients that support microbial growth. Most contaminants   in   cosmetic   products   include bacteria such as Staphylococcus, Pseudomonas, Klebsiella,   Achromobacter   and   Alcaligenes. Contaminated water  is  a  likely  source  of organisms found in cosmetic products. Products such as shampoo, hand and body lotion, facial cleanser,  and liquid soaps were analyzed. In this study, out of 60 cosmetic products analyzed, 26.4% were found to be contaminated.    Most of the contamination was from bacteria and no fungal contamination was detected.  The highest level o

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Crossref
Publication Date
Tue Dec 27 2022
Journal Name
College Of Islamic Sciences
Verbal joint in the Holy Quran A descriptive analytical study
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The research paper talks about one of the topics that deals with one of the high-style styles in the Holy Qur’an that carries with it a high and influential style in directing the Qur’anic context, as the verses are singled out with certain words, each of which came out to other meanings, which is what was called in the past “what the wording agreed and the meaning differed Or the so-called “faces and analogues” and the meaning of analogues in the language and the Qur’an; To mention a word in a place and it means a meaning other than the other, and to interpret each word with a meaning other than the other meant by the faces, and accordingly the goal of the research is in the linguistic significance, in order to reveal the tr

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