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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
Wed Aug 30 2023
Journal Name
مجلة نسق
The Effectiveness of a Program Based on the Theory of the Five Minds in Developing Focused Reading and Extensive Reading Skills among Second-Year Middle School Students
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Publication Date
Mon Jan 01 2024
Journal Name
Journal Of The College Of Languages (jcl)
Individualism and the Symbolic Language of Imagination (Pablo Neruda as an Example)
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Pablo Neruda's artistic distinctiveness can be considered in two ideas or attitudes of romanticism. First, the imagination, which is the result of conduct and spirituality, and second, the individualism, which is a collection of mysterious mysteries from the texts of individuality based on philosophical sonnets. His collection of poems points out the ethereality and indescribability of life, employing the reality of life at the level of human perception in a symbolic language. In other words, Pablo Neruda recreates the meanings in poetry through the three ideas of reduction, interpretation, and analysis. "What is the essential connection between individualism and the symbolic language of Pablo Neruda's imagination and What are the reason

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Publication Date
Thu Aug 20 2020
Journal Name
Al-mustansiriyah Journal Of Science
The Importance of 2-AminoThiazole Schiff Bases as Antimicrobial and Anticancer Agents
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The pharmacophore 2-aminothiazole has an interesting role in pharmaceutical chemistry as this led to the synthesis of many types of compounds with diverse biological activity. Schiff base derivatives at the same time contribute to drug evolution importantly. In this review, the Schiff base derivatives of 2-aminothiazole formed and some of their metal complexes are being focused on, and the antimicrobial and anticancer activity of them is being illustrated.

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Publication Date
Thu Jun 25 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation and Characterization of Piroxicam as Self-Nano Emulsifying Drug Delivery System
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Piroxicam (PIR) is a nonsteroidal anti-inflammatory drug of oxicam category, used in gout, arthritis, as well as other inflammatory conditions (topically and orally). PIR is practically insoluble in water, therefore the aim is prepare and evaluate piroxicam as liquid self-nanoemulsifying drug delivery system to enhance its dispersibility and stability. The Dispersibilty and Stability study have been conducted in Oil, Surfactant and Co-surfactant for choosing the best materials to dissolve piroxicam. The pseudo ternary phase diagrams have been set at 1:1, 2:1, 3:1 as well as 4:1 ratio of surfactants and co-surfactants, also there are 4 formulations were prepared by using various concentrations of transcutol HP, cremophore EL and triacetin

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Publication Date
Wed Mar 18 2020
Journal Name
Baghdad Science Journal
Synthesis and Characterization of Gold Nanoparticles by Aluminum as a Reducing Agent
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             The synthesis of nanoparticles (GNPs) from the reduction of HAuCl4 .3H2O by aluminum metal was obtained in aqueous solution with the use of Arabic gum as a stabilizing agent. The GNPs were characterized by TEM, AFM and Zeta potential spectroscopy. The reduction process was monitored over time by measuring ultraviolet spectra at a range of λ 520-525 nm. Also the color changes from yellow to ruby red, shape and size of GNP was studied by TEM. Shape was spherical and the size of particles was (12-17.5) nm. The best results were obtained at pH 6.

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Publication Date
Thu Aug 20 2020
Journal Name
Al-mustansiriyah Journal Of Science
The Importance of 2-AminoThiazole Schiff Bases as Antimicrobial and Anticancer Agents
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The pharmacophore 2-aminothiazole has an interesting role in pharmaceutical chemistry as this led to the synthesis of many types of compounds with diverse biological activity. Schiff base derivatives at the same time contribute to drug evolution importantly. In this review, the Schiff base derivatives of 2-aminothiazole formed and some of their metal complexes are being focused on, and the antimicrobial and anticancer activity of them is being illustrated.

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Publication Date
Mon Jan 09 2017
Journal Name
Nauchform
Creolized Text as a Means of Modern Communication: Verbal and Visual Components
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The article considers a creolized text as a means of modern communication, describing its key verbal and visual components; the relationship of concepts polycode and creolized text has been shown; the universal basic image features have been called; the following kinds of creolized texts have been distinguished; it has been proved that the effective means of attracting the attention of the addressee is the use of expressive font features, which are divided into two groups: topographics (mechanisms of varying of areal syntagmatic of a text) and supragraphcs (change of typeface of font).

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Publication Date
Wed Mar 22 2017
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
STRATEGIC DECISION MAKING APPROACHES AND ITS INFLUENCE AT EFFICIENCY OF SERIVICE MARKETING: AN APPLIED STUDY IN GENERAL DIRECTORATE OF TRAFFIC.: STRATEGIC DECISION MAKING APPROACHES AND ITS INFLUENCE AT EFFICIENCY OF SERIVICE MARKETING: AN APPLIED STUDY IN GENERAL DIRECTORATE OF TRAFFIC.
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Strategic decision making is considered one of the important processes for senior management in contemporary business organizations and service organizations due to the properties of the service such as intangibility, concomitance and mortality. Decision-making has three approaches according to the opinions of most of the writers and researchers in the administrative area: an analytical approach, intuitive approach and behavioral approach. This research is trying to discover the nature of the relationship in terms of the link between the impact of each of these approaches and efficiency of marketing services by selecting an intentional sample of 58 researches from the Directorate General of Traffic, one of the Iraqi Interior Ministry ins

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Publication Date
Fri Dec 01 2023
Journal Name
Baghdad Science Journal
Numerical Investigation of Physical Parameters in Cardiac Vessels as a New Medical Support Science for Complex Blood Flow Characteristics
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This study proposes a mathematical approach and numerical experiment for a simple solution of cardiac blood flow to the heart's blood vessels. A mathematical model of human blood flow through arterial branches was studied and calculated using the Navier-Stokes partial differential equation with finite element analysis (FEA) approach. Furthermore, FEA is applied to the steady flow of two-dimensional viscous liquids through different geometries. The validity of the computational method is determined by comparing numerical experiments with the results of the analysis of different functions. Numerical analysis showed that the highest blood flow velocity of 1.22 cm/s occurred in the center of the vessel which tends to be laminar and is influe

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Publication Date
Fri Mar 12 2021
Journal Name
Medico Legal Update
Human Cytomegalovirus Infection as a Risk Factor for Type 2 Diabetes Mellitus Development in a Sample of Iraqi Patients
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Type 2 diabetes mellitus which abbreviate as T2DM is a complex endocrine and metabolic disorder arisingfrom genetic and environmental factors interaction which in turn induce various degrees of insulin functionalalteration on peripheral tissues. Globally, T2DM has develop into a public health problem. Therefore, Thestudy included (75) patients(37 female and 38 males) suffering from T2DM who visit al-kadhimiya teachinghospital with age range 20-80 years and (70) as healthy controls with age range 20-70 years. All studiedgroups were evaluated CMV IgG by ELISA,B. urea, S. Creatinine, cholesterol and triglyceride the resultsshowed that B.urea, S.creatinine and serum cholesterol showed a non-significant differences between studiedgroup,

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