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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
Sun Mar 01 2020
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Implement some basic health accreditation standards Issued by the Health Care Accreditation Council (HCAC) for auditing the Performance of Hospitals: Applied research at the Education Children Protection Hospital
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The health care provided by health institutions and all kinds suffers from many problems, and since the health services provided are related to human life, it is necessary to shed light on this activity and identify the causes of these problems. This research aims to Definition of health institutions (hospitals) Performance audit of these institutions according to the latest indicators, which are the standards of health accreditation for hospitals, specifically the basic standards issued by the Health Care Accreditation Council (HCAC) to reach the level of performance and Knowledge of Constraints that lead to in an acceptable manner consistent with the approved standards. In theoretical and practical study, a number of conclusions were r

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Publication Date
Mon Jan 13 2020
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Analyzing the net profitability of total investments using a constructed mathematical model: An applied research at Iraqi Middle East Bank for investment for the financial years 2008-2010
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The trading banks in Iraq invest their funds according to regulations imposed by the Central Bank in Iraq in different financial fields like stock exchanges, acquire stocks as assets that could be sold at any time as well as make loans and contributing in corporations establishment also magnitude foreign capital through direct contacts with foreign exchange markets.

We can summarize the problem of this paper as shortage in mathematical models that used in studying and analyzing these investments and according to this problem we used (a constructed mathematical model ) consists of three major indicators: profitability of total investment assets which is divided into three sub-indicators: owners equity risk indicator, debits risk i

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Publication Date
Wed Sep 30 2015
Journal Name
College Of Islamic Sciences
Issam al-Din al-Asfrani's footnote On the interpretation of the oval Imam Issam al-Din Ibrahim Arbashah al-Asfrani (Th 159 e)   Surah Al-Baqarah (verse 55-911)
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Issam al-Din al-Asfrani's footnote
On the interpretation of the oval
Imam
Issam al-Din Ibrahim Arbashah al-Asfrani
(Th 159 e)
  Surah Al-Baqarah (verse 55-911)

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Publication Date
Sun Mar 04 2018
Journal Name
Iraqi Journal Of Science
Assessment of ISNAG fluorimeter (Total fluorescence measurements at+ 90° & - 90° using four solar cell on each side for 100mm distance at 2mm path length) with well-known fluorescent molecules via CFIA
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Two well-known fluorescent molecules: fluorescein sodium salt (FSS) and 2,7-dichloro fluorescein (DCF) were tried to prove the efficiency, trustability and repeatability of ISNAG fluorimeter by using discrete and continuous flow injection analysis modes.A linear range of 0.002-1 mmol/L for FSS and 0.003-0.7 mmol/L was for DCF, with LOD 0.0018 mmol/L and 0.002 mmol/L for FSS and DCF respectively, were obtained for discrete mode of analysis. While the continuous mode gave a linear range of 0.002-0.7 mmol/L and 0.003-0.5 mmol/L for FSS and DCF respectively, the LOD were 0.0016mmol/L and 0.0018 mmol/L for FSS and DCF respectively. The results were compared with classical method at variable λex for both fluorescent molecules at 95

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Publication Date
Sat Jun 03 2023
Journal Name
Iraqi Journal Of Science
Effect Effect Effect Effect Effect Effect Effect of Thickness on Some Physical PropertiesThickness on Some Physical PropertiesThickness on Some Physical PropertiesThickness on Some Physical PropertiesThickness on Some Physical Properties Thickness on Some
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The effect of thickness variation on some physical properties of hematite α-Fe2O3 thin films was investigated. An Fe2O3 bulk in the form of pellet was prepared by cold pressing of Fe2O3 powder with subsequent sintering at 800 . Thin films with various thicknesses were obtained on glass substrates by pulsed laser deposition technique. The films properties were characterized by XRD, and FT-IR. The deposited iron oxide thin films showed a single hematite phase with polycrystalline rhombohedral crystal structure .The thickness of films were estimated by using spectrometer to be (185-232) nm. Using Debye Scherrerś formula, the average grain size for the samples was found to be (18-32) nm. Atomic force microscopy indicated that the films had

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Publication Date
Sun Jan 26 2020
Journal Name
Journal Of Global Pharma Technology
Synthesis, Characterization of 2-azido-4-(azido (2-azido-2-( azido carbonyl)-1,3-dioxoian-4-yl)methyl)– 5-((R-azido (hydroxyl) methyl- 1,3-dioxole-2-carbonyl azide. ethanol. hydrate (L-AZD) with Some Metal Complexes
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The reaction oisolated and characterized by elemental analysis (C,H,N) , 1H-NMR, mass spectra and Fourier transform (Ft-IR). The reaction of the (L-AZD) with: [VO(II), Cr(III), Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II)], has been investigated and was isolated as tri nuclear cluster and characterized by: Ft-IR, U. v- Visible, electrical conductivity, magnetic susceptibilities at 25 Co, atomic absorption and molar ratio. Spectroscopic evidence showed that the binding of metal ions were through azide and carbonyl moieties resulting in a six- coordinating metal ions in [Cr (III), Mn (II), Co (II) and Ni (II)]. The Vo (II), Cu (II), Zn (II), Cd (II) and Hg (II) were coordinated through azide group only forming square pyramidal

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Publication Date
Tue Dec 24 2024
Journal Name
المستودع الرقمي للاطاريح
نجاح منظمات الاعمال على وفق التوجه الريادي لتكنولوجيا المعلومات بحث ميداني لعينة من المصارف العراقية الخاصة == The Success of Business Organizations According To The Entrepreneurial Orientation For Information Technology An Field Research At Iraqi Private Banks
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المستودع الرقمي العراقي. مركز المعلومات الرقمية التابع لمكتبة العتبة العباسية المقدسة

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Publication Date
Thu Jun 01 2017
Journal Name
Journal Of The College Of Languages (jcl)
Das Mittelfeld im Deutschen und ihre Angabe im Arabischen Vorgelegt von
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Die vorliegende Forschung handelt es um die Satzfelder, besonders das Mittelfeld des Satzes im deutschen und Arabischen. Diese Forschung wurde mit der Satzdefinition, Satzglieder begonnen, damit wir diese klar werden und dann werden die Felder des Satzes gut gekannt. Der erste Abschnitt schlieβt auch den Mittelfeld des Satzes und, wie man das Feld erkennen und bestimmen kann. Die Forschung untersucht auch. Ob es in der arabischen Sprache den selben Struktur wie im Deutschen gibt, z.B Bildung des Satzes sowie Satzfelder bezügllich das Mittelfeld.

Der zweite Abschnitt handelt sich um den arabischen Teil und behandelt die Wortarten im Arabischen sowie den Satz als auch Satzarten (Nominal- Verbal- Halbsatz).

Danach befinden

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Publication Date
Tue Oct 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
الادارة بالرؤية المشتركة وانعكاساتها على التسويق الابداعي بحث استطلاعي لعينة من موظفي الشركة العامة للصناعات الكهربائية
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ان السبب الرئيسي لاختيار الموضوع كونه من الاساليب الادارية الحديثة التي تهدف الى انجاح المنظمة او الشركة المبحوثة, اذ تمثلت مشكلة البحث في ما دور الادارة بالرؤية المشتركة في تعزيز التسويق الابداعي بالشركة المبحوثة, يهدف البحث الى تسليط الضوء على مفهوم الادارة بالرؤية المشتركة وانعكاساتها على التسويق الابداعي للمنظمة ، باعتبارها منهج اداري حديث يسهم في تغيير وتجديد وتطوير واقع المنظمة المبحوثة( الشرك

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Publication Date
Tue Jul 20 2021
Journal Name
Materials Science Forum
Red Laser Irradiation Effect on the Structural Properties of MawsoniteCu&lt;sub&gt;6&lt;/sub&gt;Fe&lt;sub&gt;2&lt;/sub&gt;SnS&lt;sub&gt;8&lt;/sub&gt; [CFTS] Thin Films Deposited via Semi-Computerized Spray Pyrolysis Technique
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The existing investigation explains the consequence of irradiation of violet laser on the structure properties of MawsoniteCu6Fe2SnS8 [CFTS] thin films. The film was equipped by the utilization of semi-computerized spray pyrolysis technique (SCSPT), it is the first time that this technique is used in the preparation and irradiation using a laser. when the received films were processed by continuous red laser (700 nm) with power (>1000mW) for different laser irradiation time using different number of times a laser scan (0, 6, 9, 12, 15 and 18 times) with total irradiation time (0,30,45,60,75,90 min) respectively at room temperature.. The XRD diffraction gave polycrysta

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