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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 Sep 01 2023
Journal Name
Al-khwarizmi Engineering Journal
Removal of Ciprofloxacin Antibiotic from Synthesized Aqueous Solution Using Three Different Metals Nanoparticles Synthesized Through the Green Method
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This study investigates the possibility of removing ciprofloxacin (CIP) using three types of adsorbent based on green-prepared iron nanoparticles (Fe.NPs), copper nanoparticles (Cu. NPS), and silver nanoparticles (Ag. NPS) from synthesized aqueous solution. They were characterized using different analysis methods. According to the characterization findings, each prepared NPs has the shape of a sphere and with ranges in sizes from of 85, 47, and 32 nanometers and a surface area of 2.1913, 1.6562, and 1.2387 m2/g for Fe.NPs, Cu.NPs and Ag.NPs, respectively. The effects of various parameters such as pH, initial CIP concentration, temperature, NPs dosage, and time on CIP removal were investigated through batch experiments. The res

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Publication Date
Sun Dec 29 2019
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
The static aging effect on the seedless synthesis of different ranges FAU-type zeolite Y at various factors
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This work investigates generating of pure phase Faujasite-type zeolite Y at the ranges chosen for this study via a static aging step in the absence of seeds synthesis. Nano-sized crystals may result when LUDOX AS-40 is used as a silica source for gel composition of range 6 and the crystallization step may be conducted for a period of 4 to 19 hr at 100 ⁰C. Moreover, large-crystals with high crystallinity pure phase Y zeolite can be obtained at hereinabove conditions but when hydrous sodium metasilicate is used as a silica source. The other selected ranges also offer pure phase Y zeolite at the same controlled conditions.

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Publication Date
Fri Jan 01 2016
Journal Name
Journal Of The College Of Languages (jcl)
Das Drama ( Minna von Barnhelm) von Lessing Eine analytische Studie Vorgelegt von The play of Minna von Barnhelm
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Zusammenfassung: Das Drama " Minna von Barnhelm von Lessing ist ein weltbekannts Drama, das in verschiedene Sprachen übersetzt wurde. Es beschreibt die Schwierigkeiten eines Offiziers, der bestraft wurde. Er verlor seinen Job und auch seine Ehre. Minna ist seine Verlobte, die ihn suchte und auch neben ihm stehen wollte. Trotzdem sie ihm in einem Hotel zufällig begegnete, hatten die beide immer noch Probleme. Am Ende des Dramas könnten sie alle ihrer Probleme lösen und hatten schönes Ende.

 

Abstract:
Mina von Barnhelm is a German play written by the author ( Lessing ) , it's a well-known comedy play that was translated into many languages including Arabic language .
This play is about a

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Publication Date
Fri Jan 25 2019
Journal Name
Journal Of Al-qadisiyah For Computer Science And Mathematics Vol
Predicate the Ability of Extracorporeal Shock Wave Lithotripsy (ESWL) to treat the Kidney Stones by used Combined Classifier
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Extracorporeal Shock Wave Lithotripsy (ESWL) is the most commonplace remedy for kidney stone. Shock waves from outside the body frame are centered at a kidney stone inflicting the stone to fragment. The success of the (ESWL) treatment is based on some variables such as age, sex, stone quantity stone period and so on. Thus, the prediction the success of remedy by this method is so important for professionals to make a decision to continue using (ESWL) or tousing another remedy technique. In this study, a prediction system for (ESWL) treatment by used three techniques of mixing classifiers, which is Product Rule (PR), Neural Network (NN) and the proposed classifier called Nested Combined Classi

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Publication Date
Tue Jan 31 2017
Journal Name
Journal Of Engineering
Studying the Adsorption of Lead from aqueous Solution using Local Adsorbent Material Produced from Waste Tires by Pyrolysis
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In this research a local adsorbent was prepared from waste tires using two-step pyrolysis method. In the carbonization process, nitrogen gas flow rate was 0.2L/min at carbonization temperature of 500ºC for 1h. The char products were then preceded to the activation process at 850°C under carbon dioxide (CO2) activation flow rate of 0.6L/min for 3h. The activation method produced local adsorbent material with a surface area and total pore volume as high as 118.59m2 /g and 0.1467cm3/g, respectively. The produced . local adsorbent (activated carbon) was used for adsorption of lead from aqueous solution. The continuous fixed bed column experiments were conducted. The adsorption capacity performance of prepared activated carbons in this work

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Publication Date
Tue Jan 01 2019
Journal Name
Research Journal Of Pharmacy And Technology
New Mode Semi-Automated Turbidimetric Determination of Mefenamic Acid by Ayah 6SX1-ST-2D Solar cell-CFI Analyser
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Publication Date
Sun Mar 28 2021
Journal Name
Journal Of The College Of Education For Women
A Critical Discourse Analysis of Martin Crimp’s Piece “Advice to Iraqi Women”: عفراء عبد الحسين ناصر , سراب خليل
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Language is a vehicle for social values and ideologies that a man intends or attempts to express. Dramatic texts are one of the discursive practices that embody values and ideologies. What is expressed in dramatic text is deliberate because it is meant to affect other’s values, trends and ideologies in one way or another. Such ideologies and values are not explicit. To bring them out requires putting language under scrutiny to unveil what is implied. The present study attempts to analyze a dramatic script entitled Advice to Iraqi Women by the British playwright Martin Crimp in an attempt to unveil the intended political ideologies underlying the text. The title reflects a political aspect embedded in the word “Iraqi” that

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Publication Date
Fri Feb 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
A Comparison of Parameters Estimation Methods for the Negative Binomial Regression Model under Multicollinearity Problem by Using Simulation
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This study discussed a biased estimator of the Negative Binomial Regression model known as (Liu Estimator), This estimate was used to reduce variance and overcome the problem Multicollinearity between explanatory variables, Some estimates were used such as Ridge Regression and Maximum Likelihood Estimators, This research aims at the theoretical comparisons between the new estimator (Liu Estimator) and the estimators

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Publication Date
Wed Jan 01 2020
Journal Name
Journal Of Clinical And Experimental Dentistry
Resistance of bonded premolars to four artificial ageing models post enamel conditioning with a novel calcium-phosphate paste
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Background: This in vitro study compares a novel calcium-phosphate etchant paste to conventional 37% phosphoric acid gel for bonding metal and ceramic brackets by evaluating the shear bond strength, remnant adhesive and enamel damage following water storage, acid challenge and fatigue loading. Material and Methods: Metal and ceramic brackets were bonded to 240 extracted human premolars using two enamel conditioning protocols: conventional 37% phosphoric acid (PA) gel (control), and an acidic calcium-phosphate (CaP) paste. The CaP paste was prepared from β-tricalcium phosphate and monocalcium phosphate monohydrate powders mixed with 37% phosphoric acid solution, and the resulting phase was confirmed using FTIR. The bonded premolars were exp

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Publication Date
Thu Feb 29 2024
Journal Name
Iraqi Journal Of Science
Finding the Exact Solution of Kepler’s Equation for an Elliptical Satellite Orbit Using the First Kind Bessel Function
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     In this study, the first kind Bessel function was used to solve Kepler equation for an elliptical orbiting satellite. It is a classical method that gives a direct solution for calculation of the eccentric anomaly. It was solved for one period from (M=0-360)° with an eccentricity of (e=0-1) and the number of terms from (N=1-10). Also, the error in the representation of the first kind Bessel function was calculated. The results indicated that for eccentricity of (0.1-0.4) and (N = 1-10), the values of eccentric anomaly gave a good result as compared with the exact solution. Besides, the obtained eccentric anomaly values were unaffected by increasing the number of terms (N = 6-10) for eccentricities (0.8 and 0.9). The Bessel

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