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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 Mar 01 2024
Journal Name
Journal Of Applied Spectroscopy
Spectrophotometric Method for Determination of Cu(II) Using a New Schiff Base Ligand
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The Cu(II) was found using a quick and uncomplicated procedure that involved reacting it with a freshly synthesized ligand to create an orange complex that had an absorbance peak of 481.5 nm in an acidic solution. The best conditions for the formation of the complex were studied from the concentration of the ligand, medium, the eff ect of the addition sequence, the eff ect of temperature, and the time of complex formation. The results obtained are scatter plot extending from 0.1–9 ppm and a linear range from 0.1–7 ppm. Relative standard deviation (RSD%) for n = 8 is less than 0.5, recovery % (R%) within acceptable values, correlation coeffi cient (r) equal 0.9986, coeffi cient of determination (r2) equal to 0.9973, and percentage capita

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Publication Date
Mon Sep 30 2019
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Performance of Immobilized Chlorella Algae for Removing pb(II) Ions from Aqueous Solution
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This study aims to show the  effectiveness of immobilization of Chlorella green algae biomass in the form of bead for the removal of lead ions from synthetic polluted water  at various operational parameters such as pH (2–6), biosorbent dosage (0.5–20 g/L) and initial concentration (10–100 mg/L). More than 90 % removal efficiency was achieved. FTIR and SEM-EDX analysis of the biosorbent before and after sorption show differences in the functional groups on the adsorbent surface. Langmuir and Freundlich equilibrium isotherm, pseudo-first-order and pseudo-second-order kinetic models were applied to the experimental and results and show good conformity with Langmuir isotherm model and pseudo-second-order kinetic model with c

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Publication Date
Wed Dec 18 2019
Journal Name
Baghdad Science Journal
Synthesis, Cytotoxicity, Xanthine Oxidase Inhibition, Antioxidant of New Pyrazolo{3,4 d}Pyrimidine Derivatives
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         Allopurinol derivative were prepared by reacting the (1-chloroacetyl)-2-Hydropyrazolo{3,4-d}pyrimidine-4-oneiwith 5- methoxy- 2-aminoibenzothiazoleiunder certain conditions to obtain new compound  ( N- (2-aminoacetyl (5-methoxy) benzothiazole -2yl) (A4), Reaction of 5-(P-dimethyl amine benzene)-2-amino-1,3,4- oxadiazole in the presence of potassium carbonate anhydrous to yield new  compound (N-(2- aminoacetyl-5-(P-dimethyl amine benzene )-1,3,4-oxadiazoles-2-yl)(A30) and Azo compound (N-(5-(Azo-2-hydroxy-5-amino benzene)-1,3-Diazol-2yl)Allopurinol(A46). The structure of prepared compounds were confirmed by (FT-IR)

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Publication Date
Thu Jun 30 2011
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
CRACKING ACTIVITY OF PREPARED Y-ZEOLITE CATALYST USING CUMENE ON FLUIDIZED BED REACTOR
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The catalytic activity of faujasite type NaY catalysts prepared from local clay (kaolin) with different Si/Al ratio was studied using cumene cracking as a model for catalytic cracking process in the temperature range of 450-525° C, weight hourly space velocity (WHSV) of 5-20 h1, particle size ≤75μm and atmospheric pressure. The catalytic activity was investigated using experimental laboratory plant scale of fluidized bed reactor.
It was found that the cumene conversion increases with increasing temperature and decreasing WHSV. At 525° C and WHSV 5 h-1, the conversion was 42.36 and 35.43 mol% for catalyst with 3.54 Si/Al ratio and Catalyst with 5.75 Si/Al ratio, respectively, while at 450° C and at the same WHSV, the conversion w

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Publication Date
Mon Jan 18 2021
Journal Name
Materials Science And Engineering
Properties of engineered cementitious composite concrete (bendable concrete) produced using Portland limestone cement
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Bendable concrete, also known as Engineered Cementitious Composite (ECC) is a type of ultra-ductile cementitious composites reinforced with fibres to control the width of cracks. It has the ability to enhance concrete flexibility by withstanding strains of 3% and higher. The properties of bendable concrete mixes (compressive strength, flexural strength, and drying shrinkage) are here assessed after the incorporation of supplementary cementitious materials, silica fume, polymer fibres, and the use of ordinary Portland cement (O.P.C) and Portland limestone cement (IL). Mixes with Portland limestone cement show lower drying shrinkage and lower compressive and flexural strength than mixes with ordinary Portland cement, due to the ratio o

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Publication Date
Tue Nov 15 2022
Journal Name
Association Of Arab Universities Journal Of Engineering Sciences
A-mechanical properties of engineered cementitious composite concrete produced from Portland limestone cement
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Conventional concretes are almost unbending, and even a small amount of strain potential leaves them brittle. This lack of bendability is a major source of strain loss, and it has been the main goal behind the development of bendable concrete, often known with engineered ce ment composites, or ECC. This form of concrete has a lot more flexibility than regular concrete. Micromechanical polymer fibers are used to strengthen ECC. In most cases, ECC uses a 2% amount of thin, separated fibers. As a result, bendable concrete deforms but unlike traditional concrete, it does not crack. This study aims to include this kind of concrete, bendable concrete, which can be used to solve concrete problems. Karasta (CK) and Tasluja (CT) Portland Lime

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Publication Date
Fri Nov 01 2019
Journal Name
Journal Of Engineering
Assessment the Engineering Characteristics of the Smear Zone around PVDs Using Laboratory Tests
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Smear zone is usually formed around the prefabricated vertical drains (PVD’s) due to mandrel driving. The geotechnical properties of the soil in this zone exhibit significant changes that affect the performance of the PVD’s. The most relevant property in this respect is the coefficient of permeability. So far, no serious attention is paid to investigate the effects of shearing under large shear strains on the geotechnical properties of the soft soil in Fao region. In this study, an extensive laboratory testing program was conducted to assess the characteristics of the smear zone with an emphasis on the permeability coefficient of Fao soft soil. The results show that the permeability of the smear zone is about 70% of

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Publication Date
Thu May 31 2012
Journal Name
Al-khwarizmi Engineering Journal
Extraction of Penicillin V from Simulated Fermentation Broth by Liquid-Liquid Membrane Technique
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Liquid-liquid membrane extraction technique, pertraction, using three types of solvents (methyl isobutyl ketone, n-butyl acetate, and n-amyl acetate) was used for recovery of penicillin V from simulated fermentation broth under various operating conditions of pH value (4-6) for feed and (6-8) for receiver phase, time (0-40 min), and agitation speed (300-500 rpm) in a batch laboratory unit system. The optimum conditions for extraction were at pH of 4 for feed, and 8 for receiver phase, rotation speed of 500 rpm, time of 40 min, and solvent of MIBK as membrane, where more than 98% of penicillin was extracted. 

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Publication Date
Thu Sep 06 2018
Journal Name
Al-khwarizmi Engineering Journal
Performance Augmenting of a Vertical Axis Wind Turbine using Adaptable Convergent Ducting System
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Developments are carried out to enhance the performance of vertical axis wind turbines (VAWT). This paper studies the performance of the ducted wind turbine with convergent duct (DAWT). Basically, the duct technique is utilized to provide the desired wind velocity facing the turbine. Methodology was developed to estimate the decisive performance parameter and to present the effect of the convergent duct with different inlet angles. The ducted wind turbine was analyzed and simulated using MATLAB software and numerically using ANSYS-Fluent 17.2. Result of both approaches were presented and showed good closeness for the two cases of covering angles 12  and 20 respectively. Results also showed that the convergent duct with an inlet angl

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Publication Date
Sun Dec 30 2018
Journal Name
Journal Of Engineering
Abrasive Wear Characteristics of Composite Material (AA 7075 / SiC) Synthesized by Stir Casting
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Aluminum Metal Matrix Composites (ALMMCs) was prepared by using stir casting technique for AA 7075 aluminum alloy as a matrix reinforced with SiC particles at various percentages (3, 6, 9 and 12 wt. % ) and 75µm in grain size. The prepared composite material can be used for many applications such as aerospace, automobiles and many industrial sectors. Abrasive wear test was carried out by two stages: the first stage was done by changing the emery papers at various grit sizes 180, 320, 500, and 1000µm with constant applied load 15N. While the second stage was carried out by changing the applied loads 5, 10, 15, 20 and 25N with constant emery paper at 320 µm grit size. Microstructure examination, hardness test and roughn

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