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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
Thu Mar 01 2018
Journal Name
International Journal Of Science And Nature
EXPERIMENTAL AND THEORETICAL STUDY OF 3-BENZYL -2- MERCAPTOQUINOIZOLINE-4(3H)-ONE (BMQ) AS AN INHIBITOR OF CARBON STEEL CORROSION IN ACIDIC MEDIA
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The inhibition of 3-Benzyl -2-mercaptoquinoizoline -4 (3H)-one (BMQ) on the corrosion of carbon steel in 0.5 M HCl studied by potentionstat polarization methods at 303–333 K. Results obtained show that BMQ act as inhibitor for carbon steel in HCl solution. The inhibition efficiency increase with increase in BMQ concentration. Activation parameters and Gibbs free energy for the adsorption process using Statistical Physics calculated and discussed. Quantum chemical calculations using DFT at the B3LYP/6-31G level of theory were used to calculate some electronic properties of the molecule to verify any correlation between the inhibitive effect and molecular structure of BMQ. The quantum calculations were proceeded to get data around correlati

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Publication Date
Sat Jun 25 2022
Journal Name
Al-mağallaẗ Al-šāmilaẗ Li-l-ḥuqūq
The Intent to Harm Others as a Form of Abuse of Rights – A Study in Light of U.S. Law
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In a world of limited space, the owners are always surrounded by others next to them, and, consequently, there is hardly any activity which the owner may exercise on his land which would not affect the other owners. If he builds a building, that building may block the sun's rays or the air from the buildings next to it and owned by other people. And if he runs a business, the lands adjacent to that business may be overburdened with the accompanying noise or traffic. If oil is prospected in a land, the neighboring lands may be deprived of oil or their owners may be exposed to toxic fumes. Hence the importance of researching the intention of harming others, as it is one of the most important forms of abuse in the use of the right (especially

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Publication Date
Wed Nov 26 2025
Journal Name
Alqalam Journal Of Medical And Applied Sciences
Dual Ligand Chelates: Preparation and Spectroscopic Characterization
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Here, we synthesized three new blended ligand complexes of chromium (III), iron (III), and lanthanum (III) ions with a Schiff base made from the condensation of [o-aminophenol and 2-hydroxyacetophenone in the presence of concentrated sulphoric acid (HL1)] as a primary ligand and o-nitroaniline (L2) as a secondary. The Schiff base and its dual ligand chelate were characterized using several spectroscopic studies, IR, 1HNMR, electronic and mass spectra, in addition to elemental analyses, molar conductivity measurements, and magnetic moments. The spectroscopic and analytical outcomes confirmed the formation of the chelates in a 1:1:1(L1: M: L2) ratio. Similarly, an octahedral structure became counseled for all chelates.

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Publication Date
Mon Jan 01 2024
Journal Name
Journal Of Research In Pharmacy
Cilnidipine Nanoparticles Oral Film: Preparation and Evaluation
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Cilnidipine is a dihydropyridine class of calcium channel blockers, it is classified as a BCS class II drug, characterized by a low oral bioavailability of 13%. Consequently, the utilization of nanoparticle preparation is anticipated to enhance its bioavailability. The objective of the research is to integrate cilnidipine nanoparticles into oral films as a means of enhancing patient adherence. The optimal polymers for producing Cilnidipine films were PVA cold and or HPMC E5 at different concentrations using a casting technique with glycerol as a plasticizer. The Nano suspension-based preparation of Cilnidipine's oral film containing the combination of polymers exhibited a significant enhancement in vitro dissolution, with a percentage excee

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Publication Date
Sat Mar 01 2014
Journal Name
International Journal For Sciences And Technology
Preparation of Carboxy Methylated mPEG-Block-(4-Dodecyl Anilide) Copolymers and Their Visco Metric and Surface Tension Properties in THF
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Preparation of Carboxy Methylated mPEG-Block-(4-Dodecyl Anilide) Copolymers and Their Visco Metric and Surface Tension Properties in THF

Publication Date
Fri Mar 01 2024
Journal Name
Baghdad Science Journal
Study the Structural Properties of Porous Silicon and their Applications as Thermal Sensors
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The photo-electrochemical etching (PECE) method has been utilized to create pSi samples on n-type silicon wafers (Si). Using the etching time 12 and 22 min while maintaining the other parameters 10 mA/cm2 current density and HF acid at 75% concentration.. The capacitance and resistance variation were studied as the temperature increased and decreased for prepared samples at frequencies 10 and 20 kHz. Using scanning electron microscopy (SEM), the bore width, depth, and porosity % were validated. The formation of porous silicon was confirmed by x-ray diffraction (XRD) patterns, the crystal size was decreased, and photoluminescence (PL) spectra revealed that the emission peaks were centered at 2q of 28.5619° and 28.7644° for et

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Publication Date
Wed Jun 15 2016
Journal Name
Iraqi National Journal Of Chemistry
Physical and Electrical Study of Different Carbone Nanomaterials as Modifying Material for SPCE
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In this work was prepared three different types of modified screen printed carbon electrode (SPCEs) with drops casted method, the used carbone nanomaterials were the MWCNT, functionalized –MWCNT (f-MWCNT) and After several experiments were made to find an appropriate ratio to make good GOT/f-MWCNT nanocomposite, and found the suspension mixture (1:1) from GOT/f-MWCNT (f-MWCNT-GOT). The electrical and physical properties were performed with cyclic voltammeter technique, and studied the maximum current response, the effective surface area, effect of the pH value and the determination of active surface area for MWCNT-SPCE , f-MWCNT-SPCE and f-MWCNT-GOT/SPCE as (0.04 cm2), (0.119 cm2) and (0.115 cm2) respectively, the surface coverage concent

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Publication Date
Fri Feb 01 2019
Journal Name
Indian Journal Of Natural Sciences
Surface Photometry and Morphology Properties of Spiral Galaxies: NGC4725, NGC4639 as Case Study
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In this study, two active galaxies (NGC4725, NGC4639) have been chosen to study their morphological and photometric properties, by using the IRAF ISOPHOTE ELLIPS task with griz-filters. Observations are obtained from the Sloan Digital Sky Survey (SDSS) which reaches now to the DATA Release (DR14). The data reduction of all images (bias and flat field) has been done by SDSS Pipeline. The surface photometric investigation was performed like the magnitude. Together with isophotal contour maps, surface brightness profiles and a bulge/disk decomposition of the images of the galaxies, although the disk position angle, ellipticity, and inclination of the galaxies have been done. Also, the color of galaxies was studied, where chromatic distribution

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Publication Date
Wed May 10 2023
Journal Name
Journal Of Planner And Development
The impact of population density in sustainable housing - An applied study in the city of Baghdad (Mahalla 817), Al-Bayaa as a model
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Population density represents an important indicator for determining the growth of the size of urban areas. Population density has a direct impact on the quality of life, and its excessive rise may lead to the deterioration of basic service facilities. The problem of the research is that the increase in the total population densities of the residential neighborhood may reflect negatively on the nature of the services provided to the residents in these shops, and thus the failure to achieve sustainability in the residential locality. The research assumes that the increase in population densities negatively affects the achievement of sustainability in the residential neighborhood.

 

      

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Publication Date
Sun Jun 01 2008
Journal Name
Baghdad Science Journal
Effect of physical form and washing of treated and untreated rice straw with sodium hydroxide upon chemical composition and in vitro digestibility
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Hydroxide upon the chemical composition and dry matter(DM) and organic matter(OM) digestibility . Rice straw was treated with 4% sodium hydroxide using 30% of DM basis moisture, and incubated at 40 ºC for 40 days., DM digestibility (DMD) was significantly affected (P<0.01) by the treatment , where DMD increased The objective of this experiment was to study the effect of physical form (long ,chopped and ground ) and washing rice straw treated with sodium from 42.32 to 45.41% , OM digestibility (OMD) and total digestible nutrient (TDN) increased(P<0.05) from 47.38 and 49.33 to 49.67 and 52.83% ,respectively. While hemicellulose content increased (P<0.05 ) from 261.71 to 268.17 gm/kg DM ,and metabolizable energy (ME) from 7.11 to 7.48 MJ/

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