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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 Sep 03 2017
Journal Name
Baghdad Science Journal
Toxicity Reduction of Reactive Red Dye-238 Using Advanced Oxidation Process by Solar Energy
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Decolorization of red azo dye (Cibacron Red FN-R) from synthetic wastewater has been investigated as a function of solar advanced oxidation process. The photocatalytic activity using ZnO as a photocatalysis has been estimated. Different parameters affected the removal efficiency, including pH of the solution, initial dye concentration and H2O2 concentration were evaluated to find out the optimum value of these parameters. The results proved that the optimal pH value was 8 and the most efficient H2O2 concentration was 100mg/L. Toxicity reduction percent for effluent solution was also monitored to assess the degradation process. This treatment method was able to strongly reduce the color and toxicity of reactive red dye-238 to about (99 an

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Publication Date
Tue Jun 30 2020
Journal Name
Pakistan Journal Of Phytopathology
PROTECTIVE EFFECT OF OLIVE POLYPHENOLS ON WATERMELON AGAINST FUSARIUM OXYSPORUM F. SP. NIVEUM INFECTION
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Publication Date
Sun Jul 24 2022
Journal Name
Healthcare
Incidence of Gingival Black Triangles following Treatment with Fixed Orthodontic Appliance: A Systematic Review
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This systematic review aimed to investigate the relation between orthodontic treatment (OT) and the incidence of the gingival black triangle (GBT) after completing treatment with a fixed orthodontic appliance, as well as the associated risk factors and the level of alveolar bone. Electronic and hand searches were conducted in three electronic databases for relevant articles published up to March 2022. Retrieved articles went through a two-step screening procedure, and the risk of bias (RoB) was assessed by the Joanna Briggs Institute checklists. The incidence of GBT after OT was set as the primary outcome, while the secondary outcomes were the risk factors associated with GBT and alveolar bone loss following OT. Out of 421 papers, 5

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Publication Date
Tue Dec 01 2020
Journal Name
Journal Of Engineering
Development of Regression Models for Predicting Pavement Condition Index from the International Roughness Index
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Flexible pavements are considered an essential element of transportation infrastructure. So, evaluations of flexible pavement performance are necessary for the proper management of transportation infrastructure. Pavement condition index (PCI) and international roughness index (IRI) are common indices applied to evaluate pavement surface conditions. However, the pavement condition surveys to calculate PCI are costly and time-consuming as compared to IRI. This article focuses on developing regression models that predict PCI from IRI. Eighty-three flexible pavement sections, with section length equal to 250 m, were selected in Al-Diwaniyah, Iraq, to develop PCI-IRI relationships. In terms of the quantity and severity of eac

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Publication Date
Wed Apr 19 2017
Journal Name
Iraqi Dental Journal
Matching the Iris Color of Ocular Prosthesis Using an Eye Contact Lens: New Technique
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Publication Date
Wed Jan 01 2014
Journal Name
Journal Of The College Of Languages (jcl)
بزووتنةوةى (روانـــــطة) قؤناغيَكى نويَي شيعرى كوردى Rwanga Movement: a New Stage of Kurdish Poetry
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Rwanga (view) movement is a new Kurdish poetry movement. Some poets and modern storywriters published a manifest in 1970. They have made a group of changes in the content and appearance of Kurdish poetry. They were under the influence of western literature schools such as Surrealism, Dadaism and Existentialism. Likewise, the impact of the new Arabic literature that appeared by the end of 1960s on them was obvious as they were imitating such literatures. Nevertheless, the condition of Kurdistan at that time was in need of a new literature to express that new stage. Sherko Bekas was one of those poets who became the dynamo of the poetic movement in which the rebellion spirit was embodied in the modern way of dealing with culture, rhyme, rh

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Publication Date
Sun Mar 30 2003
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Improvement of CIATIM-201 Grease Properties for Use under Severe Conditions using Suitable Additives
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Publication Date
Fri Sep 01 2017
Journal Name
Journal Of Engineering
Fire Flame Influence on the Behavior of reinforced Concrete Beams Affected by Repeated Load
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The influence and hazard of fire flame are one of the most important parameters that affecting the durability and strength of structural members. This research studied the influence of fire flame on the behavior of reinforced concrete beams affected by repeated load. Nine self- compacted reinforced concrete beams were castellated, all have the same geometric layout (0.15x0.15x1.00) m, reinforcement details and compressive strength (50 Mpa). To estimate the effect of fire flame disaster, four temperatures were adopted (200, 300, 400 and 500) oC and two method of cooling were used (graduated and sudden). In the first cooling method, graduated, the tested beams were leaved to cool in air while in the second method, sudden, water splash was use

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Publication Date
Fri May 01 2020
Journal Name
Journal Of Physics: Conference Series
The Product of Automorphic Weighted Composition Operators on Hardy Space H <sup>2</sup>
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Publication Date
Sat Apr 01 2023
Journal Name
Viii. International Scientific Congress Of Pure, Applied And Technological Sciences (minar Congress)
DETERMINING AN APPROPRIATE INITIAL VALUE OF ECCENTRICITY FOR LOW EARTH SATELLITES USING EULER METHOD
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The major goal of this research was to use the Euler method to determine the best starting value for eccentricity. Various heights were chosen for satellites that were affected by atmospheric drag. It was explained how to turn the position and velocity components into orbital elements. Also, Euler integration method was explained. The results indicated that the drag is deviated the satellite trajectory from a keplerian orbit. As a result, the Keplerian orbital elements alter throughout time. Additionally, the current analysis showed that Euler method could only be used for low Earth orbits between (100 and 500) km and very small eccentricity (e = 0.001).

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