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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
Sat Jun 15 2019
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of the effectiveness of using platelet rich fibrin (PRF) as a sole grafting material and membrane in augmentation of dehiscence and fenestration defects encountered during dental implant surgery
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Background: Bone regeneration in dehiscence and fenestration defect can be improved with the use of platelet rich fibrin (PRF) that provides a scaffold for new bone regeneration. This study was conducted to assess the effectiveness of PRF as a graft material and membrane in dehiscence and fenestration defects. Materials and Methods: This prospective clinical study included patients who received dental implants that demonstrated peri-implant defects which were augmented using Leukocyte- PRF (L-PRF) or Advanced-PRF (A-PRF). Twenty four weeks postoperatively the defect resolution and the density of regenerated bone were assessed by CBCT and re-entry surgery. The assessment also included measurement of primary and secondary implant stability

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Publication Date
Thu Sep 01 2005
Journal Name
Journal Of Sport Sciences
Comparison study in some kinematics variables in (100) meter butterfly swimming to first and second ranking in world swimming championship Espana 2003
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The aim of study was making comparison in some kinematics variables in (100) meter butterfly swimming to first and second ranking in championship 2003 Espana, so noticed there is no such like this study in our country in comparison study for international champions therefore not specific and scientific discovering to these advanced levels, also the researchers depend on group of kinematics variables when the comparison making and it was included (50 meter the first, 50 meter the second, the differences between the first (50) meter and the second , more over basic variables in (100) meter butterfly , after having the results and treat it statistically the researchers reaches to two conclusions which was: • Success the first rank in startin

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Publication Date
Mon Jan 01 2024
Journal Name
Journal Of Engineering
An Electronic and Web-Based Authentication, Identification, and Logging Management System
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The need for participants’ performance assessments in academia and industry has been a growing concern. It has attendance, among other metrics, is a key factor in engendering a holistic approach to decision-making. For institutions or organizations where managing people is an important yet challenging task, attendance tracking and management could be employed to improve this seemingly time-consuming process while keeping an accurate attendance record. The manual/quasi-analog approach of taking attendance in some institutions could be unreliable and inefficient, leading to inaccurate computation of attendance rates and data loss. This work, therefore, proposes a system that employs embedded technology and a biometric/ w

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Crossref
Publication Date
Fri May 12 2023
Journal Name
Bulletin Of The Chemical Society Of Ethiopia
SYNTHESIS, CHARACTERIZATION, ANTIMICROBIAL STUDIES, AND MOLECULAR DOCKING STUDIES OF TRANSITION METAL COMPLEXES FORMED FROM A BENZOTHIAZOLE-BASED AZO LIGAND
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The azo ligand obtained from the diazotization reaction of 2-aminobenzothiazole and 4- nitroaniline yielded a novel series of complexes with Co(II), Ni(II), Cu(II), and Zn(II) ions. The complexes were investigated using spectral techniques such as UV-Vis, FT-IR, 1H and 13C NMR spectroscopic analyses, LC-MS and atomic absorption spectrometry, electrical conductivity, and magnetic susceptibility. The molar ratio of the synthesized compounds was determined using the ligand exchange ratio, which revealed the metal-ligand ratios in the isolated complexes were 1:2. The synthesized complexes were tested for antimicrobial activity against S. aureus, E. coli, C. albicans, and C. tropicalis bacterial species. Additionally, their binding affinities we

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Publication Date
Sun Jun 01 2014
Journal Name
Baghdad Science Journal
Multifocus Images Fusion Based On Homogenity and Edges Measures
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Image fusion is one of the most important techniques in digital image processing, includes the development of software to make the integration of multiple sets of data for the same location; It is one of the new fields adopted in solve the problems of the digital image, and produce high-quality images contains on more information for the purposes of interpretation, classification, segmentation and compression, etc. In this research, there is a solution of problems faced by different digital images such as multi focus images through a simulation process using the camera to the work of the fuse of various digital images based on previously adopted fusion techniques such as arithmetic techniques (BT, CNT and MLT), statistical techniques (LMM,

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Publication Date
Tue Oct 04 2022
Journal Name
Ieee Access
Plain, Edge, and Texture Detection Based on Orthogonal Moment
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Image pattern classification is considered a significant step for image and video processing.Although various image pattern algorithms have been proposed so far that achieved adequate classification,achieving higher accuracy while reducing the computation time remains challenging to date. A robust imagepattern classification method is essential to obtain the desired accuracy. This method can be accuratelyclassify image blocks into plain, edge, and texture (PET) using an efficient feature extraction mechanism.Moreover, to date, most of the existing studies are focused on evaluating their methods based on specificorthogonal moments, which limits the understanding of their potential application to various DiscreteOrthogonal Moments (DOMs). The

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Publication Date
Tue Dec 01 2009
Journal Name
J. Appl. Sci
Watermarking based Fresnel transform, wavelet transform, and chaotic sequence
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Scopus
Publication Date
Thu Jan 30 2020
Journal Name
Journal Of Engineering
Design and Analysis WIMAX Network Based on Coverage Planning
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In this paper, wireless network is planned; the network is predicated on the IEEE 802.16e standardization by WIMAX. The targets of this paper are coverage maximizing, service and low operational fees. WIMAX is planning through three approaches. In approach one; the WIMAX network coverage is major for extension of cell coverage, the best sites (with Band Width (BW) of 5MHz, 20MHZ per sector and four sectors per each cell). In approach two, Interference analysis in CNIR mode. In approach three of the planning, Quality of Services (QoS) is tested and evaluated. ATDI ICS software (Interference Cancellation System) using to perform styling. it shows results in planning area covered 90.49% of the Baghdad City and used 1000 mob

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Crossref
Publication Date
Sat Oct 01 2011
Journal Name
Journal Of Engineering
AGENT BASED MONITORING FOR INVESTIGATION PROCESS AND MAINTENANCE IMPROVEMENT
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Agent technology has a widespread usage in most of computerized systems. In this paper agent technology has been applied to monitor wear test for an aluminium silicon alloy which is used in automotive parts and gears of light loads. In addition to wear test monitoring، porosity effect on
wear resistance has been investigated. To get a controlled amount of porosity, the specimens have
been made by powder metallurgy process with various pressures (100, 200 and 600) MPa. The aim of
this investigation is a proactive step to avoid the failure occurrence by the porosity.
A dry wear tests have been achieved by subjecting three reciprocated loads (1000, 1500 and 2000)g
for three periods (10, 45 and 90)min. The weight difference a

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Crossref
Publication Date
Sat Aug 27 2022
Journal Name
International Journal Of Health Sciences
Heterocyclic compounds-based liquid crystals: Synthesis and mesomorphic properties
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A series of liquid crystals comprising a heterocyclics dihydro pyrrole and 1,2,3-triazole rings [VII]-[X] were synthesized by many steps starting from a reaction of 3,3'-dimethyl-[1,1'-biphenyl]- 4,4'-diamine with chloroacetyl chloride in a mixture of solutions DMF and TEA to synthesise the compounds [I], then the compounds [I] reacted with malononitrile in 1,4-dioxane and TEA solutions to produce compounds [II], then the first step is repeated with compound [II] where it reacted with chloroacetyl chloride in mixture of DMF and TEA to give compound [III], this compound reacted with sodium azide in the presence of sodium chloride and DMF as solvent to produce the compound [IV], which reacted with acrylic acid by a 1.3 dipolar reaction in sol

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