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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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Sun Dec 01 2019
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Journal Of Accounting And Financial Studies ( Jafs )
Cost technique based on ABCII specifications and its effect in the Implementation of contracting contracts: Applied research in Al-Mansour general company for construction contracting
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The problem of research was to identify after the use of cost technology based on specifications in the validity of determining and measuring the costs of the implementation of contracting, by applying to al-Mansour General Construction Contracting Company as an appropriate alternative to the traditional costing system currently adopted, which is characterized by many shortcomings and weaknesses Which has been reflected in the validity and integrity of the calculations. To solve this problem, the research was based on the premise that: (The application of cost technology based on specifications will result in calculating the cost of the product according to the specification required by the customer, to meet his wishes properly and witho

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Publication Date
Mon Jul 01 2019
Journal Name
Journal Of Educational And Psychological Researches
The of Effect Instructional Design based on Kagan Structure In Generating Information Skills for First Intermediate Student’s In Mathematics
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The aim of the research is to identify the effect of instructional design according to Kagan structure among the first intermediate school student’s, and how skills could help in generating information in mathematics. In accordance with the research objectives, the researcher has followed the experimental research method by adopting an experimental design with two equivalent groups of post-test to measure skills in generating information. Accordingly, the researcher raised two main null hypotheses: there were no statistically significant differences at the level of significance (0.05) between the average scores of the experimental group who studied the material according to Kagan structure and th

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Publication Date
Mon Jul 07 2025
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Oxidation Communication
ANAPLASTIC LYMPHOMA KINASE EXPRESSION AND OTHER MARKERS AS A PROGNOSTIC BIOMARKER IN FEMALE PATIENTS WITH BREAST CANCER
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Breast cancer is among the primary causes of death among Iraqi women and is a serious worldwide health concern. ALK or anaplastic lymphoma kinase, is connected to several cancers, including breast cancer.. The goal of this research was to assess the prevalence of anaplastic lymphoma kinase (ALK) with Alkaline phosphatise (ALP) and Lactate dehydrogenase (LDH) together as diagnostic markers. The study comprised 60 patients with metastatic breast cancer and 60 healthy volunteers. The blood levels of the enzymes (ALP), (LDH), and ALK in Iraqi breast cancer patients are compared to those of healthy controls. It was shown that compared to healthy people, patients had breast cancer noticeably greater levels of ALK, ALP, and NDH .These biomarkers m

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Publication Date
Thu Dec 15 2022
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Al-academy
The dramatic act and its transformations in the Iraqi theatrical show "Black Astronomy play as a sample"
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The subject of the act and its transformations in the presentation is of great importance at the level of study, analysis and interpretation, and through that the researcher adopted the following title (The Dramatic Act and Its Transformations in the Iraqi Theatrical Show). The play of Black Astronomy was chosen as a sample for analysis, and the aim of the research came in order to achieve a special knowledge of the extent of the transformation that occurred between the dramatic structure of the act and theatrical embodiment and its multiple elements of operation in the Iraqi theatrical shows. It was limited to the show of the Iraqi theater in the year (2020) and included the theoretical framework that accommodated three sections. As for

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Fri Apr 01 2022
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MgCl2 and MgSO4 as draw agents in forward osmosis process for East Baghdad oilfield produced water treatment
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This study investigated a novel application of forward osmosis using different types of draw solutions for oilfield produced water treatment from the East Baghdad oilfield affiliated to the Midland Oil Company (Iraq). Magnesium chloride (MgCl2) and magnesium sulfate (MgSO4) were used as draw solutions in forward osmosis process to evaluate their effectiveness. Experiments were conducted in a laboratory scale forward osmosis system with cellulose triacetate hollow fiber membrane. In this work, sodium chloride solution was used as a feed solution with a concentration of 76 g/L (same concentration as the East Baghdad oilfield produced water) and the applied external pressure on the feed solution side was 2 bar. The impact of draw solution (DS)

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Publication Date
Wed Nov 20 2024
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New 4-amino-3-chloro benzoate ester derivatives as EGFR inhibitors: synthesis, in silico and biological analyses
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Functionalizing Location's Indications and Aesthetic Elements in Novel Film"(Pianist Film as an example): منير طه سلمان
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Sun Jan 01 2017
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His- Ventricle (HV) Interval And Syncope As Predictor For Pacemaker Implantation In Patients With Bifascicular Block (BFB)
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Transient drop in the heart beat or transient heart block (AVB) may be consider the main cause of syncope or presyncope inpatients with bifascicular block and syncope According to the Guidelines for cardiac pacing pacemaker consider part of treatment. Aims of our study were to evaluate whether there is role for EPS in patients BFB and to evaluate the symptoms after pacing. 42 patients were enrolled in this study, with mean age value (63.4± 12.2years), suffer from interventricular conductive defect and syncope; patients underwent EPS on admission time, and pacemaker implantation accordingly and programmed follow up for the device in the last four years. Our patients were 25 (59.5%) male and 17 (40.5%)female, all of them with syncope o

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Tue Feb 28 2023
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Design and Implementation of EEG-Based Smart Structure
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It has been shown recently that there is a need to design smart structures, such as smart houses, in order to be controlled in different ways. That will be in high demand due to its usefulness for some people who are incapable of reaching some control units that require direct interaction with human beings. In this paper, we propose and develop a new enhanced electroencephalography (EEG)-based smart structure setup that can be utilized to assist people, with or without disorders, to control devices in an easy and comfortable way. Ten people of a wide range of ages (20–65) and both genders actively participated in this research. Consequently, eight EEG channels are employed in this study to cover most of the brain’s regions, and the prot

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Fruit classification by assessing slice hardness based on RGB imaging. Case study: apple slices
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Correct grading of apple slices can help ensure quality and improve the marketability of the final product, which can impact the overall development of the apple slice industry post-harvest. The study intends to employ the convolutional neural network (CNN) architectures of ResNet-18 and DenseNet-201 and classical machine learning (ML) classifiers such as Wide Neural Networks (WNN), Naïve Bayes (NB), and two kernels of support vector machines (SVM) to classify apple slices into different hardness classes based on their RGB values. Our research data showed that the DenseNet-201 features classified by the SVM-Cubic kernel had the highest accuracy and lowest standard deviation (SD) among all the methods we tested, at 89.51 %  1.66 %. This

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