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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
Tue Sep 08 2020
Journal Name
Baghdad Science Journal
Hiding the Type of Skin Texture in Mice based on Fuzzy Clustering Technique
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A substantial matter to confidential messages' interchange through the internet is transmission of information safely. For example, digital products' consumers and producers are keen for knowing those products are genuine and must be distinguished from worthless products. Encryption's science can be defined as the technique to embed the data in an images file, audio or videos in a style which should be met the safety requirements. Steganography is a portion of data concealment science that aiming to be reached a coveted security scale in the interchange of private not clear commercial and military data. This research offers a novel technique for steganography based on hiding data inside the clusters that resulted from fuzzy clustering. T

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Publication Date
Thu Dec 31 2015
Journal Name
مجلة كلية العلوم الاسلامية
The Secret of Marriage in Christianity A Descriptive Study
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Marriage is a holly secret in Christian religion .So it id natural that its ceremonies acquired religious form .In general the marriage is contracted by minister of religion in presence of the two parties or by a proxy or presence of parents if it is necessary . And to make the condition of publicity for the marriage ,its procedures must be made before witnesses .Also the minister of religionhave to confirm the agreement of the two parties before beginning the procedures.The marriage ceremonies are made.These procedures are religious traditions that includes praying and make blessings and putting the rings in fingers by thepriest . The marriage is a holly secret performed by the crown pray according to the church religious traditions

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Publication Date
Sun Dec 25 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis, Molecular Docking Study and Cytotoxicity Evaluation of some Quinazolinone Derivatives as Nonclassical Antifolates and Potential Cytotoxic Agents
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Abstract

A series of new 4(3H)-quinazolinone derivatives (S1-S4) were synthesized and characterized   by FTIR,1HNMR and 13CNMR .Their cytotoxic activity against a set of human cancer cell lines MCF-7 (breast) and A549 (lung) was evaluated using MTT assay. To detect their selectivity toward cancer cells, the compounds were also tested against epithelial cells derived from normal human fibroblast (NHF). Methotrexate (MTX) was used as a reference for comparison . All the tested compounds exhibited toxicity against the normal cells lower than cancer cells. All the tested compounds displayed higher cytotoxicity against lung cancer cell line (A549) than MTX with the most

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Publication Date
Sat Dec 28 2024
Journal Name
Dental Hypotheses
Assessment of Color Change of Artificial White Spot Lesions after Sandblasting with Bioactive Glass, Resin Infiltration, or Microabrasion Followed by Color Stability Test by pH Cycling: An in Vitro Study
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Introduction: This study aimed to assess the color change of human teeth with artificial enamel white spot lesions (WSLs) after sandblasting with bioactive glass, resin infiltration, and microabrasion and to test color stability after pH cycling. Methods: Fifty extracted human mandibular first molars were randomly assigned into five groups: Sound, WSLs (untreated), and WSLs sandblasted with bioactive glass (Sylc), WSLs treated by resin infiltration (ICON), and WSLs treated by microabrasion (Opalustre), respectively. All specimens underwent a pH cycling procedure. The color parameters for each specimen were assessed using an Easyshade dental spectrophotometer at different time stages then the color changes (ΔE) were calculated. Results: The

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Publication Date
Tue Mar 30 2021
Journal Name
College Of Islamic Sciences
Need and transgression in Surat (Abs) Semantic grammatical study: Need and transgression in Surat (Abs)
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      The research aims to highlight the significance and composition and the diversity of meanings and the Quranic context in the necessary and transgressive verbs in Surat (Abs).

      This research consists of : a preamble , and two studies . The researcher addressed in the preliminary the importance of the phenomenon of necessity and infringement, the signs of the necessary action , the structure and controls of the act , the methods of infringement , its sections and signs.

      As for the first topic : The researcher addressed the necessary verbs in Surat Abs , an applied study in terms of grammati

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Preparation and Evaluation of Liquid and Solid Self-Microemulsifying Drug Delivery System of Mebendazole
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The aim of present study was to develop solid and liquid  self-microemulsifying drug  delivery system of poorly water soluble drug mebendazole using Aerosil 200 as solid carrier.  Microemulsions are clear, stable, isotropic liquid mixtures of oil, water and surfactant, frequently in combination with a co-surfactant having droplet size range usually in the range of 20-250 nm. Oleic acid, tween 80 and polypropylene glycol were selected as oil, surfactant and co-surfactant respectively and for preparation of stable SMEDDS, micro emulsion region was identified by constructing pseudo ternary phase diagram containing different proportion of surfactant: co-surfactant (1:1, 2:1 and 3:1), oil and water. In brief S/ CoS mix means su

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Publication Date
Wed Oct 29 2025
Journal Name
The Indonesian Biomedical Journal
Genotype Combination of rs1042044 and rs6458093 in GLP-1R as A Genetic Risk for Osteoporosis in Postmenopausal Iraqi Women
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BACKGROUND: Many genetic factors are known to be related to osteoporosis, and currently the role of the glucagon-like peptide-1 receptor (GLP-1R) gene in bone health has been studied intensively. Some variation of this gene, such as rs1042044 and rs6458093, are known to be linked to metabolic diseases and lower bone mineral density, however their specific contribution to osteoporosis remains largely unexplored. Therefore, this study was conducted to investigate the combined genotypic effect of rs1042044 and rs6458093 as a genetic risk factor for osteoporosis in postmenopausal Iraqi women.METHODS: Blood samples from 75 osteoporosis patients and 75 healthy controls, aged 45-85, were collected. DNA was extracted, and a region of GLP-1R

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Publication Date
Sun Jan 15 2012
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Molecularly imprinted polymer as sorbent in micro-solid phase extraction of ochratoxin A in coffee, grape juice and urine
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A simple, environmental friendly and selective sample preparation technique employing porous membrane protected micro-solid phase extraction (μ-SPE) loaded with molecularly imprinted polymer (MIP) for the determination of ochratoxin A (OTA) is described. After the extraction, the analyte was desorbed using ultrasonication and was analyzed using high performance liquid chromatography. Under the optimized conditions, the detection limits of OTA for coffee, grape juice and urine were 0.06 ng g−1, 0.02 and 0.02 ng mL−1, respectively while the quantification limits were 0.19 ng g−1, 0.06 and 0.08 ng mL−1, respectively. The recoveries of OTA from coffee spiked at 1, 25 and 50 ng g−1, grape juice and urine samples at 1, 25 and 50 ng mL

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Publication Date
Wed Mar 30 2022
Journal Name
Modern Sport
Effect of constant str ect of constant stretching ex etching exercises in impr cises in improving the elasticity ving the elasticity of cervical v vical vertebrae for patients with cer ae for patients with cervical spondylitis’ vical spondylitis’s for ages (40-50) years
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Practicing physical activity is a very necessary requirement for all segments of society. . Many individuals, regardless of environment, age and gender, are exposed to joint diseases and injuries and pain in the neck for many and varied reasons. Treatment methods and techniques vary according to the severity of the injury, as therapeutic exercises, including stretching exercises, specifically fixed ones, are one of the ways to eliminate cases of muscle and joint dysfunction. Many individuals, regardless of environment, age and gender, are exposed to joint diseases and injuries and pain in the neck for many and varied reasons. Treatment methods and techniques differ according to the severity of the injury, as therapeutic exercises, including

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Publication Date
Tue Oct 13 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Immunohistochemical expression of ICAM-1 and Cortactin as cell adhesive molecule and invasive markers in Hodgkin’s and non-Hodgkin’s lymphoma of the head and neck region (A comparative study)
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Background: Lymphomas are a group of diseases caused by malignant lymphocytes that accumulate in lymph nodes and cause the characteristic clinical features of lymphadenopathy. Intercellular adhesion molecule-1 (ICAM-1) (CD54) is a transmembrane glycoprotein belonging to the immunoglobulin superfamily of adhesion molecules. Cortactin was first identified as one of the major substrates for src kinase. because it localized to Cortical actin structures, The aims of this study was to evaluate and compare the immunohistochemical of ICAM-1 expression as cell adhesion molecule marker and Cortactin expression as invasive marker. Material and Methods: This study was performed on (68) formalin-fixed, paraffin-embedded blocks, histopathologically diagn

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