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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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Experiment was conducted in Baghdad, three factor were used in this research included Two types of Plows included moldboard and disk plows which represented the main plot, Three forward speeds of the tillage was the second factor included 1.85, 3.75 and 5.62 km / h which represented sup plot , and Three levels of Soil Moisture was third factor included 21, 18 and 14 % in all of Vertical and Lateral Plowing Deviation, Practical and specific productivity, actual time for plowing one donam and appearance (goodness) of Tillage represented by the number of clods > 10 cm in silt clay loam soil with depth 22 cm were studied. the experiment was used Split – split plot design under randomized complete block design with three replications and Le

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Sun Jan 27 2019
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The role of accounting standards, audit and finances in control On agricultural activity to achieve sustainable development
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The agricultural activity has a great significance in the all four dimensions of sustainable development. Firstly, the economic dimension which it contributes with the GDP, as well as, it is considered as an important source to attract the investment. Secondly, the environmental dimension which also contributes with conserving of the biodiversity, combating the desertification, and increasing the farmlands. Thirdly, for its role in the social dimension to achieve the food security, to eradicate the poverty, and providing jobs. Fourthly, toward the institutional dimension as well it is considered as a source that allows all people to participate effectively, and to exchange of the local and universal experiences and perspectives. For conf

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Fri Jan 01 2021
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Mutual Derivatization in the Determination of Dapsone and Thymol Using Cloud Point Extraction Followed by Spectrophotometric Detection
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Publication Date
Sun Jan 01 2017
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Solidification Enhancement in Triplex-Tube Latent Thermal Energy Storage System Using a Combination of Nanoparticles and Fins
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Viral Load of HBV and HCV Correlation to Torque Teno Virus (TTV) Co-Infection in Iraqi Patients
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Abstract<sec> <title>Background:

While hepatitis viruses A–E are established, emerging evidence points to additional, novel viral hepatitis agents. The torqueteno virus (TTV) has garnered interest due to its prevalence among patients with hepatitis, suggesting potential hepatotropism.

Aim:

This study was conducted to detect TTV antigens in individuals infected with chronic hepatitis B (HBV) and/or C (HCV) using molecular diagnostics and to explore any associations between TTV presence and demographic characteristics of the cohort.

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Publication Date
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Exploring the Role of Hunting Cooperation, and Fear in a Prey-Predator Model with Two Age Stages
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Chronic lymphocytic leukaemia (CLL) patients display a highly variable clinical course, with progressive acquisition of drug resistance. We sought to identify aberrant epigenetic traits that are enriched following exposure to treatment that could impact patient response to therapy.

Methods

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