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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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Tue Aug 01 2023
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Iop Conference Series: Earth And Environmental Science
Effect of Light Source and Adenine Sulfate on the Multiplication and Rooting of Kalanchoe blossfeldiana in Vitro
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Abstract<p>This study was conducted in the Tissue Culture laboratory of the Horticultural Department of the Faculty of Agriculture at Karbala University to investigate the effects of a light source (Florescent, LED) and adenine sulfate (Ads) a 0, 40, 80, and 120 mg l-1 on the multiplication and rooting of <italic>Kalanchoe blossfeldiana</italic>. Results showed there are which achieved a 100% response percentage for multiplication and rooting when the addition of adenine sulfate (Ads) under LED light especially a concentration of 120 mg l-1 significantly increased the Shoot height, Shoot number, Number of leaves, Chlorophyll content and fresh, Dry weight. The results showed that they h</p> ... Show More
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Fri Dec 01 2023
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Structural and Magnetic Properties of MnxZn1-xFe2O4 Prepared via Sol-Gel Method
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      Manganese-zinc ferrite MnxZn1-xFe2O4 (MnZnF) powder was prepared using the sol-gel method. The morphological, structural, and magnetic properties of MnZnF powder were studied using X-ray diffraction (XRD), atomic force microscopy (AFM), energy dispersive X-ray (EDX), field emission-scanning electron microscopes (FE-SEM), and vibrating sample magnetometers (VSM). The XRD results showed that the MnxZn1-xFe2O4 that was formed had a trigonal crystalline structure. AFM results showed that the average diameter of Manganese-Zinc Ferrite is 55.35 nm, indicating that the sample has a nanostructure dimension. The EDX spectrum revealed the presence of transition metals (Mn, Fe, Zn, and O) in Mang

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Fri Jan 01 2021
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Structural characterization of nickel and zinc aluminate prepared by sol-gel technique
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Publication Date
Sun Mar 01 2020
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مجلة العلوم النفسية
Emotional sensitivity in children from the parents' point of view Preparation
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Publication Date
Sat Nov 04 2023
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Study the Effect of Formulation Variables on Preparation of Nisoldipine Loaded Nano Bilosomes
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Spectrophotometric Determination of Bismuth(III) with Arsenazo(III) Reagent in Water samples and Veterinary Preparation
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Publication Date
Sun Jun 21 2020
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Baghdad Science Journal
Spectrophotometer Determination of Cefixime in pure form and pharmaceutical preparation by Using Cloud point Extraction
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A Field-Based Cost-Effectiveness Study of Aflibercept and Bevacizumab in Treat-and-Extend Versus Pro Re Nata Protocols for Diabetic Macular Edema in Iraq
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Sat Jan 01 2022
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Bond Strength Survival of a Novel Calcium Phosphate‐Enriched Orthodontic Self‐Etching System after Various Ageing Protocols: An In Vitro Study
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Objective. This study aimed to evaluate the orthodontic bond strength and enamel‐preserving ability of a hydroxyapatite nanoparticles‐containingself‐etch system following exposure to various ageing methods. Materials and Methods. Hydroxyapatite nanoparticles (nHAp) were incorporated into an orthodontic self‐etch primer (SEP, Transbond™ plus) in three different concentrations (5%, 7%, and 9% wt) and tested versus the plain SEP (control) for shear bond strength (SBS), adhesive remnant index (ARI) scores, and enamel damage in range‐finding experiments using premolar teeth. The best‐performing formulation was further exposed to the following four artificial ageing metho

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Effect of Incorporating Chitosan to Resin Modified Glass Ionomer Cement on Shear Bond Strength to Dentin (An In vitro Comparative Study)
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Resin-modified glass ionomer cement tends to shrink due to polymerization of the resin component. Additionally, they are more prone to syneresis and imbibition during the setting process. This in vitro study evaluates the impact of chitosan, a biopolymer that is, both biomaterial and biocompatible, on the strength of dentin bonding and compares it with ACTIVA Bio-ACTIVE Restorative. The present study was aimed to assess the impact of including chitosan into Fuji II on the shear bond strength between. the restoration material and tooth dentin,

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