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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
Thu Jun 01 2023
Journal Name
Baghdad Science Journal
Mesenchymal and stemness transdifferentiation via in-vitro infection of T24 cell line with Klebsiella pneumoniae
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Klebsiella pneumoniae has been found in the urinary tract of some bladder cancer patients. Bacterial presence within tumor tissue may affect the tumor-microenvironment and consequently influence cancer behavior, development, and treatment response. This study investigated mesenchymal and stemness transdifferentiation of bladder cancer cell line due to environmental stress of K. pneumoniae. Cultures of urothelial bladder cancer cell line (T24) were infected with K. pneumoniae with different multiplicity of infection (MOI) for two and four days. Transdifferentiation-associated features were morphologically assessed.

Moreover, transdifferentiation markers were estimated using Q-PCR and immunohistoc

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Publication Date
Sun Dec 09 2018
Journal Name
Baghdad Science Journal
Synthesis, Characterization of Poly Heterocyclic Compounds, and Effect on Cancer Cell (Hep-2) In vitro.
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A synthesis series of new heterocyclic derivatives (A2-A7) (pyrrole, pyridazine, oxazine and imidazol) derived from 4-acetyl-2,5-dichloro-1-(3,5-dinitrophenyl)-1H-pyrrole-3-carboxylate(A1) have been synthesised. Synthesis of compound (A2) by the reaction of starting material (A1) with hydroxyl amine hydrochloride in the presence of pyridine. Compound (A2) was reacted with hydrazine hydrate in dry benzene to give (A3) derivative. The compound )A3( deals with sodium nitrite to give diazonium salt, and the reaction diazonium salt with ethyl acetoacetate to produce compound (A4). To a mixture of compound (A4) and hydroxyl amine with sttired to yield (A5).Compound (A6) was prepared by reaction compound (A4) with thiosemicarbazide in presence

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Publication Date
Wed Aug 26 2020
Journal Name
Iraqi Journal Of Agricultural Sciences
EFFECT OF GAMMA RADIATION AND ETHYL METHANESULFONATE (EMS) ON POTATO SALT STRESS TOLERANCE IN VITRO
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An experiment was conducted in the Date Palm Research Units labs / College of Agricultural Engineering Sciences / University of Baghdad to assess the tolerance toward salinity stress in potato after two mutagens treatments in vitro. Potato cv. Arizona and Rivera nodal segments were irradiated with four dosages of gamma rays at 0, 10, 20, and 30 Gray and immersed in (EMS) with four concentrations included 0, 10, 20, and 30 mM. The survival rates after mutagenesis treatments were calculated and 449 lines were obtained. The lines were tested for salinity tolerance by growing in MS medium supplemented with four concentrations of NaCl at 0, 100, 150, and 200 mM and data were analyzed according to the CRD with 10 replicates and means were

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Publication Date
Sun Mar 02 2008
Journal Name
Baghdad Science Journal
In vitro antimicrobial activity of total sesquiterpene lactones and phenols isolated from some Iraqi plants
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The antimicrobial potency of the crude ethanolic extracts from different Iraqi plants were evaluated . Further more, total sesquiterpene lactones and phenolic compounds were isolated and their antimicrobial activity attempted. The results indicated that crude extracts have no activity except that of Callistemon lanceolatus. Also, the sesquiterpene lactones and phenolic compounds isolated from Callistemon lanceolatus were the most significant antimicrobial active constituents of the studied plants.

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Publication Date
Sat Nov 04 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences( P-issn 1683 - 3597 E-issn 2521 - 3512)
Study the Effect of Formulation Variables on Preparation of Nisoldipine Loaded Nano Bilosomes
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Nisoldipine (NSD) is a dihydropyridine class of calcium channel blockers used for hypertension treatment, it belongs to class II BCS (low solubility with high permeability), its absolute bioavailability is only 5% due to presystemic metabolism in the gut wall. It is also a substrate for a CYP3A and P-gp. Bilosomes are lipid bilayer vesicles incorporating bile salts in their walls to prevent degredation by GIT bile salts. The aim of this study is to prepare nisoldipine bilosomes as vesicular carrier and assess the effect of different formulation variables such as type of surfactant, amount of cholesterol, surfactant and sonication time on particle size, entrapment efficiency and poly dispersity index of the prepared bilos

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Publication Date
Sat Dec 31 2022
Journal Name
International Journal Of Dentistry
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 methods: initial debonding, 24 h water storage, one-month water stora

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Publication Date
Wed May 01 2024
Journal Name
Journal Of International Society Of Preventive And Community Dentistry
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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A<sc>bstract</sc> <sec> <title>Aim:

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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Publication Date
Sat Oct 01 2022
Journal Name
Digest Journal Of Nanomaterials And Biostructures
Preparation and study effect of vacuum annealing on structure and optical properties of AgCuInSe<inf>2</inf> thin film
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Publication Date
Sun Sep 01 2013
Journal Name
Baghdad Science Journal
Spectrophotometric Determination of Bismuth(III) with Arsenazo(III) Reagent in Water samples and Veterinary Preparation
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A simple , sensitive and accurate spectrophotometric method for the trace determination of bismuth (III) has been developed .This method is based on the reaction of bismuth (III) with arsenazo(III) in acid solution (pH=1.9) to form a blue water soluble complex which exhibits maximum absorption at 612nm .Beer's law is obeyed over the concentration range of 2-85 ?g bismuth (III) in a final volume of 20 mL( i.e. 0.1 – 4.25?g.mL-1) with a correlation coefficient of (0.9981) and molar absorptivity 1.9×104 L.mol-1.cm-1 . The limit of detection (LOD) and the limit of quantification (LOQ) are 0.0633 and 0.0847 ?g.mL-1 , respectively . Under optimum conditions,the stoichiometry of the reaction between bismuth (III) and arsenazo(III) r

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Publication Date
Sun Jun 21 2020
Journal Name
Baghdad Science Journal
Spectrophotometer Determination of Cefixime in pure form and pharmaceutical preparation by Using Cloud point Extraction
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Two simple methods spectrophotometric were suggested for the determination of Cefixime (CFX) in pure form and pharmaceutical preparation. The first method is based without cloud point (CPE) on diazotization of the Cefixime drug by sodium nitrite at 5Cº followed by coupling with ortho nitro phenol in basic medium to form orange colour. The product was stabilized and measured 400 nm. Beer’s law was obeyed in the concentration range of (10-160) μg∙mL-1 Sandell’s sensitivity was 0.0888μg∙cm-1, the detection limit was 0.07896μg∙mL-1, and the limit of Quantitation was 0.085389μg∙mL-1.The second method was cloud point extraction (CPE) with using  Trtion X-114 as surfactant. Beer

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