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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
Fri Dec 15 2023
Journal Name
Journal Of Baghdad College Of Dentistry
Cavity preparation model in rat maxillary first molars: A pilot study
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Objective: To conduct a standardized method for cavity preparation on the palatal surface of rat maxillary molars and to introduce a standardized method for tooth correct alignment within the specimen during the wax embedding procedure to better detect cavity position within the examined slides. Materials and methods: Six male Wistar rats, aged 4-6 weeks, were used. The maxillary molars of three animals were sectioned in the frontal plane to identify the thickness of hard tissue on the palatal surface of the first molar which was (250-300µm). The end-cutting bur (with a cutting head diameter of 0.2mm) was suitable for preparing a dentinal cavity (70-80µm) depth. Cavity preparation was then performed using the same bur on the tooth

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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Study the role of auxins and sytoknins on in vitro propagation of Spilanthes acmella (L.) Murr
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The technique of plant tissue culture has been used to In vitro micropropagation of Spilanthes acmella (L.) Murr. It is an ornamental and medicinal plant not cultivated in Iraq. Seeds were sterilized and cultuared on full strength Murashige and Skoog medium(1962)(MS). Naphthalene acetic acid (NAA), 6- furfuryl aminopurine (Kin.) growth regulators were used at the Initiation stage.The combination between IAA and Kin. was used in multiplication stage. IAA was used for rooting the shoots. Results showed that 1.5% sodium hypochlorite for 15 min was very effective for disinfecting and survival. Nodes exhibited relatively highest response as compared with apical meristems and leaflets culture. Supplying the culture medium with 1 mg/L.

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Publication Date
Mon Oct 09 2023
Journal Name
2023 Ieee 34th International Symposium On Software Reliability Engineering Workshops (issrew)
Semantics-Based, Automated Preparation of Exploratory Data Analysis for Complex Systems
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Publication Date
Mon Oct 01 2012
Journal Name
Iraqi Journal Of Physics
study Preparation and characterization ZnO nanoparticles and study of morphology at high temperature
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In context of this paper we prepare high purity powder ZnO nanostructures by chemical method at low temperature solution and study the effect off annealing at high temperature, ZnO nanoparticles have been successfully synthesized by chemical method at 0Cᵒ solution. In this method, suddenly reaction is occurred between zinc acetate solution and sodium hydroxide solution at 0Cᵒ, annealing temperature of powder product surfactant plays an important role in morphological changes. The nanostructures have been characterized by X-ray diffraction (XRD), Scanning Electron Microscope (SEM), differential scanning calorimetry(DSC) and UV-visible .analysis Effect of annealing temperatures on the morphology , structure and optical properties is di

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Publication Date
Sun Mar 26 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Preparation and Characterization of Montelukast Sodium ( SMLT ) as a Dual Sustained Release Buccal Strips
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An oral bi layer  sustained release (SR) strips of Sodium  Montelukast SMLT , which is selective  leukotriene  antagonist  , used  for  patients  suffered from mid-night asthma , were prepared successfully ,using different polymers, like guar  gum , carrageenan , and xanthan gum , by solvent casting method .

The results obtained by this study revealed  ,that best  fast  dissolving  film of  SMLT was  loaded  in carrageenan   polymer 57%  w\w (30mg.) ,  with  acceptable  physical properties, like film thickness , elastic endurance and  surface pH  .

Besides  to that , the  disintegration  t

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Publication Date
Tue May 13 2025
Journal Name
Journal Of Baghdad College Of Dentistry
An Antimicrobial Activity of Moringa Oleifera Extract in Comparison to Chlorhexidene Gluconate (In vitro study)
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Background: Oral diseases persist to be a major health problem all over the world. Various bacteria and fungi are found to be the possible pathogensresponsible for the oral diseases. Moringa oleifera it is an extraordinary nutritious vegetable tree with many different uses. These leaves have high medicinal value. In the present study, antibacterial and antifungal activities of aqueous extracts of plant Moringa oleifera in comparison to chlorohexidene gluconate and deionized water were determined. Materials and methods: The leaves of plant of Moringa oleifera were collected from College of Pharmacy; Baghdad, Iraq. Tested microorganism (bacterial and fungal) was isolated from different clinical specimens. In-vitroantimicrobial activity was pe

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Publication Date
Thu Aug 13 2020
Journal Name
Asia Pacific Journal Of Molecular Biology And Biotechnology
The anticancer molecular mechanism of Carnosol in human cervical cancer cells: An in vitro study
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Carnosol, a phenolic diterpene, is one of the effective anticancer agents naturally occurring in rosemary, sage, parsley, and oregano. The chemoresistance problem increased with the routinely used chemotherapy. Therefore, the efforts to find a substitute with safe and low cost have become crucial worldwide. The current study attempts to inspect the anticancer molecular mechanisms of Carnosol on modulating up- and down- regulation of multiple genetic carcinogenesis pathways. The cytotoxicity of Carnosol on Hela cells was evaluated by MTS assay. Flow cytometry was used to assess apoptosis and cell cycle arrest. The apoptotic morphological changes were obvious by dual apoptosis assay. The differential gene expression after treatment wi

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Publication Date
Tue May 13 2025
Journal Name
Journal Of Baghdad College Of Dentistry
An Evaluation of the Efficacy of Different Gingival Retraction Materials on the Gingival Tissue Displacement (A Comparative In Vivo Study)
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Background: An accurate adaptation of the crown to the finish line is essential to minimize cement dissolution and to preserve periodontium in fixed partial denture cases. An accurate adaptation of crown is possible only when preparation details are captured adequately in the impression and transferred to cast. For these reasons, gingival displacement is necessary to capture subgingival preparation details.The aim of the present study is to measure in vivo the horizontal displacement of the gingival sulcus obtained by using three new cordless retraction materials (Magic Foam Cord®, Racegel and Astringent Retraction Paste) in comparison to medicated retraction cord. Materials and method: Thirty-two patients requiring porcelain fused to me

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Publication Date
Tue Jun 20 2023
Journal Name
Baghdad Science Journal
Preparation, characterization, antioxidant activity of 1-(2-furoyl) thiourea derivatives and study the molecular docking of them as potent inhibitors of Urease enzyme
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In this work, we synthesized thirteen compounds of 1-(2-furoyl)thiourea derivatives 1-13 by conversion of 2-furoyl chloride to 2-furoyl isothiocyanate by reacting it with potassium thiocyanate in dry acetone in a quite short reflux time then, in the same pot, different of (primary and secondary amines) were added individually to achieve thiourea derivatives. The products were characterized spectroscopically using (FT-IR, 1H NMR and 13C NMR) techniques. Some of them were evaluated as antioxidant agents using DPPH radical scavenging method, and all were examined theoretically as enzyme inhibitors against Bacillus pasteurii urease (pdb id: 4ubp) and  by studying  molecular docking using Autodock (4.2.6) software.

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Publication Date
Fri May 01 2015
Journal Name
Journal Of Nuclear Medicine
Comparison of in vivo uptake of radioactive gold nanoparticles formulated using phytochemicals
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1267 Objectives Aim to evaluate 198Au nanoparticles (AuNP) biodistribution and uptake in a human prostate model for treatment. Many phytochemicals are known to have anti-tumor properties but have short half-lives in vivo. We hypothesized that using these phytochemicals to formulate and coat AuNP would inhibit enzyme cleavage and enhance their anti-tumor properties. Initial evaluations were performed in SCID mice bearing PC3 tumors. Methods : 198AuNP were formulated with the following gum Arabic, epigalocatechin gallate (EGCg) pomegranate extract and mangiferin extract. The resultant nanoparticles were evaluated in normal mice and in human prostate bearing SCID mice. The tumor bearing mice were injected intratumorally with 3-5 uCi of 198A

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