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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
Sun Apr 07 2013
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Journal Of Educational And Psychological Researches
The Effect of Clare's Plan on Female Students' Achievement in the History Subject in the Institute of Teachers' Preparation
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Teaching through the system of personal learning, known as (Clare's plan) is amongst the most prominent plans which depend on self-education, as it received worldwide recognition. The plan lets the learner achieve learning by depending on himself after being familiar with the educational goals given to him, then he starts to solve the exercises and the drills accompanying the unit. After that, he checks his achievement by answering the self-evaluation tests. This method offers more opportunities for personal interaction than do the traditional systems, and individual leaning is a methodical expression aims at taking care of the learner and making him the locus of the processes of teaching and learning.

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Publication Date
Thu Sep 29 2022
Journal Name
World Journal Of Clinical Infectious Diseases
Five-year retrospective hospital-based study on epidemiological data regarding human leishmaniasis in West Kordofan state, Sudan
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Publication Date
Tue Dec 29 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Medication Safety in Patients under 18 Years Old; a Retrospective Study based on Iraqi Pharmacovigilance Center Database
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Medication safety is an important part of the comprehensive patient safety term. Medication safety is gaining more attention as the World Health Organization set the goal of decreasing medication harm by (50%) for the next 5 years when launching the third global challenge. Studying medication safety in the risk groups such as young ages, children are crucial to learn more about the effect of medicines in this risk group since they are not included in the clinical trials. Adverse drug reaction is defined as any harm resulted from the drug itself during medical process journey, while medication errors are any harm resulted from the treatment process rather than the drug or it is the result of the failure in a step of the treatment process

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Publication Date
Mon Jul 01 2019
Journal Name
Journal Of Engineering
The Characters of the Form in the Vernacular Architecture A comparative study of the form's characters of facades of individual houses and commercial buildings in the City of Baghdad after 2003–Zayoona district as a case study
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The characters of facades' form of the Iraqi building after 2003 have been changed, it has been described by many names. The problem of the research is that what are the features of the characters of the form in the façades of the buildings in Baghdad city after 2003? Are the façade of the individual houses or the commercial buildings is the heaviest in the visual weight? The research aims to answer those questions by choosing the vernacular architecture as a measurement tool. It is the informal image of the architecture, which is built by people informally and spontaneously, without official control and legislation to be organized. This is smellier to what has happened in Baghdad, after 2003 according to previous stud

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Publication Date
Sun Dec 01 2019
Journal Name
Baghdad Science Journal
Studying the Crystal Structure, Topography, and Anti-bacterial of a Novel Titania (TiO2 NPs) Prepared by a Sol-gel Manner
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In this research, titanium dioxide nanoparticles (TiO2 NPs) were prepared through the sol-gel process at an acidic medium (pH3).TiO2 nanoparticles were prepared from titanium trichloride (TiCl3) as a precursor with Ammonium hydroxide (NH4OH) with 1:3 ratio at 50 °C. The resulting gel was dried at 70 °C to obtain the Nanocrystalline powder. The powder from the drying process was treated thermally at temperatures 500 °C and 700 °C. The crystalline structure, surface morphology, and particle size were studied by using X-ray diffraction (XRD), Atomic Force Microscopy (AFM), and Scanning Electron Microscope (SEM). The results showed (anatase) phase of titanium dioxide with the average grain size

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Publication Date
Wed May 31 2017
Journal Name
Journal Of Engineering
Synthesis of Nanozeolite NaA from Pure Source Material Using Sol Gel Method
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In this work, the nano particles of Na-A zeolite were synthesized by sol –gel method. The samples were characterized by X-ray diffraction (XRD), X-ray  luorescence (XRF), Surface  area and pore volume, Atomic Force Microscope (AFM) and Fourier Transform Infrared Spectroscopy (FTIR). Results show that the nano A zeolite is with average crystal size is 74.77 nm., Si/Al ratio 1.03, BET surface area was 581.211m2/g and the pore volume for NaA was found equal to 0.355cm3/g.
 
 
 

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Publication Date
Wed Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Poly Acrylamide Gel Electrophoresis of Serum Protein, Application to Kala-azar Patients
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Publication Date
Sat Sep 01 2018
Journal Name
King's College London
A novel sol-gel silica formulation for management of methadone hydrochloride abuse
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Introduction: Methadone hydrochloride (MDN) is an effective pharmacological substitution treatment for opioids dependence, adopted in different countries as methadone maintenance treatment (MMT) programmes. However, MDN can exacerbate the addiction problem if it is abused and injected intravenously, and the frequent visits to the MMT centres can reduce patient compliance. The overall aim of this study is to develop a novel extended-release capsule of MDN using the sol-gel silica (SGS) technique that has the potential to counteract medication-tampering techniques and associated health risks and reduce the frequent visits to MMT centres. Methods: For MDN recrystallisation, a closed container method (CCM) and hot-stage method (HSM) were conduc

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Publication Date
Tue Aug 03 2021
Journal Name
Journal Of Global Trends In Pharmaceutical Sciences
A REVIEW: CEFPODOXIME PROXETIL (DOXEF. PROXETIL) DISCOVERY, PREPARATION, APPLICATIONS AND COMPARISON WITH CEFPODOXIME- CLAVULANIC ACID IN ACTIVITY
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Fri Jan 01 2021
Journal Name
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Measurable Mistakes in Architecture the Effect of Designer's Experience on the Propagation of Mistakes in Architectural Design - Residential Buildings in Al Sulaymaniyah City as a Case Study
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The importance of physical and nonphysical architectural design values made architectural designers need good experience to be experts of architectural values reasonably without neglecting any value in the design process.  The importance of such values made that ignoring any values and mistakes occurs in the design process. Simultaneously, architectural designers' different nature and the difference in their experiences are causing different understandings of the design values, thus causing architectural mistakes. The research problem appears from the randomly propagating of mistakes in contemporary architecture, which is about to become a phenomenon in Al Sulaymaniyah city. The research aims to find the main reason

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