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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 Jan 15 2012
Journal Name
Talanta
Molecularly imprinted polymer as sorbent in micro-solid phase extraction of ochratoxin A in coffee, grape juice and urine
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A simple, environmental friendly and selective sample preparation technique employing porous membrane protected micro-solid phase extraction (μ-SPE) loaded with molecularly imprinted polymer (MIP) for the determination of ochratoxin A (OTA) is described. After the extraction, the analyte was desorbed using ultrasonication and was analyzed using high performance liquid chromatography. Under the optimized conditions, the detection limits of OTA for coffee, grape juice and urine were 0.06 ng g−1, 0.02 and 0.02 ng mL−1, respectively while the quantification limits were 0.19 ng g−1, 0.06 and 0.08 ng mL−1, respectively. The recoveries of OTA from coffee spiked at 1, 25 and 50 ng g−1, grape juice and urine samples at 1, 25 and 50 ng mL

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Publication Date
Wed Mar 30 2022
Journal Name
Modern Sport
Effect of constant str ect of constant stretching ex etching exercises in impr cises in improving the elasticity ving the elasticity of cervical v vical vertebrae for patients with cer ae for patients with cervical spondylitis’ vical spondylitis’s for ages (40-50) years
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Practicing physical activity is a very necessary requirement for all segments of society. . Many individuals, regardless of environment, age and gender, are exposed to joint diseases and injuries and pain in the neck for many and varied reasons. Treatment methods and techniques vary according to the severity of the injury, as therapeutic exercises, including stretching exercises, specifically fixed ones, are one of the ways to eliminate cases of muscle and joint dysfunction. Many individuals, regardless of environment, age and gender, are exposed to joint diseases and injuries and pain in the neck for many and varied reasons. Treatment methods and techniques differ according to the severity of the injury, as therapeutic exercises, including

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Publication Date
Thu Sep 15 2022
Journal Name
Journal Of Baghdad College Of Dentistry
The push out bond strength of bioceramic seal-er(Total Fill) after warm and cold obturation tech-niques An in vitro comparative
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Background: The goal of a root canal treatment is three dimensional obturation with a complete seal of the root canal system. The aim of this study was to evaluate and compare the effect of two warm obturation techniques, warm vertical compaction (WVC) and, carrier based obturation technique Gutta Core (GC), versus two cold obturation techniques, cold lateral compaction (CLC) and, single cone (SC) on push-out bond strength of bioceramic sealer (Total Fill) at three different root levels. Materials and Methods: Forty extracted maxillary first molars teeth with a straight round palatal root canal and mature apices were selected for this study. After sectioning the palatal roots to 11 mm from the root apex, the canals were prepared wit

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Publication Date
Thu Sep 15 2022
Journal Name
Journal Of Baghdad College Of Dentistry
The push out bond strength of bioceramic seal-er(Total Fill) after warm and cold obturation tech-niques An in vitro comparative
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Background: The goal of a root canal treatment is three dimensional obturation with a complete seal of the root canal system. The aim of this study was to evaluate and compare the effect of two warm obturation techniques, warm vertical compaction (WVC) and, carrier based obturation technique Gutta Core (GC), versus two cold obturation techniques, cold lateral compaction (CLC) and, single cone (SC) on push-out bond strength of bioceramic sealer (Total Fill) at three different root levels. Materials and Methods: Forty extracted maxillary first molars teeth with a straight round palatal root canal and mature apices were selected for this study. After sectioning the palatal roots to 11 mm from the root apex, the canals were

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Publication Date
Tue Jan 09 2018
Journal Name
Iraqi Journal Of Cancer And Medical Genetics
Photodynamic Action of low power He-Ne laser on photosensitized human Hep-2 and AMN3 cell lines with Hematoporphyrin derivative in vitro
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Photodynamic Action (PDA) by using appropriate wavelength of irradiation conjugated with porphyrin derivatives is a powerful mechanism of tumor destruction. Hematoporphyrin derivative has been shown to selectively localize in neoplastic cells and then cause destruction of them by generation of singlet oxygen when activated by low power He-Ne laser. Light which used in this study has been emitting from this laser has a wavelength equal to 632.8 nm (red light). Doses of laser had been varied from 3.6 J/cm2 to 14.4 J/cm2 . The beam of laser adjusted with a modified tissue culture plate. Cell lines had exposed to Hematoporphyrin D (HpD) for 24 hours before Laser exposure, their concentrations were varied from 5 µg/ml to 80 µg/ml. Resu

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Publication Date
Thu Feb 07 2019
Journal Name
Iraqi Journal Of Laser
Antibacterial Photodynamic Effect of 532 nm Diode-Pumped Solid State and 650 nm Diode Lasers on Methicillin Resistant Staphylococcus Aureus in Vitro
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The photodynamic inactivation against Methicillin-resistant Staphylococcus aureus using two different lasers, 532 nm diode pumped solid state laser (DPSS) in combination with safranin O and 650 nm diode laser in combination with methylene blue was investigated in the present work. A hundred swab samples were collected from patients with burn and wound infections admitted to two hospitals in Baghdad (Specialized Burns Hospital in Medical City and Al Imamein Al Jwadein Medical City Hospital) from December 2015 to February 2016 Antimicrobial susceptibility was performed by using Kirby- Bauer method. The irradiation experiments included four groups; a control group, a photosensitizer only group, a laser irradiation only group and a laser irr

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Publication Date
Fri Dec 20 2024
Journal Name
Journal Of Diabetes &amp; Metabolic Disorders
Clinical relevance of midkine as a biomarker predicting atherosclerotic risk factors in individuals with type-2 diabetes mellitus: a cross-sectional study
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Publication Date
Thu Dec 31 2015
Journal Name
مجلة كلية العلوم الاسلامية
The Secret of Marriage in Christianity A Descriptive Study
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Marriage is a holly secret in Christian religion .So it id natural that its ceremonies acquired religious form .In general the marriage is contracted by minister of religion in presence of the two parties or by a proxy or presence of parents if it is necessary . And to make the condition of publicity for the marriage ,its procedures must be made before witnesses .Also the minister of religionhave to confirm the agreement of the two parties before beginning the procedures.The marriage ceremonies are made.These procedures are religious traditions that includes praying and make blessings and putting the rings in fingers by thepriest . The marriage is a holly secret performed by the crown pray according to the church religious traditions

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Publication Date
Fri Jan 01 2016
Journal Name
Al-ustath Journal For Human And Social Sciences
Infinitive Clauses as Matrix Verbs Complementationi in Shakespeare
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The aim of this research is to find out why some matrix verbs are no longer complemented by the two types of infinitive clauses as it is the case in Elizabethan English . At that time (when Shakespeare was writing ), the same matrix verb triggers the two types of infinitive clauses as its complex transitive complementation .Such free variation is not possible in Present –Day English . In this corpus – based study , it is shown that the choice of the form of the infinitive clause is not free; there are certain syntactic ,sem- antic constraints that dete, - infinitive.

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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Heat Shock Protein70 as Biomarker in Bladder Cancer
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The present study aimed to shed light on the urine HSP70 concentration of patients with urinary bladder carcinoma UBC and control subjects as new urinary biomarker. The second aim was to associate this protein concentration with UBC stage and grade in patients with UBC. A direct ELISA was used to quantify urine HSP concentrations in 58 patients with urinary bladder carcinoma UBC with different grades (G) and stages (T) all malignant of them was transitional cell carcinoma (TCC) type , 15 from patients with urinary Bladder disorders other than cancer UBD and 15 healthy subjects(control) . Urine concentrations of HSP70 were elevated in patients with UBC compared to those without UBC (healthy and UBD, P< 0.5). There was a high signifi

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