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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
Tue Feb 11 2025
Journal Name
Al-rafidain Journal Of Medical Sciences ( Issn 2789-3219 )
Enhancing the Antibacterial Activity of Ciprofloxacin Against Klebsiella pneumoniae by Inhibiting the AcrAB-TolC Efflux Pump System Using Phenylalanine-arginine β-Naphthylamide
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Background: Klebsiella pneumoniae shows varying degrees of resistance to antibiotic treatment; this resistance arises from multiple mechanisms, including the increased expression of multidrug (MDR) efflux pumps. An efflux pump inhibitor (EPI) is required to overcome this challenge and restore the effectiveness of antibiotics against the present MDR K. pneumoniae. Objective: To investigate the synergistic effect of the EPI Phenylalanine-Arginine β-Naphthylamide (PaβN) and Ciprofloxacin (CIP) on the expression of efflux pump genes AcrAB-TolC, isolated from CIP-resistant K. pneumoniae. Methods: 50 isolates of K. pneumoniae were collected from five different hospitals in Baghdad, Iraq. The minimum inhibitory concentration (MIC) values

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Publication Date
Fri May 01 2026
Journal Name
Results In Chemistry
Advanced spectrofluorimetric determination of ascorbic acid via serotonin hydrochloride quenching using a twin solar cell device with eight-angled blue radiation sources
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novel spectrofluorimetric flow injection analysis (FIA) method was developed for the selective quantification of ascorbic acid via fluorescence quenching of serotonin hydrochloride. The system employs a custom-designed photometric array comprising 16 irradiation sources arranged in a dual-axis matrix—eight aligned horizontally and eight orthogonally, enabling multi-angle excitation and enhanced spectral resolution. Fluorescence signals were captured using a twin-pair solar cell detector, offering high sensitivity and minimal optical interference. The method exhibited a linear calibration range of 0.1–30 limit of detection (LOD) of 0.025 μ μ g/mL with a correlation coefficient (r mol /L, equivalent to 4.403 * 10 4 μ 2 ) of 0.9966, a g

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Publication Date
Thu Aug 01 2019
Journal Name
International Journal Of Research - Granthaalayah
MULTIPLE MIXING RATIOS OF GAMMA RAY TRANSITIONS FROM 𝟔𝟎𝐍𝐝 𝟏𝟒𝟐− 𝟏𝟓𝟎 (𝐧, 𝐧 ˊ𝛄) 𝟔𝟎𝐍𝐝 𝟏𝟒𝟐− 𝟏𝟓𝟎 REACTION USING 𝒂𝟐- RATIO METHOD
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In the current work, the mixing ratios ( 𝛿 ) of gamma transitions were calculated from energy levels in the isotopes neodymium 60𝑁𝑎 142−150 populated in the 60Nd 142− 150 (n, n ˊγ) 60Nd 142− 150 using the 𝑎2 ratio method. We used the experimental coefficient (𝑎2 ) for two γ-transitions from the initial state itself, the statistical tensor 𝜌2(𝐽𝑖), associated with factor 𝑎2 , would be the same for the two transitions. The results obtained are in good agreement or within the experimental error with -those previously published. And existing contradictions resulting from inaccuracies in the empirical results of previous work. The current results confirm that the , 𝑎2 − method is used to calculate th

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Publication Date
Tue May 07 2024
Journal Name
Heliyon
Micro-shear bond strength of a novel resin-modified glass ionomer luting cement (eRMGIC) functionalized with organophosphorus monomer to different dental substrates
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Objectives: This study aims to assess and compare the micro-shear bond strength (μSBS) of a novel resin-modified glass-ionomer luting cement functionalized with a methacrylate co-monomer containing a phosphoric acid group, 30 wt% 2-(methacryloxy) ethyl phosphate (2-MEP), with different substrates (dentin, enamel, zirconia, and base metal alloy). This assessment is conducted in comparison with conventional resin-modified glass ionomer cement and self-adhesive resin cement. Materials and methods: In this in vitro study, ninety-six specimens were prepared and categorized into four groups: enamel (A), dentin (B), zirconia (C), and base metal alloys (D). Enamel (E) and dentin (D) specimens were obtained from 30 human maxillary first premolars e

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Publication Date
Tue Jan 01 2019
Journal Name
International Journal Of Pharmaceutical Research
New method for the evaluation of propranolol with phosphotungstic acidvialong distance chasing photometer (NAG-ADF-300-2) using continuous flow injection analysis
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A new, simple and sensitive method was used forevaluation of propranolol withphosphotungstic acidto prove the efficiency, reliability and repeatability of the long distance chasing photometer (NAG-ADF-300-2) using continuous flow injection analysis. The method is based on reaction between propranolol and phosphotungstic acid in an aqueous medium to obtain a yellow precipitate. Optimum parameters was studied to increase the sensitivity for developed method. A linear range for calibration graph was 0.007-13 mmol/L for cell A and 5-15 mmol/L for cell B, and LOD 207.4792 ng/160 µL and 1.2449 µg/160 µL respectively to cell A and cell B with correlation coefficient (r) 0.9988 for cell A, 0.9996 for cell B, RSD% was lower than 1%, (n=8) for the

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Publication Date
Mon Dec 20 2021
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
MOLECULAR CHARACTERIZATION OF ANISAKID NEMATODES HYSTEROTHYLACIUM SPECIES FROM JAPANESE THREADFIN BREAM NEMIPTERUS JAPONICUS (BLOCH, 1791) (PERCIFORMES, NEMIPERIDAE) FROM IRAQI MARINE WATER FISH
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The present study provides a new insight into valuable information on the diverse structure of the Anisakid population and discusses the limited species richness in the Nemipterus japonicus (Bloch,1791) (Perciformes, Nemiperidae). The fishing area consists of various locations in the Arabian Gulf (29°58 0 33 00 N48°28 0 20 E). A total of 315 marine fish were examined, (n=287) were infected. Larval stages (n= 763) encysted within the mesenteries peritoneum and viscera of fish organs were isolated, with a prevalence of 91.11% of infection and, the intensity was 2.65. Molecular analysis was carried out on thirty individuals who have examined the morphology and showed some appearance differences, by amplifying internal transcribed spacers

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Publication Date
Tue Sep 08 2020
Journal Name
Baghdad Science Journal
Improved throughput of Elliptic Curve Digital Signature Algorithm (ECDSA) processor implementation over Koblitz curve k-163 on Field Programmable Gate Array (FPGA)
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            The widespread use of the Internet of things (IoT) in different aspects of an individual’s life like banking, wireless intelligent devices and smartphones has led to new security and performance challenges under restricted resources. The Elliptic Curve Digital Signature Algorithm (ECDSA) is the most suitable choice for the environments due to the smaller size of the encryption key and changeable security related parameters. However, major performance metrics such as area, power, latency and throughput are still customisable and based on the design requirements of the device.

The present paper puts forward an enhancement for the throughput performance metric by p

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Publication Date
Sun Jun 01 2014
Journal Name
Journal Of Economics And Administrative Sciences
Different Methods for Estimating Location Parameter & Scale Parameter for Extreme Value Distribution
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      In this study, different methods were used for estimating location parameter  and scale parameter for extreme value distribution, such as maximum likelihood estimation (MLE) , method of moment  estimation (ME),and approximation  estimators based on percentiles which is called white method in estimation, as the extreme value distribution is one of exponential distributions. Least squares estimation (OLS) was used, weighted least squares estimation (WLS), ridge regression estimation (Rig), and adjusted ridge regression estimation (ARig) were used. Two parameters for expected value to the percentile  as estimation for distribution f

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Publication Date
Thu Jan 21 2021
Journal Name
Recent Innovations In Chemical Engineering (formerly Recent Patents On Chemical Engineering)
Soap Production Using Vacuum Reactive Distillation: Batch Model
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Introduction: Although soap industry is known from hundreds of years, the development accompanied with this industry was little. The development implied the mechanical equipment and the additive materials necessary to produce soap with the best specifications of shape, physical and chemical properties. Objectives: This research studies the use of vacuum reactive distillation VRD technique for soap production. Methods: Olein and Palmitin in the ratio of 3 to 1 were mixed in a flask with NaOH solution in stoichiometric amount under different vacuum pressures from -0.35 to -0.5 bar. Total conversion was reached by using the VRD technique. The soap produced by the VRD method was compared with soap prepared by the reaction - only method which

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Publication Date
Wed Feb 27 2019
Journal Name
Journal Of Nano Research
A Specific NH&lt;sub&gt;3&lt;/sub&gt; Gas Sensor of a Thick MWCNTs-OH Network for Detection at Room Temperature
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NH3 gas sensor was fabricated based on deposited of Functionalized Multi-Walled Carbon Nanotubes (MWCNTs-OH) suspension on filter paper substrates using suspension filtration method. The structural, morphological and optical properties of the MWCNTs film were characterized by XRD, AFM and FTIR techniques. XRD measurement confirmed that the structure of MWCNTs is not affected by the preparation method. The AFM images reflected highly ordered network in the form of a mat. The functional groups and types of bonding have appeared in the FTIR spectra. The fingerprint (C-C stretch) of MWCNTs appears in 1365 cm-1, and the backbone of CNTs observed at 1645 cm-1. A homemade sensi

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