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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 Jul 21 2023
Journal Name
Journal Of Engineering
SIMULATION OF OPTIMAL SPEED CONTROL FOR A DC MOTOR USING LINEAR QUADRATIC REGULATOR (LQR)
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This paper describes DC motor speed control based on optimal Linear Quadratic Regulator (LQR) technique. Controller's objective is to maintain the speed of rotation of the motor shaft with a particular step response.The controller is modeled in MATLAB environment, the simulation results show that the proposed controller gives better performance and less settling time when compared with the traditional PID controller.

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Publication Date
Mon May 06 2024
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Using Machine Learning Algorithms to Predict the Sweetness of Bananas at Different Drying Times
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The consumption of dried bananas has increased because they contain essential nutrients. In order to preserve bananas for a longer period, a drying process is carried out, which makes them a light snack that does not spoil quickly. On the other hand, machine learning algorithms can be used to predict the sweetness of dried bananas. The article aimed to study the effect of different drying times (6, 8, and 10 hours) using an air dryer on some physical and chemical characteristics of bananas, including CIE-L*a*b, water content, carbohydrates, and sweetness. Also predicting the sweetness of dried bananas based on the CIE-L*a*b ratios using machine learn- ing algorithms RF, SVM, LDA, KNN, and CART. The results showed that increasing the drying

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Sat Mar 26 2016
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Journal Of Materials Science: Materials In Electronics
Hydrothermal deposition of CdS on vertically aligned ZnO nanorods for photoelectrochemical solar cell application
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Heat transfer enhancement from heat sources using optimal design of combined fins heat-sinks
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Kinetic modeling of a solar photo-electro-Fenton process for treating petroleum refinery wastewater
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Effect of a Nutritional Education Program on Mother Knowledge Regarding Their Children Nutritional Status
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Efficacy of Autogenous Dentin Biomaterial on Alveolar Ridge Preservation: A Randomized Controlled Clinical Trial
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Background. After tooth extraction, alveolar bone resorption is inevitable. This clinical phenomenon challenges dental surgeons aiming to restore esthetic and function. Alveolar ridge preservation can be applied to minimize dimensional changes with a new socket grafting material, an autogenous dentin graft, produced by mechanically and chemically processing natural teeth. This study assessed the safety and efficacy of using autogenous dentin biomaterial in alveolar ridge preservation. Materials and Methods. Patients with nonrestorable maxillary anterior teeth bounded by natural sound teeth were included in this study. After a detailed clinical and tomographic examination, eligible participants were randomly allocated into two groups

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Publication Date
Sun Jan 01 2023
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The Response of Reinforced Concrete Composite Beams Reinforced with Pultruded GFRP to Repeated Loads
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This paper investigates the experimental response of composite reinforced concrete with GFRP and steel I-sections under limited cycles of repeated load. The practical work included testing four beams. A reference beam, two composite beams with pultruded GFRP I-sections, and a composite beam with a steel I-beam were subjected to repeated loading. The repeated loading test started by loading gradually up to a maximum of 75% of the ultimate static failure load for five loading and unloading cycles. After that, the specimens were reloaded gradually until failure. All test specimens were tested under a three-point load. Experimental results showed that the ductility index increased for the composite beams relative to the refe

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Publication Date
Thu May 18 2023
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Bearing Capacity of Shallow Footing on Compacted Filling Dune Sand Over Reinforced Gypseous Soil
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Publication Date
Wed Jan 08 2020
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The local stability of an eco-epidemiological model involving a harvesting on predator population
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In this paper a prey - predator model with harvesting on predator species with infectious disease in prey population only has been proposed and analyzed. Further, in this model, Holling type-IV functional response for the predation of susceptible prey and Lotka-Volterra functional response for the predation of infected prey as well as linear incidence rate for describing the transition of disease are used. Our aim is to study the effect of harvesting and disease on the dynamics of this model.

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