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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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Thu May 31 2012
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Al-khwarizmi Engineering Journal
Channel Estimation and Prediction Based Adaptive Wireless Communication Systems
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Wireless channels are typically much more noisy than wired links and subjected to fading due to multipath  propagation which result in ISI and hence high error rate. Adaptive modulation is a powerful technique to improve the tradeoff between spectral efficiency and Bit Error Rate (BER). In order to adjust the transmission rate, channel state information (CSI) is required at the transmitter side.

In this paper the performance enhancement of using linear prediction along with channel estimation to track the channel variations and adaptive modulation were examined. The simulation results shows that the channel estimation is sufficient for low Doppler frequency shifts (<30 Hz), while channel prediction is much more suited at

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Publication Date
Mon Feb 04 2019
Journal Name
Journal Of The College Of Education For Women
Image Watermarking based on Huffman Coding and Laplace Sharpening
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In this paper, an algorithm through which we can embed more data than the
regular methods under spatial domain is introduced. We compressed the secret data
using Huffman coding and then this compressed data is embedded using laplacian
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threshold value we found the places with the highest values acquired from these filters
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increasing the security of the algorithm by hiding data in the places that have highest
values of edges and less noticeable.
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Publication Date
Sat Oct 01 2011
Journal Name
Journal Of Engineering
IMPROVED IMAGE COMPRESSION BASED WAVELET TRANSFORM AND THRESHOLD ENTROPY
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In this paper, a method is proposed to increase the compression ratio for the color images by
dividing the image into non-overlapping blocks and applying different compression ratio for these
blocks depending on the importance information of the block. In the region that contain important
information the compression ratio is reduced to prevent loss of the information, while in the
smoothness region which has not important information, high compression ratio is used .The
proposed method shows better results when compared with classical methods(wavelet and DCT).

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Tue Oct 18 2022
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Plain, Edge, and Texture Detection Based on Orthogonal Moment
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Image pattern classification is considered a significant step for image and video processing. Although various image pattern algorithms have been proposed so far that achieved adequate classification, achieving higher accuracy while reducing the computation time remains challenging to date. A robust image pattern classification method is essential to obtain the desired accuracy. This method can be accurately classify image blocks into plain, edge, and texture (PET) using an efficient feature extraction mechanism. Moreover, to date, most of the existing studies are focused on evaluating their methods based on specific orthogonal moments, which limits the understanding of their potential application to various Discrete Orthogonal Moments (DOM

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Wed Jul 04 2012
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Azithomycin as an adjunctive to non-surgical treatment in comparison with doxycycline in chronic periodontitis patients: 2-months randomized clinical trial
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Wed Dec 15 2021
Journal Name
Arab World English Journal
Reading Difficulties in English as a Second Language in Grade Five at a Saint Patrick’s High School for Boys, Hyderabad- India
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Reading is one of the essential components of the English language. Countries that use English as a second language (ESL) sometimes have difficulties in reading and comprehension. According to many researches, mother tongue has proved some interferences with learning a second language. This study investigated the results of reading difficulties of young second language learners in terms of accuracy, comprehension, and rate using the Neale Analysis of Reading Ability test. The study was carried out in one of the High Schools for Boys in Hyderabad, India and included Grade five, aged 10-12 years. In order to understand the reading difficulties of English as a second language, a qualitative approach was employed. Interview, reading tes

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Publication Date
Mon Mar 13 2017
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Thu Mar 30 2017
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AComparative Qualitative and Quantitative Study of Anthraquinone Derivatives in the Roots of Rheum ribes and Rheum emodi by HPLC
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Sun Feb 03 2019
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beginning the Paleolithic until the later period , and to understand the environment ,
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human behavior from choosing , the settlement sits and than ( we could ) knowledge
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Publication Date
Thu Nov 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
The Impact of Technological Change in Process Design Decisions (Applied study in an organization)
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Abstract:

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