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Investigation of Solubility Enhancement Approaches of Ticagrelor
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ABSTRACT

                   Ticagrelor is an orally administered antiplatelet medicine, direct-acting P2Y12-receptor antagonist. Ticagrelor binds reversibly and noncompetitively to the P2Y12 receptor at a site distinct from that of the endogenous agonist adenosine diphosphate (ADP). Inhibition of platelet aggregation stimulated by ADP is a commonly used pharmacodynamic parameter for P2Y12-receptor antagonists.

                  Ticagrelor is a crystalline powder with an aqueous solubility of approximately 10?g/mL at room temperature. Ticagrelor exhibits no pKa value within the physiological range. Ticagrelor does not exhibit pH-dependent solubility and is defined as ‘low solubility low permeability’ under the Biopharmaceutics Classification System (Class IV). The mean absolute bioavailability of ticagrelor in healthy volunteers is 36 %

                   Nanoparticles preparation and complexation is one of the recently used approaches to enhance the solubility of drugs. The aim of the present work was to improve the solubility and dissolution of ticagrelor by preparing nanoparticles and cyclodextrin inclusion complex of ticagrelor and then incorporated in to tablet dosage form. Fifteen formulas of nanoparticles were prepared by antisolvent precipitation method (solvent displacement method) utilizing one of the three polymers (PVP, Poloxamer, and HPMC) at three different drugs: polymer and solvent: anti-solvent ratios and nine formulas of cyclodextrin inclusion complex with HP?CD  by three preparation methods, physical trituration, kneading and solvent evaporation, which increase the solubility and dissolution rate of ticagrelor via formation of inclusion complex with HP?CD.

              The prepared formulas were characterized regarding the saturated solubility, polydispersity index, particle size by nano laser particle size analyzer, % yield, entrapment efficiency, and flowability, FTIR, DSC, and SEM. The selected formulas were prepared as tablets.

             The prepared tablets were evaluated for drug content, weight variation, hardness, and friability. In vitro dissolution data of the prepared tablets were analyzed using similarity factor (f2) and dissolution efficiency (DE).  

           Among all the prepared nanoparticles formulas, formula (F12) which contain HPMC as a polymer at polymer: drug ratio of (1:1) and solvent: antisolvent ratio of (1:1) was considered as the optimum formula which shows good evaluation parameters in addition to the increment in the solubility to about 9 times than that of the pure drug. The nanoparticle of the selected formula (F12) incorporated tablets showed an acceptable tablet properties in addition to a considerable increase in the dissolution efficiency to (DE=92 % and 88 % in PH 1.2 and PH 6.8 respectively) in comparison to that of the marketed tablet (DE=89% and 85% in PH 1.2 and PH 6.8 respectively).  Moreover, the analysis by DSC and SEM of the nanoparticles of the selected formula (F12) indicate a reduction in the crystallinity and amorphization of the drug. It can be concluded that the selected formula is a promising formula for the preparation of ticagrelor nanoparticles the incorporation in a tablet dosage form.

          Regarding ticagrelor inclusion complex with HP?CD Solvent evaporation method was the most effective method regarding ticagrelor solubilization and optimum formula of inclusion complex (F23) show increment in saturated solubility about ten times that of pure drug.

          The ticagrelor inclusion complex of the selected formula (F23) incorporated tablets showed an acceptable tablet properties in addition to a considerable increase in the dissolution efficiency to (DE=92 % and 90 % in PH 1.2 and PH 6.8 respectively) in comparison to that of the marketed tablet (DE=89% and 85% in PH 1.2 and PH 6.8 respectively).  

 

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Publication Date
Fri Feb 01 2013
Journal Name
Journal Of Engineering
Estimation of Flexural Strength of Plain Concrete from Ultrasonic Pulse Velocity
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The aim of this study is to propose mathematical expressions for estimation of the flexural strength of plain concrete members from ultrasonic pulse velocity (UPV) measurements. More than two hundred pieces of precast concrete kerb units were subjected to a scheduled test program. The tests were divided into two categories; non-destructive ultrasonic and bending or rupture tests. For each precast unit, direct and indirect (surface) ultrasonic pulses were subjected to the concrete media to measure their travel velocities. The results of the tests were monitored in two graphs so that two mathematical relationships can be drawn. Direct pulse velocity versus the flexural strength was given in the first relationship while the second equation des

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Publication Date
Wed Dec 30 2015
Journal Name
College Of Islamic Sciences
Rhetoric of the ellipses   In the poetry of Namik Abdul Deeb
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The research attempts to identify the pattern of punctuation in contemporary Iraqi poetry through delving into the poetry of an Iraqi poet belonging to the seventieth generation, Namik Abdul Deeb, who belongs to the poets of Arab modernity in general, the research has reached many results, including that the signs of deletion were vocabulary marks any They are located in the center of the poetic singular, or inline markers, which are those that fall within the poetic line of the prose poem separating its vocabulary, or cross-sectional marks located within the poetic passages that are part of the poetic text, and finally text marks which are located within the poetic text and fragmented into Parts. The research also found that the work of

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Publication Date
Wed Dec 30 2020
Journal Name
Journal Of Planner And Development
The preferences of planning bridges of Al-Mosul city post war
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The study started from the problems of wars and the damage that result from deterioration and destruction of infrastructure and the absence of planning and urban reconstruction. The study aims to address the condition of the bad destroyed bridges that have paralyzed traffic from the right and left sides of the city of Mosul. The study is based on the assumption that the reconstruction of bridges will improve the transportation network in the city of Mosul. The study relied on several approaches, including: the historical approach by reviewing global and local experiences and the descriptive approach to review the reality of the state of Mosul after the liberation process, through maps and the analytical approach through statistics and da

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Publication Date
Mon Jan 01 2018
Journal Name
Indian Journal Of Public Health Research & Development
Effects of Silver Nanoparticles on Biofilms of <i>Streptococcus</i> Spps
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Today technology using nanoparticle when treatment pathogentic microorganism and we focused on this here. It was found that the species of streptococcus used in present study were sensitive to erythromycin. In present study focusing biofilm formation by Streptococcus spp was evaluated. Species S. mutans was found that highest amount of biofilm compare with the other species. The aim of report effect (SNPs) on ability of biofilm form different species of streptococcus. The anti-biofilm effect of SNPs was in concentration dependent manner. The highest effect of SNP against biofilm formation was found the concentration 160 μg/ml, while the lowest effect was found the lowest used concentration (80 μg/ml) of SNPs. In vivo study revealed that s

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Publication Date
Mon Aug 01 2011
Journal Name
Journal Of Engineering
IMPLEMENTATION OF ROOT FINDING ALGORITHM OF MINIMUM PHASE FILTER USING VHDL
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Root-finding is an oldest classical problem, which is still an important research topic, due to its impact on computational algebra and geometry. In communications systems, when the impulse response of the channel is minimum phase the state of equalization algorithm is reduced and the spectral efficiency will improved. To make the channel impulse response minimum phase the prefilter which is called minimum phase filter is used, the adaptation of the minimum phase filter need root finding algorithm. In this paper, the VHDL implementation of the root finding algorithm introduced by Clark and Hau is introduced.
VHDL program is used in the work, to find the roots of two channels and make them minimum phase, the obtained output results are

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Publication Date
Fri May 01 2015
Journal Name
2015 International Symposium On Mathematical Sciences And Computing Research (ismsc)
Analysis of significant dimensions of e-service quality in Malaysian universities
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Publication Date
Sat Feb 14 2015
Journal Name
Global Journal Of Advanced Engineering Technologies And Sciences
EVALUATION OF ANTIBACTERIAL ACTIVITY OF METAL NANOPARTICLES AGAINST DIFFERENT PATHOGENIC BACTERIA
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In recent years, infectious diseases are increasingly being encountered in clinical settings. Due to the development of antibiotic resistance and the outbreak of these diseases caused by resistant pathogenic bacteria, the pharmaceutical companies and the researchers are now searching for new unconventional antibacterial agents. Recently, in this field, the application of nanoparticles is an emerging area of nanoscience and nanotechnology. For this reason, nanotechnology has a great deal of attention from the scientific community and may provide solutions to technological and environmental challenges. A common feature that these nanoparticles exhibit their antimicrobial behavior against pathogenic bacteria. In this report, we evaluate

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Publication Date
Mon Mar 27 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis and Antibacterial Activity of bis Heterocyclic Derivatives of 1,3,4-thiadiazole
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The Chemistry of heterocyclic sulphur and nitrogen containing compounds have a great role in the  field of scientific studies, The 2-amino 5-mercapto-1,3,4-thiadiazole ring for instance, has gained more importance in recent years because  they are considered as potent biologically active nucleus. In this study disulfide derivative can be obtained by oxidation with hydrogen peroxide of thiol group of the heterocyclic 2-amino 5-mercapto-1,3,4-thiadiazole ring to obtain compound (3) with expected antibacterial  activity. In order to use it as a diazo component to prepare some new bis azo compounds as possible antibacterial  agents, the reaction of two primary amino groups on both sides of disulfide dimer with sodium nitr

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Publication Date
Sun Jun 30 2013
Journal Name
Al-khwarizmi Engineering Journal
Estimation of SNR Including Quantization Error of Multi-Wavelength Lidar Receiver
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 This paper comprises the design and operation of mono-static backscatter lidar station based on a pulsed Nd: YAG laser that operates at multiple wavelengths. The three-color lidar laser transmitter is based on the collinear fundamental 1064 nm, second harmonic 532 nm and a third harmonic 355nm output of a Nd:YAG laser. The most important parameter of lidar especially daytime operations is the signal-to-noise ratio (SNR) which gives some instructions in designing of lidar and it is often limit the effective range. The reason is that noises or interferences always badly affect the measured results. The inversion algorithms have been developed for the study of atmospheric aerosols. Signal-to-noise ratio (SNR) of three-color channel re

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Publication Date
Fri Jul 01 2022
Journal Name
Journal Of Engineering
Influence of Stone Powder on the Mechanical Properties of Clayey Soil
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In this experimental study, the use of stone powder as a stabilizer to the clayey soil studied. Tests of Atterberg limits, compaction, fall cone (FCT), Laboratory vane shear (LVT), and expansion index (EI) were carried out on soil-stone powder mixtures with fixed ratios of stone powder (0%, 5%, 10%, 15%, and 20%) by the dry weight. Results indicated that the undrained shear strength obtained from FCT and LVT increased at all the admixture ratios, and the expansion index reduced with the increase of the stone powder.

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