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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 Mar 31 2017
Journal Name
Al-khwarizmi Engineering Journal
Improvement of Dynamic Buckling Behavior of Intermediate Aluminized Stainless Steel Columns
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This paper experimentally investigated the dynamic buckling behavior of AISI 303 stainless steel aluminized and as received intermediate columns.  Twenty seven specimens without aluminizing (type 1) and 75 specimens with hot-dip aluminizing at different aluminizing conditions of dipping temperature and dipping time (type 2), were tested under dynamic compression loading (compression and torsion), dynamic bending loading (bending and torsion), and under dynamic combined loading (compression, bending, and torsion) by using a rotating buckling test machine. The experimental results werecompared with tangent modulus theory, reduced modulus theory, and Perry Robertson interaction formula. Reduced modulus was formulated to circular cross-

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Publication Date
Fri Jun 30 2023
Journal Name
College Of Islamic Sciences
Moderation between the anvil of application and the hammer of extremism
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This research study focuses on fundamental questions. It deals with the content of the critical reviews through which the most important sources that undermine the renaissance of the Islamic human society can be concluded. It is the vague fetishization of the sacred between religion, politics, and ideas, which members of society live in  and which raised the dust of closed-minded fanaticism that led to the return of deviant extremism. It is oppression, violence, and domination, all of which are professional tools in the manufacture of the ideology of extremism in all its forms. Here,  the idea matured in giving a human, intellectual and philosophical overview that mixed the required drawing in the formulation of scientific cont

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Publication Date
Tue Mar 30 2021
Journal Name
Baghdad Science Journal
Insecticidal Activity of Some Chemicals of Mosquitoes Culex pipiens molestus Forskal
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   The chemicals materials were used to study the effect of citric acid, detergents, sodium carbonate, sodium bicarbonate on the vitality of the third stage of mosquito Culex pipiens molestus. The highest larvicidal efficacy was established from citric acid solution followed by detergents solution, sodium carbonate, sodium bicarbonate with (LC50) values 2096, 2715, 13930, 13960 ppm respectively. The concentration of 1000 ppm of citric acid showed a fatal effect on the third stage larvae of mosquitoes which gave a mortality percent of 100% on the second day of the treatment. It was followed by the concentrations of 750 ppm and 500 ppm respectively which caused the death of all larvae on the fifth and sixth days respe

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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
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 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
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Some properties of the Osvillatory and nonoscillatory solutions of second order
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in this paper sufficient conditions of oscillation of all of nonlinear second order neutral differential eqiation and sifficient conditions for nonoscillatory soloitions to onverage to zero are obtained

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Crossref
Publication Date
Tue Dec 01 2015
Journal Name
Journal Of Engineering
The Role of Transition of Workforce between Companies in Transferring Technology
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The transition of professionals between different sectors is considered as one of sources of
acquisition of technology and will lead to add the practical experience to them. This experience
depending on different factors like: the scientific degree and practical experience by the
professionals, the technology possessed by the transferor sector, the duration that spent by
experienced in transferor sector, the type of work performed by professional….etc.
The research aims to verify the affect of these factors in technology transfer process.
Research reached that the technology transfer process which is depending on the Iraqi competencies
in work is unsatisfied level between Iraqi organizations because there are dif

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Publication Date
Sat Jun 01 2013
Journal Name
Journal Of The College Of Languages (jcl)
Violation of the Strategies of Conversation in Some English Selected Plays
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The present study analyzes the violation of the strategies of conversation in two English plays namely Richard II and King Lear. The present study tries to achieve the following goals: 1. showing how the strategies of real conversation can be applied to conversation in plays. 2. analyzing how the characters communicate with each other to discover how Shakespeare violates the strategies of conversation in depicting his characters. The study has been conducted on the bases of the following hypotheses:

  1. The strategies of conversation which are derived from the study of natural conversation can be applied to conversation in drama with some modification for dramatic purposes.

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