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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 01 2019
Journal Name
Al-khwarizmi Engineering Journal
The Effect of Additives on The Performance of Hydrostatic Thrust Bearings
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The paper is concerned with, the behavior of the hydrostatic thrust bearings lubricated with liquid-solid lubricants using Einstein viscosity formula, and taking into account the centrifugal force resulting from high speed.  Also studied is the effect of the bearing dimensions on the pressure, flow rate, load capacity, shear stress, power consumption and stiffness.

The theoretical results show an increase in load capacity by (8.3%) in the presence of solid graphite particles with concentration of (16%) by weight as compared with pure oil, with increasing shear stress.  .

In general the performance of hydrostatic thrust bearings improve for load carrying capacity, volume flow rate,

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Publication Date
Mon Oct 01 2018
Journal Name
Journal Of Educational And Psychological Researches
Measuring Gratitude of the Sample of Displaced people in Baghdad city
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Displacement is a problem that worries the human conscience and has received the attention of the international community. Furthermore, it has become one of the most urgent issues nowadays, especially when the number of displaced people in different countries are increased because of the causes of displacement and their political, economic, environmental, social and psychological effects. Iraq is one of the countries where displacement has taken place in several governorates, according to United Nations and International Organization for Migration (IOM), Iraq is considered the second largest country in the world after Syria in terms of the number of displaced people in 2015. Gratitude, a positive emotional response to benevolence, is a m

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Publication Date
Mon May 01 2017
Journal Name
2017 5th International Conference On Information And Communication Technology (icoic7)
Analysis of the number of ants in ant colony system algorithm
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Publication Date
Tue Aug 01 2023
Journal Name
Iop Conference Series: Earth And Environmental Science
Evaluation of the Performance of a Locally Manufactured Palm Service Platform
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Abstract<p>A field experiment was carried out in one of the orchards of Al-Qassim district in Babel Governorate to find out the ability of a locally manufactured platform to serve palm trees by working in flat and uneven orchard land, palm tree heights of 4, 8, and 12 meters, and it performs pollination, pruning and harvesting services. The time of ascent and descent, the palm service, and the palm/hour productivity were measured. A randomized complete block design with three replications used a split split-plot arrangement. The nature of the land (flat or uneven) represented the main plots, the height of the palm trees (4, 8, 12) meters, the sub-plots, and the palm service operations (pollinati</p> ... Show More
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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
Thu Mar 30 2023
Journal Name
College Of Islamic Sciences
Description of nature and the joys of life in Fatimid poetry
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This research deals with the aesthetics of describing nature and the joys of urban life in the environment of Fatimid Egypt, among a group of poets, who were deceived by its enchanting beauty and breathtaking scenery, through it they depicted the reality of the life they live, and the things that involved them, as well as showing their personal culture, and the joys of life that experience, articulating this with a descriptive and analytical study, focusing on how the poet portrayed the visual scene, in an important stage of Arabic literature in Egypt.

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Publication Date
Mon Feb 04 2019
Journal Name
Iraqi Journal Of Physics
Environmental study of groundwater in southwest of Baghdad, Yusufiyah using GIS
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Ground water hydrochemical study in Yusufiyah depends upon (25) wells where major cations and anions were obtained as well as trace elements. The hydrochemical properties include the study of (pH, EC, TDS, and TH). The groundwater of the study area is odorless and colorless except the wells (13 and 16) with a salty taste due to the elevated (TDS) concentration in it, where the wells depth ranges between 7-20 meters. Depth of water in these wells was about 25-35 meters above sea level. Groundwater generally flows from east to west and from north east to south west. The resource of groundwater depends upon surface water. Physical specifications are measured in the water samples included temperature, color, taste, odor, pH, electrical condu

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Publication Date
Mon Jul 31 2017
Journal Name
Journal Of Engineering
Effects of Fuel Oil on the Geotechnical Properties of Clay Soil
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Publication Date
Sat Mar 01 2008
Journal Name
Iraqi Journal Of Physics
Effect of Pressure on the Properties of HgBa2Ca2Cu3O8+δ HTSC System
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High temperature superconductors with a nominal composition HgBa2Ca2Cu3O8+δ
for different values of pressure (0.2,0.3, 0.5, 0.6, 0.9, 1.0 & 1.1)GPa were prepared by
a solid state reaction method. It has been found that the samples were semiconductor
P=0.2GPa.while the behavior of the other samples are superconductor in the rang
(80-300) K. Also the transition temperature Tc=143K is the maximum at P is equal to
0.5GPa. X-ray diffraction showed a tetragonal structure with the decreasing of the
lattice constant c with the increasing of the pressure. Also we found an increasing of
the density with the pressure.

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Publication Date
Thu Sep 30 2021
Journal Name
Iraqi Geological Journal
Study of Petrophysical Properties of the Yamama Formation in Siba Oilfield
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Evaluating a reservoir to looking for hydrocarbon bearing zones, by determining the petrophysical properties in two wells of the Yamama Formation in Siba field using Schlumberger Techlog software. Three porosity logs were used to identify lithology using MN and MID cross plots. Shale volume were calculated using gamma ray log in well Sb-6ST1 and corrected gamma ray in well Sb-5B. Sonic log was used to calculate porosity in bad hole intervals while from density log at in-gauge intervals. Moreover, water saturation was computed from the modified Simandoux equation and compared to the Archie equation. Finally, Permeability was estimated using a flow zone indicator. The results show that the Yamama Formation is found to be mainly limest

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