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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
Sun Jun 01 2014
Journal Name
Baghdad Science Journal
Distribution of Some Heavy Metals in Tigris River middle of Iraq
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This study was conducted from February 2010 to December 2010. Water Samples were collected every two months in three stations in Baghdad city. The study involved the assessment of concentrations of some heavy metals such as: Chromium, Cadmium, Copper, Iron, Lead, Manganese, Nickel and Zinc. the values of chromium were undetected for the entire of the study, while the rest of the heavy metal were ranged between 0.001 -0.438 mg / l, ND -0.077 mg / L, ND -0.778 mg / l, 0.36 - 0.011 mg / l, 0.011-0 .08mg/ l, ND - 0.1985 mg / l, ND -0.0416 mg / l, respectively. The results showed that the concentrations of heavy metals were fluctuated during the study period, except Lead which have high concentrations and exceeded the permit limits in all statio

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Publication Date
Sun Aug 30 2020
Journal Name
Journal Of Economics And Administrative Sciences
The Influence of Emotional Intelligence in promoting the Empowerment of Employees
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The subject of the research seeks to indicate the level of influence of emotional intelligence in the empowerment of workers in the Ministry of Industry and Minerals General Company for Food Products. The research problem is illustrated by knowing all of the following:

  • The level of the relationship between emotional intelligence in promoting the empowerment of employees of the Ministry of Industry and Minerals.
  • The impact of emotional intelligence on the empowerment of workers in the ministry.
  • Recognize the interest of the management of the Ministry of Industry and Minerals in emotional intelligence and the

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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
Sun Dec 01 2019
Journal Name
2019 Ieee Asia-pacific Conference On Computer Science And Data Engineering (csde)
Effect of Clay Content on Performance of a Crushed Rock Mix
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Publication Date
Mon Oct 01 2012
Journal Name
Journal Of Engineering
Prediction of Smear Effect on the Bearing Capacity of Driven Piles
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This paper deals with prediction the effect of soil re-moulding (smear) on the ultimate bearing capacity of driven piles. The proposed method based on detecting the decrease in ultimate bearing capacity of the pile shaft (excluding the share of pile tip) after sliding downward. This was done via conducting an experimental study on three installed R.C piles in a sandy clayey silt soil. The piles were installed so that a gap space is left between its tip and the base of borehole. The piles were tested for ultimate bearing capacity according to ASTM D1143 in three stages. Between each two stages the pile was jacked inside the borehole until a sliding of about 200mm is achieved to simulate the soil re-moulding due to actual pile driving. The re

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Publication Date
Fri Oct 01 2010
Journal Name
Iraqi Journal Of Physics
The axial profile of plasma characteristics of cylindrical magnetron sputtering device
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In the present work, a d.c. magnetron sputtering system was designed and fabricated. The chamber of this system was includes from two copper coaxial cylinders where the inner one used as a cathode (target) while the outer one used as the anode with Solenoid magnetic coil located on the outer cylinder (anode). The axial profile of magnetic field for various coil current (from 2A to 14 A) are shown. The plasma characteristics in the normal glow discharge region are diagnostics by the 2.2mm diameter Langmuir probe with different length along the cathode and located at different radial positions 1cm and 2cm from the cathode surface. The result of this work shows that, the electron energy distributions at different radial positions along the

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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 Aug 01 2016
Journal Name
Journal Of Engineering
Preparation and Characterization of Activated Carbon for Adsorption of Fluoroquinolones Antibiotics
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           In this research, the preparation of a chemically activated carbon from date stones by using electric and microwave assisted K2CO3 activation was studied. The effect of radiation power, radiation time, and impregnation ratio on the yield and Iodine number on the activated carbons was investigated. The activated carbon characterizations were examined by its surface area, pore structure analysis, bulk density, moisture content, ash content, iodine number, FTIR, and scanning electron microscopy (SEM). The adsorption capacity was also studied by adsorption of fluoroquinolones antibiotics, CIP, NOR, and LEVO, by the prepared activated carbon.

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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 May 01 2017
Journal Name
International Journal Of Applied Pharmaceutics
DEVELOPMENT AND PHYSICAL CHARACTERIZATION OF A PERIODONTAL BIOADHESIVE GEL OF GATIFLOXACIN
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Objective: The aim of this study was to develop a bioadhesive gel of gatifloxacin for the treatment of periodontal diseases.Methods: Periodontal gels of gatifloxacin were prepared using different hydrophilic polymers such as carbopol 940 (CP 940), carboxymethyl cellulose (CMC) and hydroxypropylmethyl cellulose (HPMC) in varied concentrations, either alone or as a combination. The prepared gels were evaluated for their physical appearance, pH, drug content, viscosity, bioadhesiveness and in vitro drug release profile. The influence of the type and the concentration of polymer on the drug release as well as on viscosity and mucoadhesiveness of prepared gels were investigated.Results: The prepared gels showed acceptable physical proper

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