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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
Thu May 06 2021
Journal Name
Tesol International Journal
The Effect of Types of Blended Learning Strategies on EFL Students` Achievements
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This work aims at finding out the impact of teaching types blended learning strategies on academic students` achievement. A review of related literature indicates that almost no study has ever attempted to focus specifically on the effect of the different kinds of blended learning strategies on EFL students` achievement in the educational research writing, and the present study attempts to fill this gap. The study focused on the students at the Master's degree in Educational Research Writing in the first semester of the academic year 2020/2021. The sample has selected from the college of Education Ibn-Rushd (18) students. Material has been designed for the Master candidates’ participants of the study was divided into two groups: one an e

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Evaluation of Hemolysis Activity of Zerumbone on RBCs and Brine Shrimp Toxicity
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Zerumbone is a well-known compound having anti-cancer, anti-ulcer, anti-inflammatory and anti-hyperglycemic effects. During its use for the disease treatment, the membrane of erythrocyte can be affected by consumption of this bioactive compound. The current study was the first report of investigation of the hemolytic activities on human erythrocytes and cytotoxic profile of zerumbone. The toxicity of zerumbone on human erythrocytes was determined by in vitro hemolytic assay. Brine shrimp lethality assay was used to evaluate the cytotoxic effect of zerumbone at concentrations 10, 100 and 1000 μg/mL. The human erythrocyte test showed no significant toxicity at low concentrations, whereas hemolytic effect was amplified up to 17.5 % at

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Publication Date
Wed Nov 30 2022
Journal Name
Iraqi Journal Of Science
Synthesis and Characterization of Ni2O3 as a Phase of Nickel Oxide Nanomaterial
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    Ni2O3 nanomaterial, a phase of nickel oxide, is synthesized by a simple chemical process. The pure raw materials used in the present process were nickel chloride hexahydrate NiCl2.6H2O and potassium hydroxide KOH by utilizing temperature at 250 oC for 2 hour.  The structural, morphological and optical properties of the synthesized specimens of Ni2O3 were investigated employing diverse techniques such as XRD, AFM, SEM and UV-Vis, respectively. The XRD technique confirms the presence of Ni2O3 nanomaterial with crystal size of 57.083 nm which indexing to the (2θ) of 31.82; this results revealed the Ni2O3 was a phase of nickel oxide with Nano structure. The synthesized Ni2O3 will be useful in manufacturng electrodes materials f

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Publication Date
Sat Jan 09 2016
Journal Name
مجلة العلوم التربوية والنفسية
Hill, the Employment of a Specimen in the Teaching of Arabic Grammar
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Publication Date
Sun Jan 06 2013
Journal Name
Journal Of Educational And Psychological Researches
The reality of teaching performance materials for teachers of social primary stage
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Publication Date
Sat Jun 30 2001
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Kinetics of Sodium Tungstate Catalyzed Oxidation of Maleic Acid by Hydrogen Peroxide
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Publication Date
Mon Sep 30 2002
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Effect of using Two Binders on the Agglomeration of Zeolite Type 4A
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Publication Date
Thu Dec 01 2011
Journal Name
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Measurement of Impact of Banking System Development on Economic Growth in Iraq
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At the heart of every robust economy is a vital banking system. The functional banking system can effectively perform several functions such as mobilizing savings, allocating credit, monitoring managers, transforming risks, and facilitating the financial transactions. This paper aims to measure the impact of banking system development on economic growth in Iraq. Credit to private sector divided by GDP used as a proxy of banking development. Real per capita GDP used as a proxy of economic growth. By using Autoregressive Distributed Lag (ARDL) model, the paper finds that the undeveloped Iraqi banking system could not promote economic growth in the country. Therefore, a variety of policies need to be taken to spur the role of bankin

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Publication Date
Sat Aug 01 2015
Journal Name
Journal Of Engineering
Influence of Internal Sulfate Attack on Some Properties of High Strength Concrete
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One of the most important problems that faces the concrete industry in Iraq is the deterioration due to internal sulfate attack , since it  reduces the compressive strength and increases the expansion of concrete. Consequently, the concrete structure may be damage .The effects of total and total effective sulfate contents on high strength concrete (HSC) have been studied in the present study.

The research studied the effect of sulfate content in cement , sand and gravel , as well as comparing  the total sulfate content with the total effective SO3 content. Materials used were divided into two groups of SO3 in cement ,three groups of SO3 in sand ,and two groups of SO

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Publication Date
Wed Jul 01 2015
Journal Name
Journal Of Engineering
Studying of Some Mechanical Properties of Reactive Powder Concrete Using Local Materials
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This research aims to investigate and evaluate a reactive powder concrete (RPC) cast using economical materials. Its mechanical properties were investigated and evaluated by studying the effects of using different cement and silica fume contents and locally steel fibers aspect ratios as reinforcement for this concrete. A compressive strength of about 155.2MPa, indirect tensile strength of 16.0MPa, modulus of elasticity of 48.7GPa, flexural strength of 43.5MPa, impact energy of 3294.4kN.m and abrasion loss 0.59%  have been achieved for reinforced RPC contains  910 kg/m3 cement content, silica fume content 185 kg/m3 of cement weight and fiber volume fraction 2%. The water absorption values w

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