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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 Mar 01 2009
Journal Name
Al-khwarizmi Engineering Journal
Numerical Computations of Transonic Critical Aerodynamic Behavior of a Realistic Artillery Projectile
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The determination of aerodynamic coefficients by shell designers is a critical step in the development of any projectile design. Of particular interest is the determination of the aerodynamic coefficients at transonic speeds. It is in this speed regime that the critical aerodynamic behavior occurs and a rapid change in the aerodynamic coefficients is observed. Two-dimensional, transonic, flow field computations over projectiles have been made using Euler equations which were used for solution with no special treatment required. In this work a solution algorithm is based on finite difference MacCormack’s technique for solving mixed subsonic-supersonic flow problem. Details of the asymmetrically located shock waves on the projectiles hav

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Sat Feb 01 2020
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Journal Of Economics And Administrative Sciences
Use Pareto Chart to diagnose the level of quality of municipal services
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The aim of the study is to study the quality of services in a sample of the municipalities of Baghdad governorate and identify the deviations in their operations and provide solutions to address the causes of deviations. The research field aims at the same activity related to municipal services and their quality and analysis using some tools for continuous improvement to identify the authorities responsible for the delay and quality of services. In the future, the importance of research is shown by the use of these tools and their use and their application to the data of the directorates (sample of the study) to diagnose and treat problems, especially that they include statistical methods that are clear and easy to understand the

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Mon Jun 01 2015
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The Philosophy of Organizational Forgetting In Frame of Learning and Organizational knowledge
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current research aims to build an intellectual framework for concept of organizational forgetting, which is considered one of the most important topics in contemporary management thought, which is gain the consideration of most scholars and researchers in field of organizational behavior, which is to be a loss of intentional or unintentional knowledge of any organizational level. It turned out that just as organizations should learn and acquire knowledge, they must also forget, especially knowledge obsolete and worn out. And represented the research problem in the absence of Arab research dealing with organizational forgetting, and highlights the supporting infrastructure core, and show a close relationship with organizational le

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Publication Date
Tue Mar 12 2019
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Optimization of Diffusion Bonding of Pure Copper (OFHC) with Stainless Steel 304L: .
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This work deals with determination of optimum conditions of direct diffusion bonding welding of austenitic stainlesssteel type AISI 304L with Oxygen Free High Conductivity (OFHC) pure copper grade (C10200) in vacuum atmosphere of (1.5 *10-5 mbr.). Mini tab (response surface) was applied for optimizing the influence of diffusion bonding parameters (temperature, time and applied load) on the bonding joints characteristics and the empirical relationship was evaluated which represents the effect of each parameter of the process. The yield strength of diffusion bonded joint was equal to 153 MPa and the efficiency of joint was equal to 66.5% as compared with hard drawn copper. The diffusion zone reveals high microhardness than coppe

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Sat Oct 01 2022
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NEWS COVERAGE OF THE TORTURE SCANDAL OF DETAINEES AT ABU GHRAIB PRISON
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According to the topics of study, The intensity of the news coverage of the Abu Ghraib scandal and the US soldiers' torture of Iraqi prisoners have become apparent since the scandal was revealed on April 29, 2004 until May 30, 2004 and the period in which the coverage of this scandal had intensified not only in Al-Zaman, but in all newspapers, magazines and other media locally and internationally. And according to a research taken from Al-Zaman magazine that showed great interest in highlighting the event, interpreting it, following up its roots and results, and showing contradictory claims and slogans between the US and Britain, particularly in respecting human rights and the spread of justice, equality and well-being in Iraq specifical

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Thu Jul 01 2021
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Evaluation of some biomarkers in diagnosis of bacterial bloodstream infection in children
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Background Bloodstream infection (BSI) is a life-threatening condition caused by the presence of microorganisms, generally caused by a range of bacteria in the blood. Objectives The aim of this study was to evaluate the possible role of procalcitonin (PCT) and C-reactive protein (CRP) as biomarkers of pediatric BSI. Methodology The study was conducted on 150 blood samples collected from the patient who admitted to Children Welfare Teaching Hospital, Medical City, Baghdad. During the period from November 2020 to March 2021, ninety blood samples from them were positive culture and 60 blood samples were negative culture (control group). The isolates were identified depending on the morphological, microscopic examination, and biochemical tests.

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Publication Date
Wed Oct 16 2019
Journal Name
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Assessing quality of life among sample of iraqi patients with rheumatoid arthritis
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Rheumatoid arthritis is one of the common chronic disease, which lead to great disability and chronic pain, and has a main adverse economic and social effect upon patients. The reason for the addition of quality of life as a pointer for health outcome result is attributed to the affectability of this measure for the evaluation of patient's health status after taken treatment and its health outcome. The purpose of the current study was to assess quality of life among a sample of Iraqi patients with rheumatoid arthritis and to determine the possible association between health’s related quality of life and some patient-certain factors. This study is a cross-sectional study carried out on 250 already diagnosed rheumatoid arthritis pat

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Publication Date
Thu Jan 30 2020
Journal Name
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Calculation of Pressure Loss of Two Drilling Muds in Noor Oil Field
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In this work, calculation of pressure losses in circulating system for two drilling muds is evaluated in Noor oil field. Two types of drilling muds that were used for drilling section 12 1/4" and 8 3/4" which are Salt saturated mud and Ferro Chrome Lignosulfonate-Chrome Lignite mud. These calculations are based on field data that were gathered from the drilling site of well Noor-15, which are included, rheological data, flow data and specification of drill string. Based on the obtained results, the best rheological model that fit their data is the Herschel-Bulkley model according to correlation coefficient value for their two drilling mud. Also, the difference between the calculated pressure lo

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Effect of phosphorous and amino acid on growth and yield of pea
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Mon Oct 01 2012
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Influence of substrate temperature on structural and optical properties of SnO2 films
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Tin Oxide (SnO2) films have been deposited by spray pyrolysis technique at different substrate temperatures. The effects of substrate temperature on the structural, optical and electrical properties of SnO2 films have been investigated. The XRD result shows a polycrystalline structure for SnO2 films at substrate temperature of 673K. The thickness of the deposited film was of the order of 200 nm measured by Toulansky method. The energy gap increases from 2.58eV to 3.59 eV when substrate temperature increases from 473K to 673K .Electrical conductivity is 4.8*10-7(.cm)-1 for sample deposited at 473K while it increases to 8.7*10-3 when the film is deposited at 673K

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