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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 Sep 09 2021
Journal Name
Turkish Journal Of Physiotherapy And Rehabilitation,
The Violation of Religious Human Rights: A sample Analysis of an Offensive Image of Islamic Concept
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The purpose of this paper is to investigate Religious Human Rights Violations. Religious liberty is essential for everyone, everywhere. Because religion is significant to everyone, everywhere. Humans are religious by nature. Our nature drives us to seek answers to deep questions about ultimate things. We cannot live a fully human life unless we are free to seek those answers and live according to the truths we discover. In this study, the researcher used Marsh and White model for analysis A sample of an offensive image of an Islamic concept from the book "Mohammad believes it or else." this book is a comic book written by pseudonym Abdullah Aziz and published by Crescent Moon Publishing company. The book is marked with anti- Mohammad, preju

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Publication Date
Tue Oct 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
Comparison of some robust methods in the presence of problems of multicollinearity and high leverage points
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The multiple linear regression model of the important regression models used in the analysis for different fields of science Such as business, economics, medicine and social sciences high in data has undesirable effects on analysis results . The multicollinearity is a major problem in multiple linear regression. In its simplest state, it leads to the departure of the model parameter that is capable of its scientific properties, Also there is an important problem in regression analysis is the presence of high leverage points in the data have undesirable effects on the results of the analysis , In this research , we present some of

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Publication Date
Thu Nov 28 2024
Journal Name
Journal Of Emergency Medicine, Trauma And Acute Care
Assessment of practices and attitudes of undergraduate students toward family violence in the University of Baghdad
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Objectives: The aim of this study was to assess undergraduate student's practices and attitudes toward family violence in the University of Baghdad.

Methods: This was a descriptive study on non-probability (purposive) sample of 100 undergraduate students from different colleges at the University of Baghdad from November 15, 2022 to May 20, 2023. A validated questionnaire was prepared with 43 questions, which consisted of three parts: eight items related to students’ demographic data, 13 items related to students’ attitudes, and 22 items related to students’ practices.

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Publication Date
Sat Jan 01 2022
Journal Name
Iraqi Journal Of Science
Determination of Magnitudes and Orientation of the Paleostress of Bekhme Structure in Shaqlawa area, Northerneastern Iraq
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This study presents determination of the paleostress magnitudes and orientation of Bekhme Structure in Shaqlawa area northeastern Iraq. Paleostress Analysis of slip-fault measurements is performed using Right dihedral, Lisle diagram and Mohr Circles methods. Depending on Mohr Circles, Bott law and vertical thickness, the magnitudes of the paleostress at the time of the tectonic activity were determined. Firstly, Georient Software was used to estimate the orientation of the paleostresses (σ1, σ2 and σ3). Secondly, using the rupture –friction law, taking into account depth of the overburden and the vertical stress (σv) was calculated to determine the magnitude of the paleostresses (σ1=4500 bars, σ2=1

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Publication Date
Wed Dec 30 2020
Journal Name
Biodiversitas Journal Of Biological Diversity
Assessment of some heavy metals in various aquatic plants of Al-Hawizeh Marsh, southern of Iraq
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Abstract. Al-Abbawy DAH, Al-Thahaibawi BMH, Al-Mayaly IKA, Younis KH. 2021. Assessment of some heavy metals in various aquatic plants of Al-Hawizeh Marsh, southern of Iraq. Biodiversitas 22: 338-345. In order to describe the degree of contamination of aquatic environments in Iraq, heavy metals analysis (Fe, Ni, Cr, Cd, Pb, and Zn) was conducted for six aquatic macrophytes from different locations of Al-Hawizeh Marsh in southern Iraq. The six species were Azolla filiculoides (floating plant), Ceratophyllum demersum, Potamogeton pectinatus, Najas marina (submerged plants), Phragmites australis, and Typha domingensis (emergent plants). The results indicate that cadmium, chromium, and iron concentrations in aquatic plants were above the

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Publication Date
Thu May 01 2014
Journal Name
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The effects of different doses of silibinin in combination with methotrexate on testicular tissue of mice
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Methotrexate (MTX) is widely used chemotherapeutic agent with different side effects including germ cells toxicities. Silibinin is one of the structural isomers of silymarin, with different phytotherapeutic applications, and its possible protective effects against MTX induced germ cells damage were investigated in this work. Twenty five male mice were divided into five groups (n=5) allocated as follows: Group 1 received buffer for five days given by single intraperitoneal (IP) injection per day; Group 2 in addition to buffer for five days, animals received at day five single dose of 20mg/kg of MTX IP. Groups (3, 4, and 5) received respectively, (50, 100, or 150mg/kg body weight) of silibinin IP single daily dose for five days then at day fi

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Publication Date
Sun Jan 01 2023
Journal Name
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Enhancing Photostability Of Maxillofacial Silicone By The Addition Of Ultraviolet Absorbing Bisoctrizole:, A Review Of Literature
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Publication Date
Mon Aug 15 2011
Journal Name
International Journal Of Poultry Science
Effect of Dietary Supplementation with Different Levels of Arginine on Some Blood Traits of Laying Hens
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This experiment was carried out at the Field of Poultry, Department of Animal Resources, College of Agriculture, University of Baghdad, during the period from 1/5/2011 until 5/7/2011 to study the effect of adding arginine to laying hens diet on certain blood traits. A total of 100 Brown Lohmann laying hen chickens, 38 weeks of age, were randomly distributed into four treatment groups, with 25 hens for each treatment. Treatment groups were: T1: bird-fed diet with no additional arginine (control group); T2, T3, and T4: bird-fed diet supplemented with 0.4, 0.7, and 0.9%, respectively. Therefore, the total amounts of arginine in the four treatments (T1, T2, T3, and T4) become 1.1, 1.5, 1.8, and 2.0%, respectively. Results of this experiment rev

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Publication Date
Sat Jun 01 2024
Journal Name
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Study of The Effect of Concentration on The Efficiency of The Sensitive N749-TiO2 Solar Cell
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In this research, we studied the effect of concentration carriers on the efficiency of the N749-TiO2 heterogeneous solar cell based on quantum electron transfer theory using a donor-acceptor scenario. The photoelectric properties of the N749-TiO2 interfaces in dye sensitized solar cells DSSCs are calculated using the J-V curves. For the 〖(CH_3)〗_3 COH solvent, the N749-TiO2 heterogeneous solar cell shows that the concentration carrier together with the strength coupling are the main factors affecting the current density, fill factor and efficiency. The current density and current increase as the concentration increases and the strength coupling increases as the N749-TiO2 heterogeneous in solar cell. However, the efficiency is more sens

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Publication Date
Fri Nov 01 2013
Journal Name
International Journal Of Advanced Research
The effects of alkaloid extracted of Solanum nigrum leaves on the biological performance of Dialerodus citri
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