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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 Apr 30 2020
Journal Name
Journal Of Economics And Administrative Sciences
The Role of the values of accounting culture in maximizing financial performance - A field study in a sample of Iraqi banks
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The influence of culture on accounting systems and practices, including financial reports and accounting information through the values ​​identified by Gray and derived from social-cultural values, and the four accounting values ​​were derived from generally accepted accounting principles represented by (Conservatism, Uniformity, Secrecy, and Professionalism). Important and significant in maximizing financial performance, and measuring the extent of the role of these values ​​in improving financial performance through attention to the values ​​of accounting culture, this research

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Publication Date
Fri Mar 01 2013
Journal Name
Journal Of Economics And Administrative Sciences
The effect of Analysis of internal environment in the quality of health care service survey study at AL_Elwiya Maternity Teaching Hospital
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he current research aims at showing the correlation and effect of the internal environment analysis in the quality of health service in AL_Elwiya Maternity Teaching Hospital, researcher depended on the integral method in the "analytical descriptive method" for the study of the relation between the main variables and the sub-variables throughout data collection required by the theme of this study, a case study" in tackling the data and information related to the financial aspects of the internal environment.

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Publication Date
Thu Feb 06 2020
Journal Name
Political Sciences Journal
Self-immuniztion: integration of Russian strategic performance a study in the geopolitical orientation circles "of the stage of president putin"n
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In the period after the collapse of the Soviet Union in 1991, the Federal Republic of Russia witnessed a setback in the overall strategic performance of the country, as it went through a stage of performance flop between the orientation towards Europe in the era of President Boris Yelsen (1991-1999), or the change of direction towards Eurasia, as the Russian Federation managed After President Vladimir Putin assumed power in 2000, from rebuilding the same state and preserving national unity and social cohesion, as well as building a phased military doctrine that made clear moves in Russian strategic thought and future directions towards regions of eternal importance in Russian strategic perception Lack of a set of motivations based on it:

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Publication Date
Fri Dec 30 2011
Journal Name
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The Role of the Use of Low Molecular Weight Heparin in the Prevention of Deep Venous Thrombosis after Total Knee Arthroplasty
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Background A prospective clinical study was
performed to compare the efficacy of the use of lowmolecular-
weight heparin group (enoxparin group)
with control group in the prevention of deep-vein
thrombosis after total knee arthroplasty.
Aim of the study: to assess the prevalence of DVT
after total knee arthroplasty and evaluate the
importance of the use of low molecular weight
heparin in the prevention of this DVT.
Methods Thirty-three patients undergoing total
knee arthroplasty were randomly divided into two
groups. One group consisted of 12 patients who
received no prophylaxis with an anticoagulant (the
control group), other group consisted of 21 patients
who received the low-molecular-weight h

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Publication Date
Sun Aug 30 2020
Journal Name
Periodicals Of Engineering And Natural Sciences (pen)
Kernel estimation of returns of retirement funds of employers based on monetary earnings (subscriptions and compensation) via regression discontinuity in Iraq
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Regression Discontinuity (RD) means a study that exposes a definite group to the effect of a treatment. The uniqueness of this design lies in classifying the study population into two groups based on a specific threshold limit or regression point, and this point is determined in advance according to the terms of the study and its requirements. Thus , thinking was focused on finding a solution to the issue of workers retirement and trying to propose a scenario to attract the idea of granting an end-of-service reward to fill the gap ( discontinuity point) if it had not been granted. The regression discontinuity method has been used to study and to estimate the effect of the end -service reward on the cutoff of insured workers as well as t

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Publication Date
Fri Jun 20 1930
Journal Name
College Of Islamic Sciences
Evidence of the prophecy of Muhammad peace be upon him and established understanding In the letters of light: Study and analysis
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Provisions and controls on the disposal of public funds between Sharia and law
Research Summary
That money is the foundation of life and one of the most important reasons for the reconstruction of the land, and God is the owner
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They are charged with preserving it, since it is beneficial to them all, without anyone taking it
To himself, and the guardian is charged by God to protect this money and aggression
Because of its power, authority, various organs and public servants of the province
Upon him; Because the assault on public money by employees and others in the organs of the state
And exploitation of their jobs and this

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Publication Date
Mon Apr 01 2019
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EFFECT OF SOME GROWTH REGULATORS ON THE MULTIPLICATION AND STIMULATING THE PRODUCTION OF THE VOLATILE OIL OF ROSEMARY OFFICINALIS IN VITRO
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The experiment was conducted at the plant tissue culture laboratory of the Department of Horticulture and Garden Engineering College of Agricultural Engineering Sciences, University of Baghdad, in order to study the effect of some growth regulators on propagation an stimulation production of volatile oil compounds of rosemary plant Rosmarinus officinlis using two vegetative parts (apical and lateral buds). Factorial experiment was implemented in completely randomized design with twenty replications. The results indicated that culturing the apical meristem on the medium Murashige and Skoog (MS) media with 0.5 mg.l-1 (BA) with 0.1 mg.l-1 of NAA gave the highest response rate of 100%. As for the doubling stage, the levels of BAA and IAA (Indol

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Publication Date
Mon Feb 04 2019
Journal Name
Journal Of The College Of Education For Women
The Effect of the Translation of Poetic Poem Into an Artistic Picture in the Achievement of Retention Among Fifth Grade Students
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The purpose of this research is to identify
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Publication Date
Wed Sep 15 2021
Journal Name
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Design and implementation of a glove theater of cardboard materials for the students of the Kindergarten Department: قيس هاشم احمد النعيمي
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The current research aims to develop the skills of the kindergarten students in designing and implementing a theater for gauntlets made of cardboard materials. To study this, the researcher determined to build teaching plans for design and implementation skills according to (Kolb model).
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Publication Date
Thu Sep 15 2022
Journal Name
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The Impact of Mind and Informational Strategy on the ‎Achievement of the Second Intermediate Students in the Grammar ‎of Arabic Language
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The aim of the current research is to recognizing the impact of mind and informational strategy on the achievement with the second intermediate students in the grammar of arabic language, the researcher used a partial-set experimental design and intentionally selected a sample out of the second intermediate class from (AL- Markazya Intermediate school) in the district of Hilla, affiliated which belongs to General Directorate of Babylon Education in the year (2020-2021) for applying the experiment. The sample was composed of (50) students, (25) ones for each group, the experimental group and normal one. The researcher balanced between the two groups in various changes including: (the chronological age counted by months, the academic achie

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