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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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Thu Apr 30 2020
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The Effect of organizational stress on the Performance of professor at the Faculty of Economics and Commercial Sciences / University of Djelfa / Algeria
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The present study aims at identifying the effect of organizational pressure with its aspects (management, work team, nature and conditions of work, external environment) on job performance in all its dimensions (commitment and effort made, capabilities and the rapidity of performance, motivation and job satisfaction, work environment) for the university teacher at the Faculty of Economics, Commercial and Management Sciences at the University of Djelfa, Algeria.

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Sat Oct 11 2025
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Sun Oct 25 2020
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EFFECT OF EXERCISES USING DIFFERENT RESISTORS IN THE DEVELOPMENT OF THE SPECIAL STRENGTH OF THE ARMS AND THE COMPLETION OF JAVELIN FOR THE ATHLETES OF THE SCHOOL SPECIALIZED ATHLETICS
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Tue Oct 01 2019
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Publication Date
Wed Mar 30 2022
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The Role Of Smart Leadership Dimensions In Crisis Management- A study For Opinions Of Sample Of Administrative Leaderships In A number Of Humanities Colleges At The University Of Mosul
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Thu Dec 01 2016
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This study was to demonstrate the role-use planning scientific methods is disabled and little used in the planning and follow-up construction of vital projects in the province of Baghdad, including network planning methods, in order to find the optimal time to finish the project in light of the resources available and the budget set for it, in the current research has been used the most prominent network planning methods and two stylistic (CPM / PERT), was the application of the critical path method on standard-design school project (traditional) to draw Action Network according to confirmed times for the activities of the project and account his Crashing time , It was Pert technique applied to the project hemato

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Sat Jun 01 2013
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Requirements of stress tests model and the possibility to apply in Iraqi banks exploratory study of the views of a sample of staff in the central Bank of Iraq .
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This research attempt to explain the essential aspects of one important model in management of Bank risks , that is (stress testing) , which increase the concentrate on it resulting the negative affects of Global financial crisis that it accuar in 2008 to study the application possibilities in iraqian banks to enhancing the safety and financial soundness Becuase the classical tools  in Risk management don’t give clear image on Banks ability  in facing risks, hence the Basel committee on Banking supervision focusing in agreement of Basel 2,3 on stress testing when it doing the internal capital adequacy assessment process (ICAAP) .

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Publication Date
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Study the effect of the mixture aquatic extract of Peganum harmala seeds and Pericarp of Punica granutum on viability of protoscolices of Echinococcus granulosus in vitro and in vivo
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Publication Date
Sun Feb 03 2019
Journal Name
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The Attitudees toward aggresive behaviore for sample of college of education and college of science for womens student: The Attitudees toward aggresive behaviore for sample of college of education and college of science for womens student
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Abstract
The purposes of this study were to identifying the (attitudes of college of
education and college of science for womens in Baghdad university students
toward aggresive behaviore) and to determine the differences of student's
attitudes due to Specialization.
The study sample consists of (460) Female students.Aquestionave of
(59) items was desiged and distributed selected sample after established it's
validity and reliablity.The results indicated that the attitude of Baghdad
University For College of education and college of science students toward
aggresive behaviore were Negative.
The findings revealed that there were statistically significant differences
in the student's attitudes due to special

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