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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 Jan 01 2023
Journal Name
International Journal Of Research In Social Sciences & Humanities
The House of Bernarda Alba: The Image of Repression and Female Rebellion Through the Character of Adela
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In the present work, the image and representation of Adela, the youngest daughter of the family of the Casa de Bernarda Alba, one of the most popular works of the Spanish author Federico García Lorca (1898-1936), will be analyzed. In this work, there are different themes, but what concerns us is to show the repression, oppression and rebellion of this character in a context of customs of the 1920s in Spain. They are revealing elements in that period in which women were relegated to the background, despite the fact that a feminist movement had already begun in Spain. By studying Adela, we seek to see how a single woman confronts her family and the society that surrounds her to fight for freedom, although its end is finally linked to

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Publication Date
Tue Jun 15 2021
Journal Name
Al-academy
Forms of post-modernism in performance of Iraqi theatre "dream of Baghdad exam": عمار عبد سلمان محمد
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  The effects of postmodernism on theatrical form was managed by the director (Anas Abdul Samad) to be employed in the Iraqi play (Dream in Baghdad) and the researcher sought to study this problem and divided it into four chapters dealt with in the first chapter the problem of research and its need, the importance of research, As well as the definition of terminology, either Chapter II theoretical framework divided by the researcher to the first two is the postmodernism in the theater is the most prominent reference references and the second most important postmodern applications in the world play and then the researcher concluded the second chapter of the most important indicators. In the third chapter, the researcher identified th

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Publication Date
Fri Apr 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
Foreign Trade of Iraq Between the imperatives of economic diversification And the challenges of joining the (WTO)
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         Interested in this research shed light on the reality of foreign trade to Iraq Who suffers from a marked deterioration due to poor economic diversification of the country And increase the degree of economic exposure   , Which creates a state of extreme caution towards the question of accession to the (WTO)   , As controls Iraq's foreign trade commodity  , a president of one oil As well as the contribution of this item  , and by a large formation in GDP   , And that such a large and dangerous decline in the degree of economic diversification will create negative effects On overall economic activity components&

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Publication Date
Thu Apr 30 2020
Journal Name
Journal Of Economics And Administrative Sciences
The impact of the of Six Sigma to improve the performance of dentists in albaladeat specialized Dental
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The research aims at introducing the principles of six sigma and if it had any effect of the dimensions of six sigma to improve the performance of the dentists and the availability of an appropriate environment in the center Specialist respondent to the application of six sigma principles and how to adopt Specialized Center under the dimensions of the six sigma and if there informed enough with the management methodology six sigma, and if you can adopt six sigma as one of the entrances to reduce medical errors. So  Search creating six sigma five dimensions and are (the commitment and support of senior management, the focus  on the patient, continuous improvement, training and civil, and infrastructure) as a variable int

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Publication Date
Sun Jan 01 2017
Journal Name
Transportation Research Procedia
The importance of intelligent transport systems in the preservation of the environment and reduction of harmful gases
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Publication Date
Sat Oct 01 2022
Journal Name
Baghdad Science Journal
Toxicity of Nanomulsion of Castor Oil on the Fourth larval stage of Culex quinquefsciatus under Laboratory Conditions
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Mosquitoes like Culex quinquefasciatus are the primary vector that transmits many causes of diseases such as filariasis, Japanese encephalitis, and West Nile virus, in many countries around the world. The development in the scientific fields, such as nanotechnology, leads to use this technique in control programs of insects including mosquitoes through the use of green synthesis of nanoemulsions based on plant products such as castor oil.  Castor oil nanoemulsion was formulated in various ratios comprising of castor oil, ethanol, tween 80, and deionized water by ultrasonication. Thermodynamic assay improved that the formula of (10 ml) of castor oil, ethanol (5ml), tween 80 (14 ml) and deionized water (71ml)   was mor

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Publication Date
Tue Jan 01 2019
Journal Name
Journal Of Global Pharma Technology
Analysis of fatty acids of liver in the embryo and adult of domesticated chicken gallus gallus domesticus
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The fatty acids in the embryo's liver at ages (7, 11, 14 and 19) days incubation, small chicken aged (14) days after hatching and adult were analyzed, and found (5) fatty acids, the highest concentration of fatty acid in the adult of domesticated chicken and lowest concentration in small chicken age (14) days after hatching. Statistically, there were high significant differences at the probability level (P≤0.001) between all ages together, and the highest concentrations of Oleic acid (C18:1) and Linoleic acid (C18:2) were in embryo age (7) days incubation, while in embryo age (11) days incubation Stearic acid (C18:0) and α-Linolenic acid (C18:3) were higher concentration and Palmitic acid (C16:0) was the highest concentration in the adul

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Publication Date
Wed Sep 29 2021
Journal Name
College Of Islamic Sciences
Reading in the thought of Imam Ali The philosophy of dialogue and the unity of the nation,
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This study is taken from the doctoral thesis that I prepared in the year 2000 at the University of Bordeaux in France under the title “ Ali bin Abi Talib Imam and Calif “. This thesis was prepared as a continuation of what the French orientalism Louis Massignon wrote about Islam and his student Henry Corbin, who introduced Europeans to Shiism. This study represents the philosophy of dialogue and the unity of the Islamic Emma as one of the most important methods used by Imam Ali.

Imam Ali established the most beautiful, creative, and most complete rules of human dialogue that preserve the unity of the nation’s fabric and preserves human dignity. Imam Ali referred to basic principles foundations to reach this goals, including

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Publication Date
Wed Oct 17 2018
Journal Name
Journal Of Economics And Administrative Sciences
The requirements of agricultural investment in Iraq in light of his accession Of the World Trade Organization
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Abstract              
          Agricultural investment is one of the main requirements in most economies of the world for its importance in the development of the agricultural sector through the agricultural and technological infrastructure and agricultural research, as well as its impact on most economic, social and service activities, especially if managed and employed scientifically, which generates income and productive capacities and services and new commodities, Unemployed as agricultural investments in Iraq fell significantly after 2003 due to economic, political, social

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Prevalence of B-Thalassemia Carriers Among a Cohort of University Students in Hawler Province of Iraqi Kurdistan
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         A representative sample of a thousand volunteer university students was screened for evidence of thalassemia minor.Complete blood counts using automated blood cell analysers and blood smears were examined. Patients having anemia, abnormal red cell indices or morphological features of thalassemia minor like hypochromia, microcytosis, target cells erythrocytosis and family history of thalassemia were then investigated for determination of  HbA2 & HbF levels. Estimation of hemoglobin A2 was performed by micro-column chromatography while HbF was done using alkali denaturation. Seventy seven out of the thousand samples tested positive for thalassemia minor. They all showed a hemoglobin A

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