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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 Sep 30 2004
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Iraqi Journal Of Chemical And Petroleum Engineering
Production of Formaldehyde by Catalytic Conversion of Methanol
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Fri Feb 01 2013
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Proceedings Of The Institution Of Civil Engineers - Ground Improvement
Treatment of collapse of gypseous soils by grouting
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Gypseous soil is a collapsible soil, which causes large deformations in buildings that are constructed on it. Various methods have been used to minimise this effect, such as replacing the gypseous soil or using soil stabilisation (grouting or soil improvement). This study was carried out on four types of gypseous soils that have different properties and various gypsum contents. The testing was carried out on remoulded samples to evaluate the compressibility of gypseous soil under different conditions. The samples were grouted with acrylate liquid. The relationships between the injection pressure and the radius of flow, between time of injection and radius of flow, and between time and quantity of acrylate liquid are investigated on

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Wed Dec 30 2020
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Journal Of Accounting And Financial Studies ( Jafs )
The effect of salary Domiciliation in the rate of return on assets (ROA): Applied research of a sample of Iraqi banks
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The research attempted to find an explanation and solution to a problem related to the fluctuation and decrease In the rate of return on assets for the research sample banks during the duration of the research, The search started from the hypothesis that, The effect of salary Domiciliation on the banking profitability of a sample of Iraqi banks participating in the salary settlement system for the period (2016-2019),The research used the descriptive historical approach, the quantitative analytical approach and the statistical approach. The research reached a set of conclusions, the most important of which is The effect of salary Domiciliation on banking profitability was achieved in three banks

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Sun Sep 01 2024
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Al-rafidain Journal Of Medical Sciences ( Issn 2789-3219 )
The Sensitivity of Immunohistochemical Expression of p53 as an Indicator of the Malignant Potential of Gastric Hyperplastic Polyps: A Retrospective Study
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Background: Hyperplastic polyps account for 30–93% of gastric polyps. Recently, there have been studies about the development of dysplasia in this type of polyp. Every cell in the body contains the p53 gene, which has anti-cancer properties. Objective: The sensitivity of immunohistochemical expression of p53 is evaluated among gastric hyperplastic polyps with and without dysplasia and gastric adenomatous polyps to know its usefulness as a diagnostic marker. Methods: A retrospective cross-sectional study was done on fifty formalin-fixed paraffin-embedded blocks of gastric polyps (44 hyperplastic polyps without dysplasia, 3 hyperplastic polyps with dysplasia, and 3 adenomas). Cases were collected from the archives of the pathology d

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Sun Jun 01 2014
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Journal Of Economics And Administrative Sciences
the role of senior management commitment to total quality in the implementation of knowledge management processes_Asurvey of asample of civil colleges
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Occupies total quality management applications play a key role in the development of institutions of higher education performance and achieve its strategic objectives through the commitment of senior management and their employees to continuous improvement of the quality of performance in the various areas of work, and can be integrated knowledge management processes, which means identifying information of value and how to take advantage. The data were collected using the style of the questionnaire for the purpose of analyzing their results on a sample composed of 83 member of the administrative leadership in colleges as representing the decision-making centers in those colleges . 

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Publication Date
Thu Dec 01 2011
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application of business managment in the field of football with studuy of the case of spanish club (Real Madrid) و (Barcelona
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Football has progressed from being a ritual and a celebration to become an amateur sport, a professional sport, and now, increasingly, a commercial sport. In the analysis of football business model, the systemic approach should be adopted. If sport is regarded as one of the business sectors, then the application of business system methodology can be fully justified. The interest to create strong football business system calls for the search of the ways of popularizing football business model and boosting the economic potential of its participants. In the research literature tend to ignore the business processes within the sports business. Besides, the systemic approach in football business is usually limited to p

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Publication Date
Mon Feb 04 2019
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Journal Of The College Of Education For Women
Selected lssues Of the Imams Of Imam AL- Bazzai in the Book of Prayer from his Book of Fatwas AL- Bazaziyyah
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The research included four topics: the definition of Imam al-Bazzazi, his scientific life, his sheikhs, his students, his writings, his death, and selected issues of his weight in the book of prayer. The Imam al-Bazazi is the son of Muhammad ibnShihabibn Yusuf. He is known as al-Khardizi al-Khawarizmi. The author did not adopt the definitions of language and terminology, and rarely mention the legal evidence adopted by the scholars in their opinions, and only to mention the views only, and the author, may God have mercy on him in his book on the sources of m The Prophet (peace and blessings of Allaah be upon him) said: "The Prophet (peace and blessings of Allaah be upon him) And fall down the order, the third issue, which is to leave the

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Publication Date
Wed Jul 01 2015
Journal Name
Journal Of Educational And Psychological Researches
Reality and constraints of the use of computers in public schools in the governorate of Ma'an From the standpoint of teachers
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 This study aims to recognize the process of using computer in    publicschools in Ma`an governorate in terms of hardware, capabilities, and teachers usage. It also aims to identify the most important obstacles those schools face from a teachers perspective.

            The study sample consists of (150) teachers from different disciplines. The researcher prepared two questionnaires related to the research pivotal, then presented to a group of arbitrators to be used in this final form. The data was analyzed statistically and the study concluded that there is a shortage in the computer services provided to teachers, and there is a w

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Publication Date
Mon Feb 01 2021
Journal Name
Indian Journal Of Ecology
Effect of sedimentary source on the properties of sphericity and roundness of feldspar minerals in some soils of the alluvial plain
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This study was conducted on the effect of the sedimentary source (the sediments coming from both the Iraqi-Iranian borderline and the Tigris river) on the optical and textural features, especially sphericity and roundness of feldspar minerals (potassium and plagioclase types) in soils of the southern part of the alluvial plain. Eight pedons were selected to represent the study area, five of them represented sediments coming from the borderline, which included pedons of (Badra, Taj Al-Din, Al-Shihabi, Jassan, and Galati), while two of them represent the sediments of the Tigris River (Essaouira, Al-Dabouni), the pedon of Ali Al-Gharbi was represented the mixing area of sediments of all the floods coming from the borderline and the sediments o

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Wed Aug 27 2025
Journal Name
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Objective trends of university theses and dissertations of the College of Political Science at the University of Baghdad: an analytical study
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The research sought to identify the objective trends of postgraduate students at the College of Political Science - University of Baghdad for the period from 2000-2012 through the objective trends of university theses and dissertations and what are the most and least studied topics, with a re-adjustment of previously studied topics towards topics that serve issues of concern to society and avoiding topics that have been studied a lot to avoid repetition. The research came out with the following results, the most prominent of which are: The total number of what was accomplished in this college is 401 theses and dissertations, and the dissertations had the largest share of them, as their percentage reached 69%, with 275 theses compared to 126

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