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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
Tue Dec 01 2020
Journal Name
Baghdad Science Journal
Prevalence of Diabetes Mellitus in Hepatitis C Patients in Wazirabad Tehsil of Gujranwala District of Pakistan: hepatitis C in Diabetic patients
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Hepatitis, a condition of liver’s inflammation that can be self-limiting or, in certain chances, it may lead to liver cancer, fibrosis or cirrhosis. Hepatitis viruses mainly cause hepatitis in the world. People with hepatitis C have predominant chances to develop diabetes as HCV virus participates in causing type 2 diabetes. HCV virus causes pathogenesis in two ways: it either directly destroys the β cells of pancreas or contributes to the specific autoimmunity of β cells. The present cross sectional study was done in Wazirabad Tahsil of Gujranwala District to analyze the percentage of patients suffering from hepatitis C who had the risk of diabetes mellitus. For this research work, demographic information and data about any other me

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Fri Oct 30 2020
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Journal Of Economics And Administrative Sciences
The role of internal marketing in achieving customer satisfaction An exploratory study of a sample of private bank managers in Baghdad
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This study examined the effect of elements of internal marketing activities on customer satisfaction through an exploratory study of banking services in the city of Baghdad, if the research problem crystallized by asking a group of questions, the most important (is there a correlation and impact between the dimensions of internal marketing and customer satisfaction, this study aims to determine The effect of internal communication, training and internal market research on customer satisfaction, represented by the quality of service, loyalty and market share, and embodied the objective of this study to identify the level of availability of internal marketing activities and programs in the research banks, data were collected using

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Sat Sep 01 2018
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
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Sat Oct 01 2016
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Practice of Continuous Auditing in accordance with Technology Acceptance Model: An analytical study of a sample of the Iraqi auditing Offices
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This paper discusses the essence of the developmental process in auditing firms and offices at the world today. This process is focused on how to adopt the audit concepts which is based on Information and Communication Technology (ICT), including the Continuous Auditing (CA) in particular. The purpose of this paper is to design a practical model for the adoption of CA and its requirements according to the Technology Acceptance Model (TAM). This model will serve as a road map for manage the change and development in the Iraqi auditing firms and offices. The paper uses the analytical approach in reaching to the target results. We design the logical and systematic relations between the nine variable

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Publication Date
Mon Dec 23 2019
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The Effect Of Employing The Strategy Of The TalkativeGroups On The Achievement And Attitudes Of ChemistryFor Fifth Grade Students Applied Scienc
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The study aimed to reveal the impact of employing the strategy of the talk-ative groups on the achievement and academic tendencies of chemistry forstudents of the fifth grade of applied science for the academic year (2018 -2019), and to achieve this goal the researcher used the experimental methodon the sample of the study consisting of (50) students, prepared achievementtest falls Under (60) paragraphs, and the scale of tendencies for chemistryfalls under (30) paragraphs, and after the researcher completed the researchexperiment according to what was planned:The superiority of the experimental group studied according to the strate-gy of the talkative groups was found in the post-application of the test ofachievement and attitudes of chemis

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Publication Date
Fri Feb 09 2024
Journal Name
Eximia
The reality of the moral climate and its relationship to the decision-making of boxing referees from the standpoint of coaches
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The purpose of this paper is to identifying the relationship between the moral climate and the decision-making of boxing referees from the standpoint of the coaches, and the research problem lies through the work of the researchers in training and managing the teams. It was noted that the role of the referees is one of the most important roles played by the workers to achieve the objectives of the federation, and that the moral climate that prevails among the administrative body the union and the referees on the one hand and between the referees and coaches on the other hand are among the factors of the success of everyone’s work and the survival and strengthening of confidence in their work and thus the continuity of success and

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Publication Date
Tue Dec 29 2020
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The Impact of Electronic Payment systems on the Profitability of Banks: An applied research on a sample of Iraqi commercial banks
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Due to technological developments in the Iraqi banking sector, which is the use of electronic payment systems within the banking infrastructure. This has led to speed and accuracy in the completion of transactions, reduced costs, increased revenues and efficiency. This research examines the challenges and risks facing the Iraqi banking sector as a result of its use of electronic payment systems. And show its impact on the profitability of commercial banks. The research was based on the main hypothesis that there is a statistically significant moral impact relationship between electronic payment systems and the profitability of banks. Iraqi commercial banks were chosen as a research community, All Iraqi commercial banks that parti

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Publication Date
Sat Sep 01 2018
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Difficulties of scientific research in the financial and administrative fieldaccording to the quality standardsfrom the point of view of the teachers
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The research aims to identify the most important difficulties facing the scientific research in the technical university in the financial, organizational and administrative according to the quality standards according to the paragraphs studied in the questionnaire questionnaire prepared for this purpose, including the research community on the Central Technical University, which includes several technical colleges and technical institutes were selected A sample of the researchers in the Institute of Technical Management where the number of training was 78 teachers took a random sample of researchers amounted to 40% of the questionnaire, and after the collection and classification of data were used statistical means, including the mean ar

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Publication Date
Thu Jun 27 2019
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
A SURVEY OF WEEVILS (COLEOPTERA, CURCULIONOIDEA) FROM SOME LOCALITES OF KURDISTAN REGION- IRAQ, WITH NEW RECORDS TO THE ENTOMOFAUNA OF IRAQ
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This work is the first study of the Curculionoidea fauna from Kurdistan region of Iraq, based on the intensive survey in different localities of Kurdistan from March 2016 to November 2017. In total, 41 species belonging to 28 genera, 21 tribes and 3 families were collected and identified, including 25 species newly recorded for the Iraqi fauna.

 

General distribution, collecting localities and methods, with plant association data for each species are given.

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Publication Date
Fri Jan 01 2021
Journal Name
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The importance of using the World Wide Web (the Internet) for professors of Arabic Language Department at the University of Baghdad‏
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