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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
Mon Aug 01 2011
Journal Name
Journal Of Engineering
RELIABILITY ANALYSIS OF THE SEISMIC STABILITY OF EMBANKMENTS REINFORCED WITH STONE COLUMNS
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Geotechnical engineers have always been concerned with the stabilization of slopes. For this purpose,
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Fri Jul 21 2023
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The Effect Of Curing Types On Compressive Strength Of High Performance Concrete
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The present investigation considers the effect of curing temperatures (30, 40, and 50˚C) and curing compound method on compressive strength development of high performance concrete, and compares the results with concrete cured at standard conditions and curing temperature (21˚C). The experimental results showed that at early ages, the rate of strength development at high curing temperature is greater than at lower curing temperature, the maximum increasing percentage in compressive strength is 10.83% at 50C˚ compared with 21C˚ in 7days curing age. However, at later ages, the strength achieved at higher curing temperature has been less, and the maximum percentage of reduction has been 5.70% at curing temperature 50C˚ compared with 21

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Sun Sep 07 2014
Journal Name
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Factors Influence on the yield of Bacterial Cellulose of Kombucha (Khubdat Humza)
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Kombucha(Khubdat Humza) is composed of yeast and acetic acid bacteria especially, Acetobacter xylinum which forms a cellulose pellicle on tea broth. Kombucha(Khubdat Humza) produces bacterial cellulose pellicles, with unique purity and fine structure. It can be used in many forms, such as an emulsifier, stabilizer, dispersing agent, thickener and gelling agent but these are generally subsidiary to its most important use of holding on to water. Recently, bacterial cellulose is used in many special applications such as a scaffold for tissue engineering of cartilages and blood vessels, also for artificial skin for temporary covering of wounds, as well as its used in the clothing industry. The yield of cellulose produced were investiga

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Sat Apr 01 2023
Journal Name
Iop Conference Series: Earth And Environmental Science
Detection of Mineral and Microbial Contaminants in some Types of Imported Meat
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Abstract<p>The main target of the current study is to investigate the microbial content and mineral contaminants of the imported meat available in the city of Baghdad and to ensure that it is free from harmful bacteria, safe and it compliances with the Iraqi standard specifications. Some trace mineral elements such as (Iron, Copper, Lead, and Cadmium) were also estimated, where 10 brands of these meats were collected. Bacteriological tests were carried out which included (total bacterial count, <italic>Staphylococcus</italic> bacteria, <italic>Salmonella</italic> bacteria). The results showed highest number of total bacterial count 13×10<sup>5</sup> CFU/g in F8 bra</p> ... Show More
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Publication Date
Mon Mar 15 2021
Journal Name
Route Educational & Social Science Journal
THE EFFECTIVENESS OF POLITICAL IDEOLOGY IN THE DESIGNS OF INTERNATIONAL MAGAZINE COVERS
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Publication Date
Thu Feb 19 2026
Journal Name
Revista Iberoamericana De Psicología Del Ejercicio Y El Deporte, Issn 1886-8576, Vol. 17, Nº. 5, 2022, Págs. 269-271
The effect of a suggested rehabilitation curriculum in the treatment of partial rupture of the gluteal muscles and strengthening the working muscles of the pelvic joint in football players
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Autorías: Imad Kadhim Khlaif, Israa Gameel Hussein, Talib Faissal Shnawa. Localización: Revista iberoamericana de psicología del ejercicio y el deporte. Nº. 5, 2022. Artículo de Revista en Dialnet.

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Publication Date
Sun Sep 06 2015
Journal Name
Baghdad Science Journal
Preparation of Some Culture Media Locally from leaves and stems of Purslane plant (Portulaca oleracea oleracea L.) and Assessment of Their Efficiency Comparing with Culture Media of Oxoid Company
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Publication Date
Wed Sep 08 2021
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The effect of financial leverage on the market value of the shares of Iraqi commercial banks: An applied research in the Bank of Baghdad for the period (2010-2019)
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The aim of the research is to know the effect of financial leverage on the market value of the stock by applying it to a sample of private Iraqi commercial banks listed in the Iraqi Stock Exchange for the period (2010-2019) and to show the extent of that effect, based on the bank’s annual reports for the mentioned period through the use of financial leverage ratios represented b (Equity multiplier, cash balance ratio), its discussion, analysis, description, inferential description, and testing of research hypotheses,

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Publication Date
Sat Dec 28 2024
Journal Name
Journal Of Physical Education
Obstacles to achieving quality field application performance from the point of view of fourth-stage female students at the College of Physical Education and Sports Sciences, University of Baghdad
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Publication Date
Sat Dec 01 2018
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The Impact of the Application of Corporate Governance On the Financial Performance Evaluation in Banks: Applied Study- Sample of the Conventional and Islamic Banks in the Kingdom of Bahrain
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 The aim of this research is to identify the extent to which the Conventional and Islamic banks are committed to implement the requirements of the corporate governance in its financial reports. In addition to its commitment to transparency and clarity in dealing with the shareholders and stockholders to protect their interests and to determine the impact of the commitment of the corporate governance on assessing the financial performance of the conventional and Islamic banks that participate in Bahrain Stock Exchange.

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