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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 Mar 01 2009
Journal Name
Baghdad Science Journal
Effect Of Chlorothalonil On Some Cytogenetic Parameters Of Human Peripheral Blood Lymphocytes
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The study aimed to investigate the effect of fungicides chlorothalonil at different concentrations ( 0.1 , 0.5 , 5 , 25 , 50 ) × 10 - 5 M on some cytogenetic parameters of human peripheral blood lymphocytes . The genotoxicity parameters were estimated by the number of chromosomal aberrations (CAs) and their types and by estimating the induced micronuclei (Mn) . Cytotoxic effect recorded by estimating the mitotic index (MI) . Results revealed that the fungicide increased the CAs in dose – response pattern with positive correlation coefficient ( r = + 0.964) , there was a significant differences among the concentrations (P<0.01) . The major CAs records chromosomal breakage at concentrations. 0.5 , 5 , 25 , and 50 , while the lowest concen

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Publication Date
Sat Feb 07 2026
Journal Name
Al-adab Journal
The Sense of Freedom in Kate's Chopin's The Story of an Hour
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Tue Jan 01 2019
Journal Name
Technologies And Materials For Renewable Energy, Environment And Sustainability: Tmrees19gr
Theoretical study for the calculation of some attenuation parameters of polymeric composites
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Publication Date
Wed Dec 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Comparison of Immunohistochemical Expression of DNMT3B among Oral, Laryngeal and Skin SCC
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Background: Recently epigenetic alterations have received increased attention because of theirimportant role in the process of tumerigenesis. It has been found that more than half of genetic changes were epigenetic. Epigenetic alterations are catalyzed by DNMTs enzymes. Increased knowledge about this molecular event may achieve progress in the war against cancer. The aim of this study was to evaluate and compare the expression of DNMT3B among oral, laryngeal and skin SCC. Materials and Methods: This study was performed on (120) formalin-fixed, paraffin-embedded blocks, histopathologically diagnosed as oral, laryngeal and skin SCC). Immunohistochemical staining of DNMT3B antibody was performed on each case of this study. Results: The immunoh

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Publication Date
Sun Jan 01 2023
Journal Name
International Journal Of Research In Social Sciences &amp; Humanities
The Role of Labor Relations in Reducing the Cases of Job Withdrawal
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he current research aims to analyze the relationship and the level of influence of labor relations in reducing the cases of job withdrawal in private colleges in Baghdad. (265) individuals from department heads, university professors, and teaching staff in (7) private colleges located in the capital, Baghdad, and based on the Stephen Thompson equation for small samples, the sample size was determined by (157) teachers, and the questionnaire was adopted as a main tool for collecting data and information After ensuring the validity and reliability of its contents, and to test the relationship of influence, correlation and interaction between the research variables, two main hypotheses were formulated from which (5) sub-hypotheses eman

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Publication Date
Sun Mar 06 2011
Journal Name
Baghdad Science Journal
The effect of additives metal on the D.C conductivity of epoxy resin
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The present studies are focused on the modification of the properties of epoxy resin with different additives namely aluminum, copper by preparing of composites systems with percentage (20%, 40% and 50%) of the above additives. The experimental results show that the D.C of conductivity on wt% filler content at ( 293-413 ) K electrical conductivity of all above composites increased with temperature for composites with filler contact and find the excellent electrical conductivity of copper and lie between (2.6*10-10 - 2.1*10-10)?.cm . The activation energy of the electrical conductivity is determined and found to decrease with increasing the filler concentration.

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Publication Date
Mon Mar 27 2023
Journal Name
Aip Conference Proceedings
Stability of Kongele earth dam against rapid drawdown of water from reservoir
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ABSTRACT In dam construction stages when an earth embankment has retained a reservoir with constant water surface elevation for a long time, seepage conditions within the embankment will be reach a steady state. If it is necessary to drain the reservoir quickly, the pore-water pressures in the embankment may remain relatively high while the stabling effect of the reservoir's weight along the upstream (U/S) side for the embankment has removed. This process is referring to as "Rapid Drawdown" and may be cause instability in the upstream (U/S) face of the embankment. Kongele dam is one of the proposed earth dams to be implement within the current plan in Iraq. The authors study pore water pressure and the effect of rapid drawdown for the dam d

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Publication Date
Fri Oct 01 2010
Journal Name
2010 Ieee Symposium On Industrial Electronics And Applications (isiea)
Effectiveness of the cumulative vs. normal mode of operation for combinatorial testing
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Publication Date
Fri Jan 01 2021
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The impact of quality costs in improving the quality of health services
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Improving the quality of health services in the health sector is an important and necessary matter that must be taken care of and improved, and this study seeks to demonstrate the role of quality costs in improving the quality of health services and achieving a high level of quality to satisfy the beneficiaries and to provide health services of good quality, and the research concluded that the main point of service provision Good health is the costs of prevention and evaluation (costs of quality conformity) and attention to it, and that technical competition contributes greatly to the development of the level of quality, as well as the use of health and medical staff with competent expertise, and that the costs of internal failure and th

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Publication Date
Tue Dec 20 2022
Journal Name
Iraqi Journal Of Biotechnology
Green Method Synthesis of Silver Nanoparticles Using Leaves Extracts of Rosmarinus officinalis
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The silver nanoparticles synthesized have to be handled by humans and must be available at cheaper rates for their effective utilization; thus, there is a need for an environmentally and economically feasible way to synthesize these nanoparticles. Therefore, this study aimed to synthesis of silver nanoparticles using phenolic compounds extracted from Rosmarinus officinalis. The maceration method and Soxhlet apparatus were used to prepare aqueous and methanolic Rosmarinus officinalis leaves extracts respectively, Furthermore, Rosmarinus officinalis silver nanoparticles (RAgNPs) were prepared from the aqueous and methanolic leaves extract of this plant and diagnosed using the ultraviolet (UV) spectroscopy, scanning electron microscopy (SEM),

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