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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 Feb 28 2021
Journal Name
Journal Of Electrochemical Science And Technology
Simultaneous Removal of Cadmium and Copper from a Binary Solution by Cathodic Deposition Using a Spiral-Wound Woven Wire Meshes Packed Bed Rotating Cylinder Electrode
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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Mixed Ligand Complexes of quinoline-2-carboxylic acid and 4,4/-dimethyl-2,2/-bipyridyl with V(IV),Cr(III), Rh(III), Cd(II) and Pt(IV)
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A new mixed ligand complexes were prepared by reaction of quinoline -2-carboxylic acid (L1) and 4,4?dimethyl-2,2?-bipyridyl (L2) with V(IV),Cr(III), Rh(III), Cd(II) and Pt(IV) ions. These complexes were isolated and characterized by (FT-IR) and (UV-Vis) spectroscopy, elemental analysis, flame atomic absorption technique, thermogravimetric analysis, in addition to magnetic susceptibility and conductivity measurements. Most complexes were mononuclear and with octahedral geometry, except Cd (II) with tetrahedral geometry, and V (IV) with square pyramidal geometry. A theoretical treatment of the ligands and the prepared complexes in gas phase was done using two programs Hyperchem.8 and Gaussian program (GaussView Currently Available Versions (

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Publication Date
Sat Apr 20 2024
Journal Name
International Journal Of Disabilities Sports & Health Sciences
Psychological Toughness and its Relationship to Some Coordination, Physical Abilities and Accuracy of Some Basic Skills Performance Among the Iraqi Junior National Handball Team Players
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The aim of the research is to identify psychological toughness and its relationship to some coordination, physical abilities and accuracy of some basic performance skills among the players of the Iraqi junior national handball team players. The hypothesis is the existence of a correlation between psychological toughness, coordination, physical abilities, and the accuracy of some basic skills performance among the players of the Iraqi junior national handball team players. The descriptive approach in the style of correlational relations used to suit the research problem, as the community was determined by (18) players for the Iraqi junior national handball team players, while the sample was (14) players, and the samp

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Thu Oct 01 2020
Journal Name
Biochemical And Cellular Archives
Study on the effect of methotraxate drug on Retinol-Binding Protein 4 (RBP4), nesfatin and some trace elements in Iraqi male patients with rheumatoid arthritis
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Methotrexate (MTX) is one of the most effective medications to treat rheumatoid arthritis (RA).Aserum of 60 Iraqi male patients suffering from RA as (G1) was newly diagnosis and the same patient in G1 after taking MTX as G2 and 40 Iraqi male healthy control as G3. Nesfatin-1 (Nf-1) is belong to the adipokine family withpleiotropic effect. Nf-1 has been found in different tissues, including stomach, pancreas, bone cells, cartilage and heart. Retinol binding protein (RBP4) was known as transpoter of retinol from its storage sites in the liver to the extrahepatic tissues. Moreover, RBP4 acts as adipokine and contributes in the pathophsyology of prototypic inflammatory disease, rheumatoid arthritis (RA). The results showed a significant increas

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Publication Date
Tue Mar 18 2025
Journal Name
Journal Of Baghdad College Of Dentistry
The relationship among bite force with facial dimensions and dental arches widths in a sample of Iraqi adults with Class I skeletal and dental relations
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Background: This study aimed to determine whether there is a relationship among the bite force with facial dimensions and dental arches in a sample of Iraqi adults with Class I skeletal and dental relations. Materials and methods: Forty dental students (20 males and 20 females) were selected under certain criteria. For those individuals, dental impressions, frontal facial photographs and maximum bite force at molar and incisor regions were taken. The dental arches widths and facial dimensions were measured using the AutoCAD program 2007, while the bite force was determined using special device. Descriptive statistics for the measured variables were performed and gender difference was determined using independent sample t-test, while the rel

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Publication Date
Sat Jan 01 2022
Journal Name
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The Molecular Identification of Pathogenic E. coli Isolated from Raw Cow Milk and Assessment Their Anti-susceptibility to Medical Plants at Al-Najaf city/ Iraq
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Background: Toxin-producing Shiga Escherichia coli has been identified as a new foodborne pathogen that poses a significant health risk to humans. Shiga toxin-producing Escherichia coli can be found in raw cow milk and its derivatives. A small number of Escherichia coli strains that produce shiga toxin are pathogenic. Aim of study: The study aimed to see if there were any virulence genes in 50 milk samples that were typical of Entero-haemorrhagic E. coli and evaluate the Myrtus communis effects on these bacteria. Materials and Method: Milk samples were used to isolate E. coli bacteria (n= 27), biochemically analyzed, and genetically screened for virulence genes using a multiplex (PCR). The hydro-alcoholic extraction of Myrtus communis leave

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Publication Date
Sun Sep 07 2014
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Baghdad Science Journal
Comparison the effectiveness of using a magnetic field to control theColi phages isolated from rivulet water with water-treatment using magnetic field added iron filings
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The present study aimed to use the magnetic field and nanotechnology in the field of water purification, which slots offering high efficiency to the possibility of removing biological contaminants such as viruses and bacteria rather than the use of chemical and physical transactions such as chlorine and bromine, and ultraviolet light and boiling and sedimentation and distillation, ozone and others that have a direct negative impact on human safety and the environment. Where they were investigating the presence in water samples under study Coli phages using Single agar layer method and then treated samples positive for phages to three types of magnetic field fixed as follows (North Pole - South Pole - Bipolar) and compare the re

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Thu Mar 10 2011
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ESTIMATION OF GENE ACTION AND GENETIC PARAMETERS FOR SOME VEGETATIVE AND FLOWERY GROWTH CHARACTERS IN SUMMER SQUASH (Cucurbita pepo L.) BY USING MEAN GENERATION ANALYSIS
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An experiment was carried out in the vegetables field of Horticulture Department / College of Agriculture / Baghdad University , for the three seasons : spring and Autumn of 2005 , and spring of 2007 , to study the type of gene action in some traits of vegetative and flowery growth in summer squash crosses (4 x 3 = cross 1 , 3 x 7 = cross 2 , 3 x 4 = cross 3 , 3 x 5 = cross 4 , 5 x 1 = cross 5 , 5 x 2 = cross 6). The study followed generation mean analysis method which included to each cross (P1 , P2 , F1 , F2 , Bc1P1 , Bc1P2) , and those populations obtained by hybridization during the first and second seasons. Experimental comparison was performed in the second (Two crosses only) and third seasons , (four crosses) by using RCBD with three

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Tue Mar 18 2025
Journal Name
Revista Iberoamericana De Psicología Del Ejercicio Y El Deporte, Issn 1886-8576, Vol. 18, Nº. 1, 2023, Págs. 19-29
Constructing A Measure of Psychological Disability and Its Relationship to Some Basic Skills and Fixed Playing Situations for Youth Football Players Under (19) Years Old
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Autorías: Muwafaq Obayes Khudhair, Sanaa Rabeea Abed, Hayder Talib Jasim. Localización: Revista iberoamericana de psicología del ejercicio y el deporte. Nº. 1, 2023. Artículo de Revista en Dialnet.

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Publication Date
Wed Dec 01 2021
Journal Name
Journal Of Physics: Conference Series
The effect of left ventricle ischemia severity on cardiac performance appeared on ejection fraction using radioactive TC <sup>99m</sup> MIBI in comparison with echocardiography
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