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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 May 01 2018
Journal Name
Journal Of Physics: Conference Series
Synthesis, Characterization and Antibacterial Activity of 1,4-di[ aminomethylene carboxyl] phenylene (H2L) and its Complexes Co(II), Cu (II), Zn(II) and Cd (II)
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Publication Date
Tue Feb 14 2023
Journal Name
Journal Of Educational And Psychological Researches
Psychological Flow and its Association with Psychological Well-Being and Self –Management among a Sample of Fine Artists in Makkah Region Haneen Hussain Daggas
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Abstract

The research aims to examine the relationship between psychological flow, psychological well-being, and self-management among a sample of fine artists in the Makkah region and its governorates. The research also aims to examine the mean group differences in psychological flow, psychological well-being, and self-management due to demographic variables (sex and years of practicing arts). The sample consists of (110) male and female fine artists. The descriptive correlational approach was performed to collect the data by using the psychological flow scale developed by Payne et al (2011), which was translated by the researcher, the Oxford happiness questionnaire developed by Hills and Argyle (2002), it has t

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Publication Date
Mon Mar 13 2017
Journal Name
Journal Of Baghdad College Of Dentistry
Localization of Maxillary Impacted Canine Using Cone Beam Computed Tomography for Assessmentof Angulation, Distance From Occlusal Plane, Alveolar Width and Proximity to Adjacent Teeth
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ABSTRACT Backgrounds: Maxillary canine impaction is complicated and time consuming to treat, for being highly diverse in inclination and location; it may be a companied by root resorption of the neighboring teeth. CBCT has been used for its' diagnostic reliability in localization of impacted canine and revealing its' serious local complications. Objectives: Localization of maxillary impacted canine using cone beam computed tomography for assessment of angulation, distance from occlusal plane, alveolar width and proximity to adjacent teeth. Subjects and Methods: The study sample was 33 subjects 16 females and 17 males attended to Al-Wasitti general hospital in Baghdad city-Oral and maxillofacial radiology department for CBCT scan investigati

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Publication Date
Mon May 27 2019
Journal Name
Al-academy
Revival of the Heritage Using Porcelain Units Inspired by Traditional Sadou Decoration and Kufic Calligraphy in Fashion Design: تهاني ناصر العجاجي ---وجدان محمد الفليج
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The purpose of this research is to identify heritage and highlight its value by drawing on its decorative vocabulary and integrating it with the Arabic calligraphy to revive the heritage in a contemporary style, and to create decorative design units inspired by Sadou and Arabic calligraphy and to employ them in the modern fashion designs. The applied descriptive approach has been used in this research, and the research community is made of women in Riyadh area. The tools used in this research were the questionnaire and the observation. The most important results of the research are: the design of decorative units from the integration of Arabic calligraphy and the decorations of the Saduo, and the use of these units in the design of the o

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Publication Date
Thu Dec 29 2016
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Prevalence and Infection Rate of Three Gizzard Nematodes in the Mallard Anas Platyrhynchos L., 1758 Collected in Al-Diwaniya and Diyala Provinces , Central Iraq
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         Three nematodes : Amidostomum  acutum , Epomidiostomum uncinatum and Hadjelia truncata , were recovered from the gizzards of wintering mallard collected at two sites in central Iraq. A brief description of the parasites along with some notes on their infection rate, prevalence and discussion with the pertinent literature are provided.

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Publication Date
Sun Sep 06 2015
Journal Name
Baghdad Science Journal
Microwave Assisted Synthesis, Solution State, Spectral Studies and Theoretical Treatment of Pd(II) , Pt(IV) and Au(III) ions Complexes Containing 2-Benzamide Benzothiazole
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2-benzamide benzothiazole complexes of Pd(II) , Pt(IV) and Au(III) ions were prepared by microwave assisted radiation. The ligand and the complexes were isolated and characterized in solid state by using FT-IR, UV-Vis spectroscopy, flame atomic absorption, elemental analysis CHNS , magnetic susceptibility measurements , melting points and conductivity measurements. The nature of complexes in liquid state was studied by following the molar ratio method which gave results approximately identical to those obtained from isolated solid state; also, stability constant of the prepared complexes were studied and found that they were stable in molar ratio 1:1.The complexes have a sequar planner geometry except Pt(IV) complex has octahedral .

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Publication Date
Sun Dec 01 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Application of the excess cash margin model (ECM) to detect the Earning Management in the banking sector: Comparative study between commercial and Islamic banks
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The research draws its importance from identifying the methods of profit management in misleading the financial statements, which in turn is reflected in the decisions of the authorities that relied on these reports, and then the models that help in detecting those methods used by the auditors. Risks. The index (margin of excess cash) was used to detect profit management practices on a group of banks listed in the Iraqi market for securities and the number of (23) banks, including (12) commercial bank and (11) Islamic bank and the results were compared to commercial banks with Islamic banks.((The research started from the hypothesis that the use of the (excess cash margin) model in the banking sector reveals the management

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Publication Date
Thu Jun 06 2013
Journal Name
Advances In Physics Theories And Applications
Adsorption study of Symmetrical schiff base ligand 4,4 -[hydrazine -1,2- diylidenebis ( methan-1-yl-1-ylidene) bis ( 2-methoxyphenol)] on Granulated Initiated calcined Iraqi …
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Publication Date
Mon Jun 01 2009
Journal Name
Engineering And Technology Journal
Synthesis and study of the Novel tetradented ligand type N2O2 and its complexes with (Mn (II) ,Co (II) ,Ni (II) and Cu(II)) ions
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A new Schiff base ligand Bis-1,4-di[N-3-(2-hydroxy-1-amino)- acetophenonylidene] benzylidene [L] and its complexes with (Mn(II) ,Co(II) ,Ni(II and Cu(II)) were synthesized . The ligand was prepared in two steps. In the first step a solution of (terphthalaldehyde) in methanol reacts under reflux with (p-aminoacetophenone) to give an intermediate compound [1-[3-({4-[(3-Acetyl-phenylimino)-methyl]-benzylidene}-amino)-phenyl]- ethanone which reacts in the second step with (2-Amino-phenol) giving the mentioned ligand. The complexes were synthesized by addition the corresponding metal salt solution to the solution of the ligand in methanol under reflux in (1:1) metal to ligand ratio. On the basis of, molar conductance, I.R., UV-Vis, HPLC, chlorid

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Publication Date
Wed Jun 10 2015
Journal Name
Ibn Al-haitham Journal For Pure And Applied Science
New Schiff Base Derived From Folic Acid and 3- Aminoacetophenone and its Metal Complexes with Some Transition Metals and Evaluation of Their Biological Activity
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The ligand [Potassium (E)-(4-(((2-((1-(3-aminophenyl) ethylidene) amino)-4-oxo-1,4- dihydropteridin-6-yl) methyl) amino)benzoyl)-L-glutamate] was prepared from the condensation reaction of folic acid with (3-aminoacetophenone) through Schiff reaction to give a new Schiff base ligand [H2L]. The ligand [H2L] was characterized by elemental analysis CHN, atomic absorption (A.A), (FT-I.R.), (U.V.-Vis), TLC, E.S. mass (for spectroscopes), molar conductance, and melting point. The new Schiff base ligand [H2L], reacts with Mn(II), Co(II), Ni(II), Cu(II), Cr(III) and Cd(II) metal ions and (2-aminophenol), (metal : derivative ligand : 2-aminophenol) to give a series of new mixed complexes in the general formula:- K3[M2(HL)(HA)2], (where M=Mn(II) and

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