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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 Apr 19 2022
Journal Name
Chemical Methodologies
Biosynthesis, Characterization, and Applications of Bismuth Oxide Nanoparticles Using Aqueous Extract of Beta Vulgaris
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Bismuth oxide nanoparticle Bi2O3NPs has a wide range of applications and less adverse effects than conventional radio sensitizers. In this work, Bi2O3NPs (D1, D2) were successfully synthesized by using the biosynthesis method with varying bismuth salts, bismuth sulfate Bi2(SO4)3 (D1) or bismuth nitrate. Penta hydrate Bi(NO3)3.5H2O (D2) with NaOH with beta-vulgaris extract. The Bi2O3NPs properties were characterized by different spectroscopic methods to determine Bi2O3NPs structure, nature of bonds, size of nanoparticle, element phase, presence, crystallinity and morphology. The existence of the Bi2O3 band was verified by the FT-IR. The Bi2O3 NPs revealed an absorption peak in the UV-visible spectrum, with energy gap Eg = 3.80eV. The X-ray p

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Publication Date
Sat Aug 01 2020
Journal Name
Iop Conference Series: Materials Science And Engineering
Effects of Sandy Soil-structure Interaction on the Natural Period of RC Building Frames
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Abstract<p>Building natural period, T, is a key character in building response for wind and seismic induced forces. In design practice, the period, T, is either estimated from empirical relations proposed by the design codes or determined from analytical or numerical models. The effect of the soil-structure interaction is usually neglected in the design practice and analysis models. This paper uses a sophisticated finite element simulation to investigate the effect of soil-structure modeling on the fundamental period of RC buildings subjected to wind and seismic induced forces. A typical interior building frame has been imitated using the frame element for beams and columns with constrains to mo</p> ... Show More
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Publication Date
Sun Jan 01 2017
Journal Name
Euphrates Journal Of Agriculture Science
EFFECT OF ERRIGATION WATER SALINITY ON OAT SEEDS OF SOME CULTIVAR (Avena sativa L.)
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The study was conducted to investigate the effect of salinity of irrigation water on seeds quality and seedling growth characters for three oat cultivars (Shifaa, Hamel and Pimula) . It was carried oat in seed technology laboratory, field crops department, College of Agriculture, Baghdad University of Aljadiriya for period of tow years. Seeds of three oat cultivars (Shifaa, Hamel and Pimula) taken from a field experiment conducted during 2014-2015 and 2015-2016 irrigated with three salinity water levels (3, 6 and 9 dS.m-1 ) in addition to river water with salinity level of 1.164 dS.m-1 as control. Seeds were tested in laboratory experiments to estimate their quality, and completely randomized design with three replicates was used. Statistic

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Publication Date
Thu Feb 26 2026
Journal Name
Journal Of Baghdad College Of Dentistry
The Effect of Multi-Wall Carbon Nanotubes on the Microhardness of the Tooth Enamel
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Background: The objectives of this study are to evaluate the effect of addition of Multi-Wall Carbon Nano Tubes (MWCNTs) of different concentrations (0.05 mg.mL-1,0.25 mg.mL-1,0.5 mg.mL-1and1 mg.mL-1) on dimethyl sulphoxide DMSO and distilled water (DW) on tooth enamel. It intends to evaluate enamel microhardness in (Kg. m-2) pre and post the application of Multi-Wall Carbon Nano Tubes (MWCNTs). Materials and Methods: Thirty specimens prepared for the present study to measure the hardness of the enamel. Results: The results showed that a significant increase in the enamel microhardness for groups 0.05 mg/mL (group B), 0.25 mg/mL (group C), 0.5 mg/mL (group D) and 1 mg/mL (group E) compared with control group (group A) in dimethyl sulphoxi

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Publication Date
Thu Nov 11 2021
Journal Name
Aip Conf. Proc
Effect of cobalt Ions precursor on the nanostructure of sprayed cobalt oxide thin films
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In this study, Cobalt Oxide nanostructure was successfully prepared using the chemical spray pyrolysis technique. The cobalt oxide phase was analysed by X-ray Diffraction (XRD) and proved the preparation of two cobalt oxide phases which are Co3O4 and CoO phases. The surface morphology was characterized by Scanning Electron Microscope (SEM) images showing the topography of the sample with grain size smaller than 100 nm. The optical behavior of the prepared material was studied by UV-Vis spectrophotometer. The band gap varied as 1.9 eV and 2.6 eV for Co3O4 prepared from cobalt sulphate precursor, 2.03 eV and 4.04 eV for Co3O4 prepared from cobalt nitrate precursor, 2.04 eV and 4.01 eV for CoO prepared from cobalt chloride precursor where th

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Publication Date
Sun Mar 07 2010
Journal Name
Baghdad Science Journal
Studying the ability of transformation of lymphocytes by using PHA in patient with Cytomegalovirus
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Publication Date
Sun Nov 01 2020
Journal Name
Iop Conference Series: Materials Science And Engineering
Kinetic Study of Adsorption of Malachite Green Dye on Poly Aniline-Formaldehyde/Chitosan Composite
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Abstract<p>Poly aniline-formaldehyde/chitosan composite (PAFC) was prepared by the in situ polymerization method. It was characterized by FTIR spectroscopy in addition to SEM, EDS and TGA techniques. The adsorption kinetics of malachite green dye (MG) on (PAFC) were studied for various initial concentrations (20, 30 and 40) mg/L at three temperatures (308, 313 and 318) K. The influence factors of adsorption; adsorbent dose, contact time, initial concentration and temperature were investigated. The kinetic studies confirmed that adsorption of MG obeyed the pseudo-second-order model and the adsorption can be controlled through external mass transfer followed by intraparticle diffusion mass transfer. A study of th</p> ... Show More
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Publication Date
Sun Dec 07 2008
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Synthesis of New Heterocyclic Compounds Derived from Anthrone and Evaluation of Their Biological Activity
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Publication Date
Wed May 27 2015
Journal Name
Diyala Journal For Pure Science
Synthesis And Characterization Of Some New Metals Complexes Of [N-(3-acetylphenylcarbamothioyl)-4-methoxybenzamide]
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Publication Date
Fri Feb 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
Reflecting the Faithful economic representation of accounting practices on the quality of accounting information
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Where the accounting system in Iraq is still using many of these accounting practices according to the legal requirements to measure assets and liabilities away from the measurement that results in information representing the economic essence and represent honestly the financial situation and financial performance and future cash flows, and the needs of users of financial reports to useful accounting information adopted The International Accounting Standards Board (IASB) represents the true representation of accounting information in accordance with the concept of economic substance, which is the basis for the preparation and development of international accounting standards, and because accounting is part of the

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