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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
Fri Feb 08 2019
Journal Name
Journal Of The College Of Education For Women
Variation in the degree of Continentality climate of Iraq
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This research paper is about thevariationin the degree of Continentality climate of the
Iraq during (40) years for a number of climate station. Using Poresof formula, it is found out
that the climate of Iraq ranges between extreme Continentality and very extreme
Continentality, and that the Continentality degree is characterized with extreme frequency
from one year to another. In certain years, the degree of climate Continentality decreases
while in other years it rises in such a way that there is no similarity in the Continental degree
from one year to another for the same station.
As for the general trend of the degree of Continentality, the last years had noticed
special variations, which are divided in to thre

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Publication Date
Thu Dec 16 2021
Journal Name
Journal Of Advance Research In Chemical Sciences
Study of Schiff Bases Complexes of Trimethoprim: A Review
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Trimethoprim derivative Schiff bases are versatile ligands synthesized with carbonyl groups from the condensation of primary amines (amino acids). Because of their broad range of biological activity, these compounds are very important in the medical and pharmaceutical fields. Biological activities such as antibacterial, antifungal and antitumor activity are often seen. Transition metal complexes derived from biological activity Schiff base ligands have been commonly used.

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Publication Date
Tue Jun 14 2022
Journal Name
Al-academy
Mechanism of feedback in the theater of the oppressed
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The art of theater penetrated various scientific and human fields, as well as touching the facts and events surrounding it, and scientific innovations had a wide field, so it adopted feedback in interactive theater performances, especially the theater of the oppressed. Then came the indicators that resulted from the theoretical framework for the formation of the tool by which the research sample is analyzed, and then the chapter concluded with previous studies. As for the third chapter, it involved the research procedures, and through the research tool and the research method, and by selecting the intentional sample, the sample represented by a play (the story of Shahrour) was analyzed. As for the fourth chapter, it included the results

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Publication Date
Thu Jan 10 2019
Journal Name
Journal Of The College Of Education For Women
Types of parallelism in the poetry of Mahmoud Darwish
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This research deals with the study of types of parallelism in contemporary Arabic poetry and took the hair Mahmoud Darwish, a model for the study has been the goal of research to clarify the term parallelism and the statement of the most important types, said evidence of that in the poetry of Mahmoud Darwish

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
design of multiband reflectors adapting the concept of stack
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Designed Mirrors double and triple package adoption concept heap where they were changing the thickness of the layers within periodic basis of the pile and different ratios (p: q) in addition to change the refractive index of materials within periodic basis and its impact on sites Dhour tops high reflectivity study included spectral region visible and infrared, depending on NdharahFeatured matrix adjusted fall of light close to the vertical arrangement multilayer dielectric materials and thin films homogeneous and uniform

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Publication Date
Fri Apr 01 2016
Journal Name
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GRAPH OF EQUIVALENCE CLASSES OF A COMMUTATIVE IS-ALGEBRA
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Sun Sep 07 2008
Journal Name
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Measurements of The Spectroscopic Properties of Hydrogen Iodide Molecules
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A calculation have been carried out for determination some of the spectroscopic properties of Hydrogen Iodide HI molecules such as, the intensity of the absorption spectrum as a function of the variation of the temperature ranging from 10 to 1000 K. This study shows that the populations and hence intensity of the molecule increased as the temperature increased. Another determination of the maximum rotational quantum number Jmax of N2 , CO , BrF AgCl and HI molecules has been carried out.

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Publication Date
Mon Feb 01 2021
Journal Name
Materials Science And Engineering
Effect of magnetic water on strength properties of concrete
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Abstract<p>The research’s main goal is to investigate the effects of using magnetic water in concrete mixes with regard to various mechanical properties such as compressive, flexural, and splitting tensile strength. The concrete mix investigated was designed to attain a specified cylinder compressive strength (30 MPa), with mix proportions of 1:1.8:2.68 cement to sand to crushed aggregate. The cement content was about 380 kg/m<sup>3</sup>, with a w/c ratio equal to 0.54, sand content of about 685 kg/m3, and gravel content of about 1,020 kg/m3. Magnetic water was prepared via passing ordinary water throughout a magnetic field with a magnetic intensity of 9,000 Gauss. The strength test</p> ... Show More
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Wed Oct 07 2020
Journal Name
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Biological Activity of Complexes of Some Amino Acid: Review
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Publication Date
Sun Dec 25 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis and Atimicrobial Evaluation of Deuterated Analogues of Metronidazole
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The discovery of novel therapeutic molecules is always difficult, and there are a variety of methodologies that use the most diverse and innovative medicinal chemistry approaches. One such approach is the deuteration technique: Deuteration is the process of substituting deuterium for hydrogen in a molecule. When compared to the drug molecule, its deuterated analogues may retain the features of the original molecule and, in some cases, improve its pharmacological activity, with fewer side effects and lower toxicity. Metronidazole is a commonly used antibiotic to treat anaerobic bacterial infections, protozoal and microaerophilic bacterial infections. Met

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