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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
Mon Mar 27 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Design, Synthesis and Preliminary Antimicrobial Evaluation of New Derivatives of Cephalexin
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There is a continuous and massive need for newer cephalosporins that should have resistance against β-lactamases and can be used orally. An approach of using cephalexin, as a well-studied and potent antibacterial compound is considered to prepare new designed derivatives.  These derivatives include the incorporation of amino acid moiety linked through an amide bond with the α-amino group of cephalexin. Certain aliphatic amino acids were used, such as glycine, alanine, valine and proline. The chemical structures of these derivatives were confirmed by IR spectroscopy and elemental analyses. All the synthesized compounds were subjected for preliminary evaluation of antimicrobial activity using well diffusion method, against certa

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Publication Date
Wed Oct 23 2019
Journal Name
Iraqi Journal Of Agricultural Sciences
EXTRACTION OF JOJOBA OIL USING VARIOUS CONCENTRATIONS OF TWO DIFFERENT SOLVENTS
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The aim of this study was extraction of jojoba oil using different solvents. A mixture of waterhexane and water-ethanol are used as solvents to extract jojoba oil in a batch extraction process and compared with a pure solvent extraction process. The effects of particle size of crushed seeds, solvent-to-water ratio and time on jojoba oil extraction were investigated. The best recovery of oil was obtained at the boiling temperature of the solvent and four hour of extraction time. When seed particle size was 0.45 mm and a pure ethanol was used (45% yield of oil extraction), whereas, it was 40% yield of oil at 25% water-hexane mixture. It was revealed that the water-ethanol and water-hexane mixtures have an effect on the oil extraction yield. T

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Publication Date
Sat Dec 14 2019
Journal Name
Journal Of The College Of Education For Women
Analysis of the Structure of Scientific News Headlines in Online Newspapers
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Newspaper headlines are described as compressed and ambiguous pieces of discourse that represent the bodies of the articles. Their main function is to provide the readers with an informative message they would have no prior idea about. Ifantidou (2009) claims that the function of a headline is to get the readers’ attention rather than providing information because it does not have to represent the whole of the article it refers to. This paper aims at examining this hypothesis in relation to scientific news headlines reported by a number of news agencies. The paper follows Halliday (1967) information structure theory by applying it on ten selected headlines; each two headlines represent one scientific discovery reported by different new

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Publication Date
Fri Aug 07 2020
Journal Name
Key Engineering Materials
The Effect of Particle Size Distribution on some Properties of Gypsum
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Gypsum is one of the important construction materials in Iraq in plastering surfaces and gypsum board , the ability of gypsum to give a comfortable an aesthetic ambiance as a construction material increase the need of gypsum , The particle size , total surface area and particle size distribution were factors affecting plaster properties used for construction properties . In this study gypsum paste was used with different mixing ratios of particle size and studied the physical properties of these types of pastes named (standard consistency ,setting time ,density) and compressive strength . The results showed that the water to gypsum ratio increased with increasing the fineness of the gypsum to (0.75%) and the setting time to the maxi

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Publication Date
Wed Oct 24 2018
Journal Name
Journal Of Economics And Administrative Sciences
The rality of urban management strategies in the city of Baghdad
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Several studies have indicated that more than 600 cities in the world (intermas of rapid growth and development) will generate about 60% of international economic growth between 2010 and 2025 . by 2025 , 66% of the worlds population will live in urban areas the management of cities will face challenges that accompany this increase in the population which requires preparing to face these challenges and problems and the need to provide the aim of the research to know the readiness of Baghdad city to implement the strategies of urban management throught on asmple representing the ( Advisiry group for the comprechnsive development plan for the city of Baghdad 2030 and its supporters ) in the municipality of Baghdad and the number of

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Publication Date
Sun Feb 03 2019
Journal Name
Journal Of The College Of Education For Women
OIL OF IRAQ AND MULTI-NATIONALITIES COMPANIES "Geopolitical point of view"
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Multi-nationalities companies are the main companies in the progressed
countries that improve the current technology and, thus, become the main source of it.
These companies, in the first place, aim to increase the profits of its
investments to satisfy stock holders in the original countries to which these companies
belong.
It is a mean to interfere in the economic of countries especially the growing
ones and exploit their important natural resources. Since this research focus on the
dangers of these companies, mechanism of its work and its dangers on the most
important natural resources of our country which is oil; therefore, the research
confirm that this important natural treasure must be under an Iraqi cont

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Publication Date
Mon Sep 30 2024
Journal Name
Malaysian Journal Of Science
DEVELOPMENT OF A SPECTROPHOTOMETRIC DETERMINATION OF PREDNISOLONE IN DIFFERENT DOSAGE FORMS
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A sensitive, accurate, and affordable colorimetric method was developed for assaying prednisolone (PRZ) in various medicinal forms. The procedure involves the oxidation of PRZ by ferric ions, followed by complexation of the resulting ferrous ions with ferricyanide to produce a greenish-blue product. Common complexation conditions were thoroughly investigated. The mole ratio of FeCl₃·6H₂O to K₃Fe(CN)₆ was 8:1. The proposed mechanism of complexation was suggested and considered. Various parameters were optimized, including the reduction of the colorimetric reaction temperature to 50°C and the duration of heating and analysis to 20-30 minutes. The calibration curve was linear over the range of 1-60 µg/mL. The limit of detection (LOD

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Publication Date
Tue Feb 05 2019
Journal Name
Journal Of The College Of Education For Women
Biography of the Last The formation of the ancient Pharaonic Warrior
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Cash studies on Biography few self, compared to what feet of analysis and criticism in the other arts as (novel, short story, poetry, theater, painting), however, is a biographical articles in the relatively few Arabic literature as presented in the other Arts, has taken this Art greater opportunity in our literature with his Taha Hussein (days), or (my life) to Ahmed Amin, or Fadwa Toukan (a nice trip, and difficult journey), or Jabra Ibrahim Jabra in the (first well) or (Princess Street), which forms taken from the self point of departure the desire to write a CV to try to familiarize readers with the information possible to the same creator, the remainder (ego) is the axis basis in a CV, gradually, starting from childhood through yout

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Publication Date
Wed Jan 01 2020
Journal Name
Route Educational And Social Science Journal
SURVIVAL IN TIMES OF PANDEMICS: THE PROPHETIC VISION OF JACK LONDON
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Publication Date
Sun Jan 01 2023
Journal Name
Iraqi Journal Of Applied Physics
Fabrication and Improvement of Optoelectronic Properties of Copper Chalcogenide Thin Films
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