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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 Jun 30 2020
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Investigation of Ozone Microbubbles for the Degradation of Methylene Orange Contaminated Wastewater
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   In the present study, semi – batch experiments were conducted to investigate the efficiency of ozone microbubbles (OMBs) in the treatment of aqueous dye solutions methylene orange under different reaction conditions such as  effect of initial solution pH , ozone generation rate and initial MO-concentration. The results showed that the removal of MO by OMBs were very high at the acidic and alkaline media and upon increasing the generation rate of ozone from 0.498 to 0.83 mg/s, the removal efficiency dramatically increased from 75to 100% within 15 min. The rate of oxidation reaction followed a pseudo first- order kinetic model. The results demonstrated that OMBs is efficient in terms of the decline of methylene orange c

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Wed May 03 2017
Journal Name
Petroleum Science And Technology
Investigation of non-Newtonian flow characterization and rheology of heavy crude oil
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Sun Oct 03 2021
Journal Name
Journal Of Interdisciplinary Mathematics
Application of topological concepts to the investigation of COVID-19 (modified) symptoms
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We examine 10 hypothetical patients suffering from some of the symptoms of COVID 19 (modified) using topological concepts on topological spaces created from equality and similarity interactions and our information system. This is determined by the degree of accuracy obtained by weighing the value of the lower and upper figures. In practice, this approach has become clearer.

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Tue Jul 02 2019
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Experimental Investigation of the Behavior of Self-Form Segmental Concrete Masonry Arches
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This research aims to introduce a new technique-off-site and self-form segmental concrete masonry arches fabrication, without the need of construction formwork or centering. The innovative construction method in the current study encompasses two construction materials forms the self-form masonry arches, wedge-shape plain concrete voussoirs, and carbon fiber-reinforced polymer (CFRP) composites. The employment of CFRP fabrics was for two main reasons: bonding the voussoirs and forming the masonry arches. In addition, CFRP proved to be efficient for strengthening the extrados of the arch rings under service loadings. An experimental test was conducted on four sophisticated masonry arch specimens. The research parameters were the Keystone thic

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Sun Jan 01 2023
Journal Name
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HRM Management Approaches, With a Focus on Employee Centric Approach: A Case Study In The Rafidain Bank In Iraq
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This research attempts to shed light on a topic that is considered one of the most important topics of HRMs management, which is the Employee centric approach by examining its philosophy and understanding . To achieve the goal, the research relied on the philosophical analytical method, which is one of the approaches used in theoretical studies. The research reached a set of conclusions, the most important of which are the theoretical studies that addressed this entry in the English language and the lack of it in the Arabic language, according to the researcher's knowledge. The research reached a set of recommendations, the most important of which was that this approach needs more research, analysis and study at the practical and th

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Publication Date
Fri Oct 01 2010
Journal Name
Iraqi Journal Of Physics
Investigation of plasma characteristics of center region of post cylindrical magnetron sputtering device
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A d.c. magnetron sputtering system was designed and fabricated. The chamber of this system is consisted from two copper coaxial cylinders. The inner one used as the cathode and the outer one used as anode with magnetic coil located on the outer cylinder (anode). The axial behavior of the magnetic field strength along the cathode surface for various coil current (from 2A to 14A) are shown. The results of this work are investigated by three cylindrical Langmuir probes that have different diameters that are 2.2mm, 1mm, and 0.45mm. The results of these probes show that, there are two Maxwellian electron groups appear in the central region. As well as, the density of electron and ion decreases with increases of magnetic field strengths.

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Publication Date
Tue Jul 19 2022
Journal Name
Arabian Journal For Science And Engineering
Investigation of the Impacts of Nanomaterials on the Micromechanical Properties of Gypseous Soils
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Mon Feb 01 2021
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Study and Investigation of Hard Photons Emission in Heavy Ion Collisions
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This work involves hard photon rate production from quark -gluon plasma QGP interaction in heavy ion collision. Using a quantum chromodynamic model to investigate and calculation of photons rate in 𝑐𝑔 → 𝑠𝑔𝛾 system due to strength coupling, photons rate, temperature of system, flavor number and critical. The photons rate production computed using the perturbative strength models for QGP interactions. The strength coupling was function of temperature of system, flavor number and critical temperature. Its influenced by force with temperature of system, its increased with decreased the temperature and vice versa. The strength coupling has used to examine the confinement and deconfinement of quarks in QGP properties and inf

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Fri Jun 01 2007
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Investigation of heat transfer phenomena and flow behavior around electronic chip
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Computational study of three-dimensional laminar and turbulent flows around electronic chip (heat source) located on a printed circuit board are presented. Computational field involves the solution of elliptic partial differential equations for conservation of mass, momentum, energy, turbulent energy, and its dissipation rate in finite volume form. The k-ε turbulent model was used with the wall function concept near the walls to treat of turbulence effects. The SIMPLE algorithm was selected in this work. The chip is cooled by an external flow of air. The goals of this investigation are to investigate the heat transfer phenomena of electronic chip located in enclosure and how we arrive to optimum level for cooling of this chip. These par

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Publication Date
Fri Mar 01 2019
Journal Name
Iraqi Journal Of Physics
Spectroscopic investigation of Rhodamine-B thin film prepared by PLD technique
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Optical properties of Rhodamine-B thin film prepared by PLD
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1064nm and 532 nm laser wavelength of different laser pulse
energies shows that all the curves contain two bands, B band and Q
bands with two branches, Q1 and Q2 band and a small shift in the
peaks location toward the long wavelength with increasing laser
energy. FTIR patterns for Rhodamine-B powder and thin film within
shows that the identified peaks were located in the standard values
that done in the previous researches. X-ray diffraction patterns of
powder and prepared Rhodamine-B thin film was display that the
powder has polycrystalline of tetragonal structure, while the thin film

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