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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 01 2019
Journal Name
International Journal Of Mechanical Engineering And Technology (ijmet)
INVESTIGATION THE PROPERTIES OF SILICONE RUBBER BLEND REINFORCED BY NATURAL NANOPARTICLES AND UHMWPE FIBER
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Many faces are exposed to degradation, discoloration, changes in humidity. The primary objective has improved some properties of hybrid nanocomposites materials that used for restoring of the function maxillofacial prosthesis and improving the esthetic. In the present research different lengths chopped and continuous of ultrahigh molecular weight polyethylene (UHMWPE) fiber was added at selected percentage (0.0, 0.2% and 1%) to polymer blend composite (95%SR /5%PMMA: 0.2% Pomegranate Peels Powder (PPP)) for developing the properties of silicone rubber used for the maxillofacial prosthesis applications. Some mechanical and physical properties were done on the all prepared samples. The results showed that all properties have improved when add

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Publication Date
Thu Dec 01 2016
Journal Name
Journal Of Engineering
Experimental Investigation of Natural Convection into a Horizontal Annular Tube with Porous Medium Effects
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In this work, an experimental investigation has been done for heat transfer by natural-convection through a horizontal concentric annulus with porous media effects. The porous structure in gap spacing consists of a glass balls and replaced by plastic (PVC) balls with different sizes. The outer surface of outer tube is isothermally cooled while the outer surface of inner tube is heated with constant heat flux condition. The inner tube is heated with different supplied electrical power levels. Four different radius ratios of annulus are used. The effects of porous media material, particles size and annulus radius ratio on heat dissipation in terms of average Nusselt number have been analyzed.

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Publication Date
Sat Dec 02 2023
Journal Name
Journal Of Engineering
Simulation and Experimental Investigation of Performance and Flow Behavior for Steam Ejector Refrigeration System
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The ejector refrigeration system is a desirable choice to reduce energy consumption. A Computational Fluid Dynamics CFD simulation using the ANSYS package was performed to investigate the flow inside the ejector and determine the performance of a small-scale steam ejector. The experimental results showed that at the nozzle throat diameter of 2.6 mm and the evaporator temperature of 10oC, increasing boiler temperature from 110oC to 140oC decreases the entrainment ratio by 66.25%. At the boiler temperature of 120oC, increasing the evaporator temperature from 7.5 to 15 oC increases the entrainment ratio by 65.57%. While at the boiler temperature of 120oC and

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Publication Date
Wed Jan 01 2025
Journal Name
Journal Of Advanced Veterinary And Animal Research
Investigation and genetic confirmation of the Cryptosporidium species in fish handlers in Baghdad city
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Objective: The present study aims to investigate molecular confirmation for <i>Cryptosporidium</i> species in fish handlers in Baghdad City, central Iraq. Materials and Methods: Sixty stool samples were collected between early November 2023 and late April 2024. All samples were examined phenotypically using a modified Ziehl-Neelsen stain and genotypically (nested polymerase chain reaction technique) based on a partial sequence of 18S rRNA genes with sequencing and phylogenetic tree analysis. Results: The total molecular results identified <i>Cryptosporidium parvum</i> with an infection rate of 45% (27/60). A higher infection rate of 51.9% (14/27) was found in the age group between 15 and 35 years, and male

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Publication Date
Thu Oct 31 2013
Journal Name
Al-khwarizmi Engineering Journal
An Investigation Study of Thinning Distribution in Single Point Incremental Forming Using FEM Analysis
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Single Point Incremental Forming (SPIF) is a forming technique of sheet material based on layered manufacturing principles. The sheet part is locally deformed through horizontal slices. The moving locus of forming tool (called as toolpath) in these slices constructed to the finished part was performed by the CNC technology. The toolpath was created directly from CAD model of final product. The forming tool is a Ball-end forming tool, which was moved along the toolpath while the edges of sheet material were clamped rigidly on fixture.

This paper presented an investigation study of thinning distribution of a conical shapes carried out by incremental forming and the validation of finite element method to evaluate the limits of the p

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Publication Date
Tue Feb 27 2018
Journal Name
Iraqi Journal Of Laser
Investigation of Densified SiO2 Sol-Gel Thin Films Using Conventional and DPSS Laser Techniques
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The prepared nanostructure SiO2 thin films were densified by two techniques (conventional and Diode Pumped Solid State Laser (DPSS) (532 nm). X-ray diffraction (XRD), Field Emission Scanning electron microscopy (FESEM), and Atomic Force Microscope (AFM) technique were used to analyze the samples. XRD results showed that the structure of SiO2 thin films was amorphous for both Oven and Laser densification. FESEM and AFM images revealed that the shape of nano silica is spherical and the particle size is in nano range. The small particle size of SiO2 thin film densified by DPSS Laser was (26 nm) , while the smallest particle size of SiO2 thin film densified by Oven was (111 nm).

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Publication Date
Sun Jul 09 2023
Journal Name
Journal Of Engineering
An Investigation into Thermal Performance of Mist Water System and The Related Consumption Energy
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Experimental tests were conducted to investigate the thermal performance (cooling effect) of water mist system consisting of 5μm volume median diameter droplets in reducing the heat gain entering a room through the roof and the west wall by reducing the outside surface temperature due to the evaporative cooling effect during the hot dry summer of Baghdad/Iraq. The test period
was Fifty one days during the months May, June, and July 2012. The single test day consists of 16 test hours starting from 8:00 am to 12:00 pm. The results showed a reduction range of 1.71 to 15.5℃ of the roof outside surface temperature and 21.3 to 76.6% reduction in the daily heat flux entering the room through the roof compared with the case of not using w

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Publication Date
Wed Feb 05 2020
Journal Name
Journal Of Physical Education
The Effect of Group Investigation Model on Learning overhead and underarm Pass in Volleyball
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Volleyball is one of the sports that require physical and skill abilities thus many teaching models appeared to teach these abilities like group investigation model. The research aimed at identifying the effect of group investigation model on learning underarm and overhead passing in volleyball. The researchers hypothesized statistical differences between pre and posttests in learning underarm and overhead passing in volleyball as well as differences in posttests of controlling and experimental groups in learning underarm and overhead passing in volleyball. The researcher used the experimental method on (30) second year female students of physical education and sport sciences college/ university of Baghdad. Group investigation model was app

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Publication Date
Wed Feb 22 2023
Journal Name
Iraqi Journal Of Science
A Molecular Investigation of Phytoplasma (Candidatus Phytoplasma) Infecting Arabic Jasmine (Jasminum sambac) in Iraq
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This study was conducted to investigate phytoplasma causing a virescence disease on Arabic jasmine Jasminum sambac based on microscopy and molecular approaches. Samples were collected from symptomatic Arabic jasmine plants grown in nurseries in Baghdad-Iraq. Specimens from infected plants were prepared and Dienes stained for light microscopy examination. Phytoplasma were detected in infected plants by polymerase chain reaction (PCR) using P1/P7 and SecAfor1/SecArev3 Candidatus Phytoplasma specific primer sets. Light microscopy test showed symptomatic Arabic jasmine plants were phytoplasms infected when phloem tissues were stained with a dark blue color. PCR test confirmed the symptomatic plants were phytoplasms infected when SecAfor1/Sec

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Publication Date
Thu Dec 01 2011
Journal Name
Journal Of Engineering
An Experimental Investigation on Fatigue Properties of AA3003-H14 Aluminum alloy Friction Stir Welds
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AA3003-H14 aluminum alloy plates were welded by friction stir welding and TIG welding.
Fatigue properties of the welded joints were evaluated based on the superior tensile properties for
FSW at 1500 rpm rotational speed and 80 mm/min welding speed. However, there is not much
information available on effect of welding parameters with evolution of fatigue life of friction stir
welds. The present study experimentally analyzed fatigue properties for base, FSW, and TIG welds
of AA 3003-H14 aluminum alloy. Fatigue properties of FSW joints were slightly lower than the
base metal and higher than TIG welding.

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