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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
Wed Feb 11 2026
Journal Name
Al-anbar University Journal Of Law And Political Sciences
Evaluation of the Geneva Conventions of 1949 and the role of the protecting power to implement its provisions
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Mon Nov 07 2022
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Environmental Monitoring And Assessment
Comparison of Climate Change Impact upon Water Productivity of Winter Wheat in Northern and Southern Regions of Iraq 
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Fri Mar 01 2019
Journal Name
Al-khwarizmi Engineering Journal
Studying the Effect of Volume Fraction of Glass Fibers on the Thermal Conductivity of the Polymer Composite Materials
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In this study the effect of fiber volume fraction of the glass fiber on the thermal conductivity of the polymer composite material was studied. Different fiber volume fraction of glass fibers were used (3%, 6%, 9%, 12%, and 15%). Specimens were made from polyester which reinforced with glass fibers .The fibers had two arrangements according to the direction of the thermal flow. In the first arrangement the fibers were parallel to the direction of the thermal flow, while the second arrangement was perpendicular; Lee's disk method was used for testing the specimens. The experimental results proved that the values of the thermal conductivity of the specimens was higher when the fibers arranged in parallel direction than that when the fibers

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Fri Jan 08 2016
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Ibn Al-haitham Journal For Pure And Applied Sciences
Effect of Aqueous Leaves Extract of Coriandrum sativum on Histological Structure and Liver Function of Male Albino mice
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Medicinal plants are used to treat various diseases although little is known about their toxicity. Coriandrum sativum is one of the most commonly plants that is used to treat several physiological disorders. Thus, this study was conducted to evaluate the effect of aqueous extract of C. sativum on the structure and function of liver in male albino mice. Thirty male mice were randomly divided into three groups: Group 1 untreated (control), Group 2 and 3 were administrated orally with the aqueous extract of the plant at dose 125 and 250 mg/kg. b. w. For 30 days. The effect of the extract on liver weights, biochemical parameters as well as histological study were assessed. There were no significant difference (P>0.05) observed in relative organ

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Publication Date
Fri May 01 2020
Journal Name
Journal Of Engineering
Effect of Maximum Size of Aggregate on the Behavior of Reinforced Concrete Beams Analyzed using Meso Scale Modeling
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In this study, simply supported reinforced concrete (RC) beams were analyzed using the Extended Finite Element Method (XFEM). This is a powerful method that is used for the treatment of discontinuities resulting from the fracture process and crack propagation in concrete. The mesoscale is used in modeling concrete as a two-phasic material of coarse aggregate and cement mortar. Air voids in the cement paste will also be modeled. The coarse aggregate used in the casting of these beams is a rounded aggregate consisting of different maximum sizes. The maximum size is 25 mm in the first model, and in the second model, the maximum size is 20 mm. The compressive strength used in these beams is equal to 26 MPa.

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Publication Date
Fri Dec 15 2023
Journal Name
Al-academy
The extent of theatrical and musical arts contribute to the diagnosis And treatment of psychological problems Inmates of
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Sat Nov 01 2014
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Debulking of keloid combined with intralesional injection of methotrexate and triamcinolone versus intralesional injection of methotrexate and triamcinolone
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Sun Sep 01 2013
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Using Six-Sigma to measure the quality performance of the Department of Statistics-University of Baghdad-Case Study
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Publication Date
Fri Dec 01 2023
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A study of the Effect of Diesel Oil Contamination with Glycol on the Performance of a Diesel Engine
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Abstract<p>The performance of a diesel engine was tested with diesel oil contaminated with glycol at the engineering workshop/Department of Agricultural Machines and Equipment / College of the Agricultural Engineering Sciences at the University of Baghdad. To investigate the impact of different concentrations of glycol on the performance of a diesel engine, an experimental water-cooled four-stroke motor was utilized, with oil containing 0, 100, and 200 parts per million (ppm). Specific fuel consumption, thermal efficiency, friction power, and exhaust gas temperature were examined as performance indicators. To compare the significance of the treatments, the study employed a full randomization des</p> ... Show More
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Publication Date
Tue Mar 19 2024
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Comparison of physical characteristics of mass and luminosity function of disk systems in barred and unbarred spiral galaxies
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