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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
Sat Aug 12 2017
Journal Name
Journal Of Engineering
Prepare rules spatial data for soils and the Calculation of an Area in Iraq for Industrial Purposes using Geographic Information Systems (GIS)
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Sat Feb 27 2021
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Groundwater is an essential source because of its high quality and continuous availability characterize this water resource. Therefore, the study of groundwater has required more attention. The present study aims to assess and manage groundwater quality's suitability for various purposes through the Geographical Information System GIS and the Water Quality Index WQI. The study area is located in the city of Baghdad in central Iraq, with an approximate area of ​​900 , data were collected from the relevant official departments representing the locations of 97 wells of groundwater in the study area for the year 2019, as it included physicochemical parameters such as  pH, EC, TDS, Na, K, Mg, Ca, Cl,  , and &nbs

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Mon Nov 01 2021
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Journal Of Physics: Conference Series
Light scattering detector based on light-emitting diodes-Solar cells for a flow analysis of Warfarin in pure form and pharmaceutical formulations
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Heterogeneous catalytic degradation of dye by Fenton-like oxidation over a continuous system based on Box–Behnken design and traditional batch experiments
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Light scattering detector based on light-emitting diodes-Solar cells for a flow analysis of Warfarin in pure form and pharmaceutical formulations
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Publication Date
Wed Oct 11 2023
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The Association between Emotional Intelligence and Academic Adaptation among a Sample of Gifted Students in the Intermediate and Secondary Schools in Jeddah
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This study aims to examine the relationship between emotional intelligence and academic adaptation among a sample of gifted students in intermediate and high schools in Jeddah, Saudi Arabia. The study also seeks to examine the differences between group means in emotional intelligence and academic adaptation due to demographic variables (gender and school level). In addition, the study aims to examine the role of emotional intelligence in predicting the level of academic adaptation. The researcher performed the descriptive, correlational, predictive, and comparative approaches to collect the data from a sample comprised of (309) gifted students using the emotional intelligence scale developed by Bar-on (2000), whi

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Tue Nov 25 2025
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