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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 01 2021
Journal Name
Int. J. Nonlinear Anal. Appl.
Study of the dual ideal of ku-algebra
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In this work, we apply the notion of a filter of a KU-Algebra and investigate several properties. The paper defined some filters such as strong filter, n-fold filter and P-filter and discussed a few theorems and examples.

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Publication Date
Sun Nov 04 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Determination of Quality of Life for Adult Patients
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Objective: The study aimed to determine quality of life domains for adult patients with limbs loss and to identify
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Methodology: A descriptive study was carried out at Baghdad artificial limb center, Al-Salam medical
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Publication Date
Sun Dec 01 2019
Journal Name
Acoustical Society Of America
Effect of ultrasonic pretreatment on pyrolysis of microalgae
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Sat Feb 15 2025
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Analysis of applications of Banach fixed point theorem
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In the context of normed space, Banach's fixed point theorem for mapping is studied in this paper. This idea is generalized in Banach's classical fixed-point theory. Fixed point theory explains many situations where maps provide great answers through an amazing combination of mathematical analysis. Picard- Lendell's theorem, Picard's theorem, implicit function theorem, and other results are created by other mathematicians later using this fixed-point theorem. We have come up with ideas that Banach's theorem can be used to easily deduce many well-known fixed-point theorems. Extending the Banach contraction principle to include metric space with modular spaces has been included in some recent research, the aim of study proves some pro

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Journal Name
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Clinical importance of gingival biotype (Review of literature)
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This review discusses the gingival biotypes, their characteristics, analysis based on the measurement of the dentopapillary complex. Also discuss their response to inflammation, surgery, and ridge healing after tooth extraction, their influence in the behavior of the peri-implant tissue

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Tue Mar 01 2016
Journal Name
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Analysis of Recorded Inflow Data of Ataturk Reservoir
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Since the beginning of the last century, the competition for water resources has intensified dramatically, especially between countries that have no agreements in place for water resources that they share. Such is the situation with the Euphrates River which flows through three countries (Turkey, Syria, and Iraq) and represents the main water resource for these countries. Therefore, the comprehensive hydrologic investigation needed to derive optimal operations requires reliable forecasts. This study aims to analysis and create a forecasting model for data generation from Turkey perspective by using the recorded inflow data of Ataturk reservoir for the period (Oct. 1961 - Sep. 2009). Based on 49 years of real inflow data

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Wed Mar 01 2023
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Let  be a non-trivial simple graph. A dominating set in a graph is a set of vertices such that every vertex not in the set is adjacent to at least one vertex in the set. A subset  is a minimum neighborhood dominating set if  is a dominating set and if for every  holds. The minimum cardinality of the minimum neighborhood dominating set of a graph  is called as minimum neighborhood dominating number and it is denoted by  . A minimum neighborhood dominating set is a dominating set where the intersection of the neighborhoods of all vertices in the set is as small as possible, (i.e., ). The minimum neighborhood dominating number, denoted by , is the minimum cardinality of a minimum neighborhood dominating set. In other words, it is the

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Mon Mar 07 2022
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The level of Mental Mindfulness of College of Education Students at Umm Al-Qura University in the light of Corona Pandemic
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The aim of this research is to identify the level of mental mindfulness among female students of the College of Education at Umm Al-Qura University, as well as to identify the statistically significant differences in the level of mental mindfulness according to academic level, specialization, and academic achievement. A mental mindfulness scale was designed to cover five dimensions. The study employed the analytic descriptive approach applied to a random sample of (217) female students from various academic specializations. The findings indicated that the level of mental mindfulness was average among female students. Statistically significant differences were attributable to the academic level, academic specializations, and academic achi

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Publication Date
Mon Jun 30 2025
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