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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
Mon Mar 13 2017
Journal Name
Journal Of Baghdad College Of Dentistry
The Influence of Chlorhexidine Diacetate Salt Incorporation Into Soft Denture Lining Material on Its Antifungal And Some Mechanical Properties
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Background: One of the most common problem associated with the used of soft denture lining material is microorganisms and fungal growth especially Candida albicans, which can result in chronic mucosal inflammation. The aim of this study was to evaluate the influence of chlorhexidine diacetate (CDA) salt Incorporation into soft denture lining material on antifungal activity; against Candida albicans, and the amount of chlorhexidine di-acetate salt leached out of soft liner/CDA composite. Furthermore, evaluate shear bond strength and hardness after CDA addition to soft liner Materials and methods: chlorhexidine diacetate salt was added to soft denture lining material at four different concentrations (0.05%, 0.1% and 0.2% by weight). Four hund

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Publication Date
Fri Mar 10 2017
Journal Name
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Conceptual designs of conduction cooled MgB<sub>2</sub> magnets for 1.5 and 3.0 T full body MRI systems
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Publication Date
Tue May 28 2019
Journal Name
Al-khwarizmi Engineering Journal
Heuristic D* Algorithm Based on Particle Swarm Optimization for Path Planning of Two-Link Robot Arm in Dynamic Environment
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 Finding a path solution in a dynamic environment represents a challenge for the robotics researchers, furthermore, it is the main issue for autonomous robots and manipulators since nowadays the world is looking forward to this challenge. The collision free path for robot in an environment with moving obstacles such as different objects, humans, animals or other robots is considered as an actual problem that needs to be solved.  In addition, the local minima and sharp edges are the most common problems in all path planning algorithms. The main objective of this work is to overcome these problems by demonstrating the robot path planning and obstacle avoidance using D star (D*) algorithm based on Particle Swarm Optimization (PSO)

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Sun Jun 30 2024
Journal Name
Modern Sport
Evaluating the Effectiveness of Using the Kinesthetic Teaching Style by Basketball Instructors in Practical Lessons from the Students' Perspective
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Advancements and modernizations introduced into the educational and pedagogical systems have significantly impacted teaching processes and how subjects are presented and explained to students. The focus has shifted to how learners interact with the material they need to learn, providing sufficient opportunities for learning and granting them freedom and self-confidence to achieve learning objectives. The research problem stems from the researcher's experience as a lecturer in the College of Physical Education and Sports Science, particularly in teaching basketball. She observed that some instructors were deficient in using the most effective teaching methods. The researcher formulated her research question based on these observations: "What

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Publication Date
Sat Jan 31 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Fracture resistance of endodontically treated premolars with extensive MOD cavities restored with different composite restorations (An In vitro study)
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Publication Date
Wed Jun 29 2022
Journal Name
College Of Islamic Sciences
Evidence for monotheism in Islam and the Qur’an and the meaning of the names and attributes and their unification
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This topic is considered to be of a high degree of importance to every Muslim, and its importance is due to the fact that monotheism is:

Prove that God Almighty is the God who created everything and everything opposite to monotheism is polytheism, and it is taking other than God Almighty as a deity.

Therefore, we have to know the concept of God. If he is known, then he knows the concept of monotheism and the concept of polytheism

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Publication Date
Sun Jun 30 2013
Journal Name
College Of Islamic Sciences
The Leader: His Qualifications and Attributes in the Quranic Perspective in Light of Surat Al-Naml - An Objective Study
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The world has witnessed in recent decades the development of programs and curricula, and books have been prepared showing how to prepare leaders and their industry, and what programs they should adopt

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Mon Aug 01 2011
Journal Name
J Fac Med Baghdad
Overview of breast cancerpatients and their prognostic factors treated in Baghdad teaching hospital/ oncology department in the year 2010
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Fri Dec 20 2024
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Interference with quorum sensing of Klebsiella pneumoniae by some plant extracts can affect the biofilm formation and antibiotic resistance.
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Quorum sensing (QS) is a perfectly orchestrated molecular communication system. It is a boon for Klebsiella pneumoniae, and bane for the host. This system is believed to make K. pneumoniae a leading cause of multidrug-resistant (MDR) nosocomial infections. This study aimed to investigate the antibacterial and anti-biofilm potential of medicinal plant extracts through interfering with QS of K. pneumoniae. The effect of different concentrations of ethanolic extracts of cinnamon and clove on K. pneumoniae was determined by analyzing the growth curve, survival assay (MTT), Qualitative and quantitative biofilm formation, antibiotic resistance, along with studying gene expression of the genes encoding the above traits, using quantitative real tim

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Publication Date
Sun Jun 13 2021
Journal Name
International Journal Of Drug Delivery Technology
Synthesis, Characterization and Anticorrosion Studies of New Co(II), Ni(II), Cu(II), and Zn(II) Schiff Base Complexes
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The research included preparation of new Schiff base (L) by two steps: preparation of precursor [bis(2-formyl-6-methoxyphenyl) succinate] (P) by reacting (3-methoxy salicyl aldehyde) with (succinoyl dichloride) as first step then react the prepared precursor (P) with (ethanethioamide) to have the new Schiff base [bis(2-((ethane thioyl imino) methyl)-6-methoxy phenyl) succinate] (L) as second step. Characterized compounds based on Mass spectra, 1 H, 13CNMR (for ligand (L)), FT-IR and UV spectrum, melting point, molar conduct, %C, %H, and %N, the percentage of the metal in complexes %M, magnetic susceptibility, while study corrosion inhibition (mild steel) in acid solution by weight loss. These measurements proved that by (Oxygen, Nitrogen, a

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