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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 08 2021
Journal Name
Baghdad Science Journal
Study the effect of aqueous extract of Yas Rue on the types of bacteria isolated from wounds and burns
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The current study was conducted to determine the sensitivity of some pathogenic bacterial isolates isolated from wounds and burns water toward the disposer of the Yas Rue tested five crude bacterial isolates isolated from wounds and burns which these isolates sensitive to aqueous extract crude

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Publication Date
Tue Jan 01 2019
Journal Name
International Journal Of Civil Engineering And Technology
PREDICTION OF BEARING CAPACITY, ANGLE OF INTERNAL FRICTION, COHESION, AND PLASTICITY INDEX USING ANN (CASE STUDY OF BAGHDAD, IRAQ).
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In the last few years, the use of artificial neural network analysis has increased, particularly, in geotechnical engineering problems and has demonstrated some success. In this research, artificial neural network analysis endeavors to predict the relationship between physical and mechanical properties of Baghdad soil by making different trials between standard penetration test, liquid limit, plastic limit, plasticity index, cohesion, angle of internal friction, and bearing capacity. The analysis revealed that the changes in natural water content and plastic limit have a great effect on the cohesion of soil and the angle of internal friction, respectively. . On the other hand, the liquid limit has a great impact on the bearing capacity and

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Publication Date
Sun Jul 01 2018
Journal Name
Journal Of Pharmaceutical Sciences And Research
Study of Environmental and Biological characteristics of AL-Chibaish marshes and their effect to the biodiversity of southern Iraq
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The Mesopotamian marshlands faced a massive destruction from many years and this lead to effect to ecosystem. In this study a survey was made on the physical chemical and heavy metals characteristics and microbiological analysis of AL Chibaish marsh during the two months. Water analyses revealed unacceptable values for almost all physiochemical and biological properties, according to WHO standard limits for drinking water. Almost all major ions and heavy metal concentrations in water showed a distinct decreasing trend at the marsh outlet station compared to other stations. In general, major and minor ions, as well as heavy metals exhibit higher concentrations in location 1 than in location 3. The concentrations of heavy metals in water show

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Publication Date
Tue Jul 30 2024
Journal Name
Iraqi Journal Of Science
The Influence of Sucrose on Biomass and Glycosides Content of Callus Cultured from the Leaves of Stevia rebaudiana Berton
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Stevia rebaudiana Bertoni contains diterpenoid steviol glycosides that have no adverse impact on blood sugar levels despite being 300 times sweeter than sugar. This study aimed to investigate the rate of callus induction from stevia leaves and the content of glycosides when changing the sucrose percentage in the culture medium.. Murashige and Skoog (MS) culture medium supported by 4.0 mg/l naphthalene acetic acid (NAA) and 1.0 mg/l benzyl adenine (BA) was used, and different concentrations of sucrose (2, 3, 4, 5 and 6%) were tested .The extraction of glycosides from leaf and callus tissues was performed by using methanol. Extracted glycosides were analyzed by high-performance liquid chromatography (HPLC). The results showed signific

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Publication Date
Sun Sep 03 2017
Journal Name
Baghdad Science Journal
A study of histological changes in the Diaphragm of male albino mice administered with aqueous extract of chamomileflowers Chamomillarecutita
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The chamomile is one of the most important medicinal plants recommended for treatment of asthma and some respiratory system diseases. This research was designed to research the effects of aqueous extract of chamomillarecutita on histological structure of Diaphragm of albino mice. The study included 40 male albino mice Musmusculus, their age ranged from (5-7) weeks.The mices were divided randomly to 5 groups and oral administered with 1 ml every day for 10 days:- First Group G1: consider as control group and treated with normal saline,Second Group G2: was treated with aqueous extract of chamomile with concentration of 3 gm /100 ml D.W, Third Group G3: was treated with aqueous extract of chamomile with concentration of 5 gm /100 ml D.W.Fourth

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Publication Date
Thu Mar 01 2018
Journal Name
مجلة الباحث في العلوم الإنسانية و الإجتماعية
The Rate of Performance of Scientific Committees in the University of Baghdad in Accordance to the Department’s Heads’ Viewpoint
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The research aims at recognition of The rate of performing tasks done by the scientific committees in the scientific departments in the University of Baghdad, within the evaluative perspective of the departments’ Heads. To find any statistically significant differences in the responses of the research sample to the rates performance of the scientific committees in scientific departments in the University of Baghdad, within the evaluative perspective of the departments’ Heads, according to the two variables of the social gender; male and females, and field of specialization of Scientific and Humanities. The research sample consisted if (107) heads of the scientific department in the University of Baghdad. The researchers designed a

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Publication Date
Fri Jun 24 2022
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The role of incentive legislation in job creativity: An applied study of a sample of Babylon Technical Institute employees
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The Incentives legislation aims to raise the efficiency of job performance of all kinds through optimal investment of human resources and their capabilities to raise or increase and production influence and provide distinguished and creative services such as The Incentives Law of Productive Ministries Employees No. 20 of 1993 and instructions issued by ministries and relevant Facilities regarding incentives for their affiliates based on provisions Public Companies Law and the instructions of the Higher Education Fund issued by the Ministry of Higher Education and Scientific Research. The human element is the most unstable and complex element of production as it is characterized by a set of feelings and emotions that is expresses

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Publication Date
Wed Sep 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of Alkaline Phosphatase, Salivary Flow Rate and Salivary Potential of Hydrogen in Relation to Severity of Chronic Periodontitis
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Background: The cells of periodontium contain many intracellular enzymes like (alkaline phosphatase ALP) that are released outside into the saliva and gingival crevicular fluid (GCF) after destruction of periodontal tissue. The aim of study was to determine the activity of this enzyme in saliva and its relation to the salivary flow rate, PH and clinical periodontal parameters in patients with chronic periodontitis. Subject, Materials and methods: Sample population consist of 75 individuals ;divided into four groups , the first group (15):control subject, the second group (20):mild chronic periodontitis, the third group(20) moderate chronic periodontitis and the fourth group (20) sever chronic periodontitis, Measurements of plaque index (PL

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Publication Date
Fri Jan 01 2010
Journal Name
Bn Al-haitham Journal For Pure And Applied Sciences
Effects of Different Levels of Urea and Superphosphate Fertilizer in Some Growth Characters and the Yield of Fenugreek plant
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جريت التجربة في اصص فخارية سعة كل اصيص 4 كغم تربة في البيت الزجاجي التابع لقسم علوم الحياة/كلية التربية ابن الهيثـــــــــم/جـامعــة بـغداد لموســم النمـو 2008-2009 لدراســة تأثيــر اربعـــة مستويـــــات من سمــــاد اليوريـــا وهي (0, 0.1, 0.2, 0.4) غم/اصيص والتي تعادل (0, 100, 200, 400) كغم/هكتار وثلاث مستويات من سماد السوبر فوسفات وهي (0, 0.1, 0.2) غم/اصيص والتي تعادل (0, 100, 200) كغم/هكتارفي مكونـات الحاصـــل لنبــات الحلبـــة Trigonella foe

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Publication Date
Sun Feb 15 2026
Journal Name
Journal Of Baghdad College Of Dentistry
An Evaluation the Effect of Alcohol Presence in Mouth Washes on Force Degradation of Different Configurations of Elastomeric Chains
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Background: Elastomeric chains are one of the most commonly used force delivery systems. They have the ability to exert a continuous force, convenience of use, compatibility to oral environment and cost effectiveness but one of the inherited disadvantages is force degradation. Materials and methods: This in vitro study was designed to evaluate the effect of alcohol presence in mouthwashes on force decay of different configurations of clear elastomeric chains from (Ortho Technology company) which are: closed , short and long under the effect of time at (Initial, 1, 2, 3 and 4 weeks) intervals with exposure to different chemical solutions. A total (540) modules of elastomeric chains of three different types (long, short and closed) trans

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