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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
Sun Feb 10 2019
Journal Name
Journal Of The College Of Education For Women
The Level of Spiritual Intelligence Among Students of Educational Psychology Course at Jerash University in The Light of Some variables
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This study aimed to determine the level of spiritual intelligence among students of educational psychology course at the Jerash University. and whether this level of varies depend on the gender of the student as well as the college type. The study sample consisted of (180) male and female students of bachelor students at the University Jerash, in the second semester of academic year2014-2015. The main results of the study were that the level of spiritual
Intelligence of Jerash University students was high. More over There were no statistically significant differences at the level of significance (0.05) due to the effect of gender, college type or academic achievement

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Publication Date
Mon Jan 01 2024
Journal Name
Arab Journal For Plant Protection
Effects of Aqueous and Alcoholic Extracts of Lemongrass, Cymbopogon citratus on Some Biological Aspects of the Fig Moth, Ephestia cautella
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Kamil, S.H. 2024. Effects of Aqueous and Alcoholic Extracts of Lemongrass, Cymbopogon citratus on Some Biological Aspects of the Fig Moth, Ephestia cautella. Arab Journal of Plant Protection, 42(3): 377-381. https://doi.org/10.22268/AJPP-001245 This study evaluated the effects of aqueous and ethanolic extracts of lemongrass on the third instar larvae of the date moth Ephestia cautella Walker (Lepidoptera: Pyralidae). The results obtained showed that there were toxic effects of aqueous extract, which produced the highest mortality rate of 43.35% at 5% concentration72 hours after treatment, whereas the lowest mortality rate of 17% was obtained at 0.5% concentration, 72 hours after treatment. The LC50 was 0.082%. The results indicated

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Mon Feb 16 2026
Journal Name
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The impact of strategic knowledge on strategic improvisation: an exploratory study of some private hospitals in the city of Baghdad
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Sun Dec 03 2017
Journal Name
Baghdad Science Journal
Inhibitory Effect of Bacteriophages Isolated from Sewage Water in the City of Kirkuk on some Types of Human Pathogenic Bacteria
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Most approaches to combat antibiotic resistant bacteria concentrate on discovering new antibiotics or modifying existing ones. However, one of the most promising alternatives is the use of bacteriophages. This study was focused on the isolation of bacteriophages that are specific to some of commonly human pathogens namely E. coli, Streptococcus pyogenes, Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella spp. and Klebsiella pneumoniae. These bacteriophages were isolated from sewages that were collected from four different locations in Kirkuk City. Apart from S. pyogenes, bacteriophages specific to all tested bacteria were successfully isolated and tested for their effectiveness by spot test. The most effective

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Publication Date
Mon May 21 2007
Journal Name
Journal Of Planner And Development
Determination of levels of interaction between urban land use and the adoption of spatial analysis techniques (study area, Najaf City)
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Publication Date
Sun Sep 27 2020
Journal Name
Iraqi National Journal Of Nursing Specialties
Effectiveness of an Educational Program on Patients’ Knowledge Concerning care of Vascular Access of Hemodialysis in Al-Muthana Teaching Hospitals
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Objectives:  The study aims to identify the effects of an educational program on patients’ knowledge about vascular access care and to find out the relationship between patients knowledge scores and their selected demographic variable.                                                                                  &

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Publication Date
Wed Jan 01 2025
Journal Name
Baghdad Science Journal
The effect of Bio and Nano Fertilizer on Growth and Yield of Basil Plant and its Content of Active Ingredients
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A factorial experiment was conducted at the College of Education for Pure Sciences Ibn al Haitham/University of Baghdad for the 2023 growing season to study the effect of the biofertilizer represented by the mycorrhizae vaccine and the NPK Nano fertilizer on some indicators of vegetative and root growth, yield, and volatile oil production of the basil plant, Ocimum basilicum L., the experiment included two factors. The rst factor was mycorrhizae inoculum at 2 levels: 0 (no addition) and an addition of 25 g plant–1, as the seeds were inoculated upon planting. The second factor was spraying the plant’s shoots with NPK Nano fertilizer at four levels (0, 0.5, 1, 1.5) g l–1. The results showed a signicant eect of the treatment of inocula

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Publication Date
Wed Jul 08 2015
Journal Name
Ibn Al-haitham J. For Pure & Appl. Sci.
Evaluation of the Efficacy of Arbuscular Mycorrhizal Fungi in Enhancing Resistance of Lycopersicon esculentum Roots Against Fusarium oxysporum Wilt Disease
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The objective of this investigation was to study the effects of amixture of three arbuscular mycorrhizal species : Glomus etunicatum , G. leptotichum and Rhizophagus intraradices on the induced resistance of Lycopersicon esculentum roots infected with Fusarium oxysporum f.sp.lycopersici which is causal agent of wilt in the presence of organic matter peatmose (O). The work was achieved in aplastic house ( Shed) using pot culture planted for 10 weeks. Results indicated significant increase of all mycorrhizal colonization parameters ( F% , M% , m% , a% , A% ) . Highest percentage of mycorrhization was detected in roots infected with the pathogen 4 weeks after mycorrhizal colonization . On the other hand least colonization was shown in the dual

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Publication Date
Sun Jul 02 2006
Journal Name
Journal Of The Faculty Of Medicine Baghdad
a placebo control study of the effect of nigella sativa fixed oil on the healing rate of recurrent aphthous ulceration
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Publication Date
Sun Jan 01 2023
Journal Name
The Egyptian Journal Of Hospital Medicine
Association of Interleukin-12B Polymorphism and Serum Level of Interleukin-12 in a Sample of Iraqi Patients with Rheumatoid Arthritis
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Background In rheumatoid arthritis, your immune system attacks the tissue lining the joints on both sides of your body. Other parts of the body may also be affected. Unsure of the exact cause. Two separate genes termed IL12A (p35) and IL12 encode the heterodimeric cytokine known as IL12 (p40). Several different hematopoietic cell types can have several different hematopoietic cell types that can generate antigen-presenting cells (APCs), including DCs and macrophages. Objectives This study aimed to investigate if the interleukin IL-12B gene's common polymorphisms in an Iraqi population were associated with RA. Material and methods Blood samples were taken from 70 Iraqi patients with RA illnesses and 30 Iraqi controls during the periods from

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