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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 Jun 01 2014
Journal Name
Baghdad Science Journal
Study of the Inter-Particle Expectation Values for Inter and Outer Shell: Khalil H. Al-Bayati|Ban H. Al-Asaad|Baidaa S. H.
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In this research the Inter-Particle Expectation Values have been studied for atomics Helium (He) and Beryllium (Be) also for He-like ions, Be-like ions (Li-1, B+1? Li+1, Be+2, B+3) by using Hartree-Fock wave functions, We compared the results to some ions which have the same atomic number from each group with atomic number, We compared the results with published calculations to the last studied .

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Publication Date
Sat May 01 2021
Journal Name
Journal Of Physics: Conference Series
Violet Laser Irradiation Effect on The Optical Properties of Cobalt oxide (CoO<sub>2</sub>) Thin Films deposited via Semi-Computerized Spraying System
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Abstract<p>The existing investigation explains the consequence of irradiation of violet laser on the optic properties of (CoO<sub>2</sub>) films. The film was equipped by the utilization of semi-computerized spray pyrolysis technique (SCSPT), it is the first time that this technique is used in the preparation and irradiation using a laser in this technique. From the XRD analysis, the crystalline existence with trigonal crystal system was when the received films were processed by continuous violet laser (405 nm) with power (1W) for different laser irradiation time using different number of times a laser scan (0, 6, 9, 12, 15 and 18 times) with total irradiation time(0,30,45,60,75,90 min</p> ... Show More
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Publication Date
Wed Dec 30 2020
Journal Name
Journal Of Planner And Development
The proportionality of decision taken to sign the AL-Ayadi residential investment project within the Hittin neighborhood in Baghdad by Urban filling style
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This research will deal in a simple way with the concept of urban expansion and taking the decision to sign the spatial signature of residential investment projects in order to reach through them in a real way to the extent of the proportionality of the decision taken, in light of the fulfillment of the conditions that must be met in the matter of making the decision of the spatial signature of the residential investment project and the extent of commitment to them, in which the conditions are: (Ease of access to services and transportation, adequacy of services, commitment to urban land uses) when establishing the investment project represented by the Al-Ayad residential project in the Hittin neighborhood of Al

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Publication Date
Mon Dec 13 2021
Journal Name
International Journal Of Reproductive Biomedicine (ijrm)
Differences in perinatal outcomes in teenage mothers with their first and third pregnancies and predictors of adverse neonatal events: A cross-sectional study
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Background: Repeated teenage pregnancy is a major burden on the healthcare system worldwide. Objective: We aimed to compare teenagers with their first and third pregnancies and to evaluate the likelihood of neonatal complications. Materials and Methods: This cross-sectional study was performed on female teenagers (aged ≤ 19 yr) with singleton pregnancies. The subjects (n = 298) were screened over 12 months. Ninety-six women were excluded, based on the exclusion criteria. The remaining subjects (n = 202) were divided into two groups: teenagers with first pregnancy (n = 96) and teenagers with third pregnancy (n = 47). The subjects were observed throughout pregnancy and delivery. The final sample size of the first and thi

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Publication Date
Sat Jun 04 2022
Journal Name
Journal Of Inorganic And Organometallic Polymers And Materials
Improving the Mechanical Properties, Roughness, Thermal Stability, and Contact Angle of the Acrylic Polymer by Graphene and Carbon Fiber Doping for Waterproof Coatings
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Publication Date
Tue Sep 01 2020
Journal Name
Baghdad Science Journal
Uptake of Three Pharmaceuticals by Beans (Phaseolus vulgaris L.) from Contaminated Soils: امتصاص ثلاثة انواع من الادوية بواسطة نبات الفاصولياء في التربة الملوثة
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The ability of beans (Phaseolus vulgaris L.) to uptake three pharmaceuticals (diclofenac, mefenamic acid and metronidazole) from two types of soil (clay and sandy soil) was investigated in this study to explore the human exposure to these pharmaceuticals via the consumption of beans. A pot experiment was conducted with beans plants which were grown in two types of soil for six weeks under controlled conditions. During the experiment period, the soil pore water was collected weekly and the concentrations of the test compounds in soil pore water as well as in plant organs (roots, stems and leaves) were weekly determined.
The results showed that the studied pharmaceuticals were detected in all plant tissues; their concentration

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Publication Date
Wed Feb 27 2019
Journal Name
Journal Of Nano Research
A Specific NH&lt;sub&gt;3&lt;/sub&gt; Gas Sensor of a Thick MWCNTs-OH Network for Detection at Room Temperature
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NH3 gas sensor was fabricated based on deposited of Functionalized Multi-Walled Carbon Nanotubes (MWCNTs-OH) suspension on filter paper substrates using suspension filtration method. The structural, morphological and optical properties of the MWCNTs film were characterized by XRD, AFM and FTIR techniques. XRD measurement confirmed that the structure of MWCNTs is not affected by the preparation method. The AFM images reflected highly ordered network in the form of a mat. The functional groups and types of bonding have appeared in the FTIR spectra. The fingerprint (C-C stretch) of MWCNTs appears in 1365 cm-1, and the backbone of CNTs observed at 1645 cm-1. A homemade sensi

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Publication Date
Sat Aug 09 2025
Journal Name
Oxidation Communications
SYNTHESIS AND SPECTRAL CHARACTERISATION, MOLECULAR DOCKING, AND ANTIOXIDANT ACTIVITIES OF NOVEL METAL COMPLEXES AND THEIR NANOCOMPLEXES DERIVED FROM AN ISATIN-BASED SCHIFF BASE
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Publication Date
Wed Oct 02 2024
Journal Name
Journal Of International Crisis And Risk Communication Research
Manufacturing Consent: A Critical Discourse Analysis of Benjamin Netanyahu's Speech to the United States Congress in 2024” has been accepted for publication in
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In this paper, the researchers investigate Prime Minister Benjamin Netanyahu's speech before a joint session of the US Congress on July 25, 2024. The researchers primarily aim at highlighting the ideology behind Netanyahu's speech by using qualitative research through the application of critical discourse analysis (CDA), which is employed here in in order to show how certain linguistic choices can manipulate and determine concepts related to power and ideology. The CDA method used is Discourse Historical Approach with the main focus on argumentation management through discursive strategies. The researchers adopt DHA by Wodak (2009) with focusing on the taxonomy of social actor representation by Van Leeuwen (2008). The study reveals th

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Publication Date
Wed Dec 01 2021
Journal Name
Journal Of Economics And Administrative Sciences
Comparison Between Nelson-Olson Method and Two-Stage Limited Dependent Variables (2SLDV ) Method for the Estimation of a Simultaneous Equations System (Tobit Model)
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This study relates to  the estimation of  a simultaneous equations system for the Tobit model where the dependent variables  ( )  are limited, and this will affect the method to choose the good estimator. So, we will use new estimations methods  different from the classical methods, which if used in such a case, will produce biased and inconsistent estimators which is (Nelson-Olson) method  and  Two- Stage limited dependent variables(2SLDV) method  to get of estimators that hold characteristics the good estimator .

That is , parameters will be estim

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