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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
Thu Dec 01 2016
Journal Name
المجلة العربية للعلوم و نشر الأبحاث
Assessment of Carbonate Rocks , Western Desert of Iraq as Dimension Stones for Building
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Publication Date
Sun Jan 03 2016
Journal Name
Journal Of Educational And Psychological Researches
Professional competencies and teaching university professor from the point of view of students
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Publication Date
Fri Jul 01 2016
Journal Name
Agricultural Engineering
The Change in Spectrum of Drops in the Exploitation Process of Agricultural Nozzles
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Abstract<p>Agricultural nozzles usually produce a different drops size depending on the pressure and the physical condition (work life) of the nozzle besides producing a wide range of the drops spectrum in the spray cloud. In this paper the standard flat fan nozzles were investigated regarding the effect of the working pressure and the nozzle physical condition (new and worn nozzles). The size of drops and the spectrum of drops across the long axis of the spray pattern were examined by using Sympatec GmbH Laser Diffraction. Reducing the working pressure from 3 to 2 and then to 1 caused production of larger drops, also using worn nozzles (especially with lower pressure) changed the drops size whi</p> ... Show More
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Sun Oct 02 2022
Journal Name
Engineering, Technology &amp; Applied Science Research
Reliability Analysis of an Uncertain Single Degree of Freedom System Under Random Excitation
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In practical engineering problems, uncertainty exists not only in external excitations but also in structural parameters. This study investigates the influence of structural geometry, elastic modulus, mass density, and section dimension uncertainty on the stochastic earthquake response of portal frames subjected to random ground motions. The North-South component of the El Centro earthquake in 1940 in California is selected as the ground excitation. Using the power spectral density function, the two-dimensional finite element model of the portal frame’s base motion is modified to account for random ground motions. A probabilistic study of the portal frame structure using stochastic finite elements utilizing Monte Carlo simulation

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Publication Date
Fri Oct 26 2018
Journal Name
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Evaluation of toxicity in rats of Ruta chalepensıs L. extracts Growıng in Iraq
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Evaluate the acute and chronic toxicity of Ruta Chalepensis aerial part aqueous extract used in folk medicine in Iraq in Albino Wistar male and female rats. The study of chronic toxicity at the doses 100, 300 and 600mg/kg body weight in male and female rats for 90 days, recorded no mortality. Treated animals showed a normal weight change compared with control. The parameters of male fertility showed a significant decrease in the weight of testis, epididymis and seminal vesicle as well as a reduction in the number and the motility of spermatozoids at treated groups by the doses 300 and 600 mg/kg body weight compared to control group.

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Sat Feb 21 2026
Journal Name
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THE ROLE OF IRAQI SATELLITE TV TOWARDS A CULTURE OF PROTEST AND REMONSTRATION
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The research dealt with a topic that has been practiced and transmitted news in satellite channels in recent years a lot. That is to say the role of satellite channels in the culture of a protest. In general, this study aims to reach to know the extent of the impact of television, especially the impact of the programs that bear the contents of protest and remonstration on the public; and what can be resulted out of these programs as cognitive, emotional and behavioral effects as a result of the individual's exposure to these programs and their impact from the culture of pretense. In addition to that, the research was interested in explaining the role of Iraqi satellite channels in developing and cultivating such culture; and following up

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Publication Date
Tue Feb 14 2023
Journal Name
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Psychological Stress As A Result of the Spread of the COVID-19 Pandemic
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Publication Date
Mon Jan 01 2024
Journal Name
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Preparation and in-vitro evaluation of Carbopol hydrogel of clobetasol-loaded ethylcellulose microsponges
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: Clobetasol propionate (CP) is a potent corticosteroid used for skin conditions but often causes side effects due its systemic absorption. To improve its solubility and reduce it side effects (like skin irritation, skin atrophy, hypopigmentation and steroidal acne), Microsponge (Msg) has been employed as a unique three-dimensional particle that can encapsulate hydrophilic and lipophilic drugs. This study aims to develop and evaluate CP Msg-loaded hydrogels. Two Clobetasol-loaded ethylcellulose-based Msg formulas were prepared using the quasi-emulsion solvent diffusion method, then they were incorporated into Carbopol hydrogel. Two ratios of Carbopol 940 (1% and 1.5% w/w) were used. The prepared hydrogel were assessed for appearance, pH, dr

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Publication Date
Sat Feb 21 2026
Journal Name
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Background: The aim of the study was to investigate the effect of surface treatments of zirconia (grinding and sandblast with 50μm, 100 μm) on shear bond strength between zirconia core and veneering ceramic. Material and methods: Twenty-eight presintered Y-TZP ceramic specimens (IPS e.max ZirCAD, Ivoclar vivadent) were fabricated and sintered according to manufacturer’s instructions. The core specimens were divided randomly in to 4 groups, group 1: no surface treatment, group2: zirconia specimens were ground with silicon carbide paper up to1200 grit under water cooling, group3: zirconia specimens were ground and sandblast with 100 μm alumina, group 4: zirconia specimens were ground and sandblast with 50 μm alumina. Surfa

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Publication Date
Mon Mar 08 2021
Journal Name
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Synthesis and some of the electrical properties of the polymer Mosul poly Berrol
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Thin films were prepared from poly Berrol way Ketrrukemaaih pole of platinum concentrations both Albaarol and salt in the electrolytic Alastontrel using positive effort of 7 volts on the pole and the electrical wiring of the membrane record

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