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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
Wed Mar 13 2019
Journal Name
Al-khwarizmi Engineering Journal
Investigation Microwave Furnace Effects on Mechanical Properties and Fatigue Life of AA 7075-T73 with Dry and Acid Treatments
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Microwave heating is caused by the ability of the materials to absorb microwave energy and convert it to heat. The aim of this study is to know the difference that will occur when heat treating the high strength aluminum alloys AA7075-T73 in a microwave furnace within different mediums (dry and acidic solution) at different times (30 and 60) minutes, on mechanical properties and fatigue life. The experimental results of microwave furnace heat energy showed that there were variations in the mechanical properties (ultimate stress, yielding stress, fatigue strength, fatigue life and hardness) with the variation in mediums and duration times when compared with samples without treatment. The ultimate stress, yielding stress and fatigue streng

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Publication Date
Fri Dec 01 2023
Journal Name
Baghdad Science Journal
Numerical Investigation of Physical Parameters in Cardiac Vessels as a New Medical Support Science for Complex Blood Flow Characteristics
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This study proposes a mathematical approach and numerical experiment for a simple solution of cardiac blood flow to the heart's blood vessels. A mathematical model of human blood flow through arterial branches was studied and calculated using the Navier-Stokes partial differential equation with finite element analysis (FEA) approach. Furthermore, FEA is applied to the steady flow of two-dimensional viscous liquids through different geometries. The validity of the computational method is determined by comparing numerical experiments with the results of the analysis of different functions. Numerical analysis showed that the highest blood flow velocity of 1.22 cm/s occurred in the center of the vessel which tends to be laminar and is influe

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Publication Date
Wed Jun 01 2016
Journal Name
Journal Of Engineering
Investigation the Optimum Combined Dosages of Date Seeds Powder as Natural Coagulant with Chemical Coagulants in Domestic Wastewater Pretreatment
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The pretreatment process can be considered one of the important processes in wastewater treatment, especially coagulation process to decrease the strength of many pollutants. This paper focused on using powdered date seeds as natural coagulant in addition to chemical coagulants (alum and ferric chloride) to find the optimum dosage of each coagulant that makes efficient removal of turbidity and chemical oxygen demand (COD) from domestic wastewater as a pretreatment process, then finding the optimum combined dosages of date seeds with alum, date seeds with ferric chloride that make efficient removal for both pollutants. Concerning turbidity, the optimum dosage for date seeds, alum and ferric chloride were 40 mg/l (79%), 70

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Publication Date
Tue May 27 2025
Journal Name
Bulletin Of The Chemical Society Of Ethiopia
Preparation, kinetics, and thermodynamic investigation of Janus green dye removal from aqueous solutions using MnO2 nanoparticles as an adsorbent
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In this study, manganese dioxide (MnO₂) nanoparticles (NPs) were synthesized via the hydrothermal method and utilized for the adsorption of Janus green dye (JG) from aqueous solutions. The effects of MnO₂ NPs on kinetics and diffusion were also analyzed. The synthesized NPs were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), energy-dispersive X-ray analysis (EDX), and Fourier-transform infrared spectroscopy (FT-IR), with XRD confirming the nanoparticle size of 6.23 nm. The adsorption kinetics were investigated using three models: pseudo-first-order (PFO), pseudo-second-order (PSO), and the intraparticle diffusion model. The PSO model provided the best fit (R² = 0.999), indicating that the adsorpti

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Publication Date
Wed Jan 01 2020
Journal Name
Euromediterranean Biomedical Journal
ESCHERICHIA COLI O157: H7 INVESTIGATION IN CHILDREN WITH DIARRHEA: AN IRAQI CROSS-SECTIONAL STUDY
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NA Nasir, SHM Ali, HQMA AL-Ess, WA Hussein, MKW Al-Janabi, KIA Mohammed, JM Mosa, Euromediterranean Biomedical Journal, 2020

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Phytochemical Investigation for the Main Active Constituents in Arctium lappa L. Cultivated in Iraq
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Burdock ( Arctium lappa), is among the most popular plants in traditional medicine and it is associated with several biological effects. Literature survey revealed the presence of phenylpropanoid compounds .The most widespread are hydroxycinnamic acids ( mainly caffeic acid and chlorogenic acid) and lignans (mainly arctiin and arctigenin). This work will confirm the presence of these compounds in Arctium lappa, cultivated in Iraq, in both root and leaf samples.  The dried plant samples were extracted by soxhlet with 80% methanol then separated the main constituents by thin layer chromatography (TLC) and high performance liquid  chromatography (HPLC). Identification of the isolated compounds wa

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Publication Date
Sun Mar 01 2015
Journal Name
Journal Of Engineering
Finite Element Investigation on Shear Lag in Composite Concrete-Steel Beams with Web Openings
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In this paper, effective slab width for the composite beams is investigated with special emphasis on the effect of web openings. A three dimensional finite element analysis, by using finite element code ANSYS, is employed to investigate shear lag phenomenon and the resulting effective slab width adopted in the classical T-beam approach. According to case studies and comparison with limitations and rules stipulated by different standards and codes of practice it is found that web openings presence and panel proportion are the most critical factors affecting effective slab width, whereas concrete slab thickness and steel beam depth are less significant. The presence of web opening reduces effective slab width by about 21%.

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Publication Date
Thu Nov 01 2018
Journal Name
Curtin University
Gas hydrates investigation: flow assurance for gas production and effects on hydrate-bearing sediments
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This thesis was aimed to study gas hydrates in terms of their equilibrium conditions in bulk and their effects on sedimentary rocks. The hydrate equilibrium measurements for different gas mixtures containing CH4, CO2 and N2 were determined experimentally using the PVT sapphire cell equipment. We imaged CO2 hydrate distribution in sandstone, and investigated the hydrate morphology and cluster characteristics via μCT. Moreover, the effect of hydrate formation on the P-wave velocities of sandstone was investigated experimentally.

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Publication Date
Mon Jan 01 2018
Journal Name
Matec Web Of Conferences
Investigation of surface area of lakes and marshes from satellite images by using remote sensing and geographic information system integration in Iraq
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Water level and distribution is very essential in almost all life aspects. Natural and artificial lakes represent a large percentage of these water bodies in Iraq. In this research the changes in water levels are observed by calculating the areas of five different lakes in five different regions and two different marshes in two different regions of the country, in a period of 12 years (2001 - 2012), archived remotely sensed images were used to determine surface areas around lakes and marshes in Iraq for the chosen years . Level of the lakes corresponding to satellite determined surface areas were retrieved from remotely sensed data .These data were collected to give explanations on lake level and surface area fluctuations. It is imp

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Publication Date
Sun Mar 06 2016
Journal Name
Baghdad Science Journal
Investigation of the dielectric Properties of (PPAB) terminated by phenylenediamine doped by Na2[Fe(CN)5.NO].2H2O using Lumped equivalent circuit
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The aim of this paper is to demonstrate the effect of Na2[Fe(CN)5.NO].2H2O impurity (0.1 M) concentration on the dielectrical properties of poly (P-Aminobenzaldehyde) terminated by pheneylenediamine in the frequency and temperature ranges (1-100)KHz and (283-348) K respectively.These properties include dissipation factor, series and parallel resistance, series and parallel capacitance, real and imaginary part of the dielectric constant, a.c conductivity and impedance (real and imaginary) part, that have been deduced from equivalent circuit. The investigation shows that adding Na2[Fe(CN)5.NO].2H2O as additive to the polymer lead to increase of the dielectric constant with increasing temperature and it is decreasing with increasing the freq

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