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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 Mar 01 2009
Journal Name
Baghdad Science Journal
Investigation of the Porosity of Certain Iraqi Clay Deposits by Mercury Porosimeter
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Pore volume, pore diameter, and pore volume distribution of three of Iraqi natural clay deposites were measured using mercury intrusion porosimetry .The clays are white kaolin, colored kaolin, and bentonite .The results showed that the variation of the pore area of the clay deposites followed the following order :- Coloured Kaolin > White Kaolin > Bentonite While the pore volume may be arranged as in the following sequence:- White Kaolin > Coloured Kaolin >Bentonite Also , Bentonite exhibits the narrow range pore size distribution than the white and coloured kaolin.

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Publication Date
Mon Jan 01 2018
Journal Name
Ibn Al-haitham Journal For Pure And Applied Science
Investigation of the Structural, Optical and Electrical Properties of AgInSe2 Thin Films
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Publication Date
Wed Jun 01 2022
Journal Name
Journal Of Engineering
Numerical Investigation of Aerodynamic Characteristics of Supercritical RAE2822 Airfoil with Gurney Flap
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Gurney flap (GF) is well-known as one of the most attractive plain flaps because of the simple configuration and effectiveness in improving the lift of the airfoil. Many studies were conducted, but the effects of GF on the various airfoil types need to be further investigated. This study aimed to clarify the effect of GF in the case of the supercritical airfoil RAE2822. This research includes a steady, two-dimensional computational investigation carried out on the supercritical airfoil type RAE-2822 to analyze Gurney flap (GF) effects on the aerodynamic characteristics of this type of airfoil utilizing the Spalart-Allmaras turbulence model within the commercial software Fluent. The airfoil with the Gurney flap was analyz

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Publication Date
Mon May 14 2018
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Investigation of the Structural, Optical and Electrical Properties of AgInSe2 Thin Films
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  The Silver1Indium1Selenide (AgInSe2) (AIS) thin1films of (3001±20) nm thickness  have been1prepared2from the compound alloys2using thermal evaporation2 technique onto the glass2substrate at room temperature, with a deposition rate2(3±0.1) nm2sec-1.

The2structural, optical and electrical3properties have been studied3at different annealing3temperatures (Ta=450, 550 and 650) K.

The amount3or (concentration) of the elements3(Ag, In, Se) in the  prepared alloy3was verified using  an

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Publication Date
Mon Mar 01 2021
Journal Name
Iraqi Journal Of Physics
Investigation of Structural, Mechanical, Thermal and Optical Properties of Cu Doped TiO2
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In this work, Pure and Cu: doped titanium dioxide nano-powder was prepared through a solid-state method. the dopant concentration [Cu/TiO2 in atomic percentage (wt%)] is derived from 0 to 7 wt.%. structural properties of the samples performed with XRD revealed all nanopowders are of titanium dioxide having polycrystalline nature. Physical and Morphological studies were conducted using a scanning electronic microscope SEM test instrument to confirm the grain size and texture. The other properties of samples were examined using an optical microscope, Lee's Disc, Shore D hardness instrument, Fourier-transform infrared spectroscopy (FTIR), and Energy-dispersive X-ray spectroscopy (EDX). Results showed that the thermal conductivity

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Publication Date
Tue Jul 02 2019
Journal Name
Fibers
Experimental Investigation of the Behavior of Self-Form Segmental Concrete Masonry Arches
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This research aims to introduce a new technique-off-site and self-form segmental concrete masonry arches fabrication, without the need of construction formwork or centering. The innovative construction method in the current study encompasses two construction materials forms the self-form masonry arches, wedge-shape plain concrete voussoirs, and carbon fiber-reinforced polymer (CFRP) composites. The employment of CFRP fabrics was for two main reasons: bonding the voussoirs and forming the masonry arches. In addition, CFRP proved to be efficient for strengthening the extrados of the arch rings under service loadings. An experimental test was conducted on four sophisticated masonry arch specimens. The research parameters were the Keystone thic

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Publication Date
Wed May 03 2017
Journal Name
Petroleum Science And Technology
Investigation of non-Newtonian flow characterization and rheology of heavy crude oil
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Publication Date
Thu May 18 2023
Journal Name
Journal Of Engineering
Theoritical and Experimental Investigation of the Dynamical Behaviour of Complex Configuration Rotors
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The present work considers an alternative solution for a complex configuration of rotor discs by applying Galerkin Method. The theoretical model consists of elastic shaft carrying number of discs and supported on number of journal bearings. The equation of motion was discretized to finite degree of freedom in terms of the system generalized coordinates. The various effects of the dynamical forces and moments arising from the bearing, discs and shaft were included. Rayleigh beam model is used for analyzing the shaft while the discs are considered rigid . The validity and convergence of the present analysis was carefully checked by comparing with the Finite Element solution. An example of rotor consists of three different size discs and su

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Publication Date
Wed May 17 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Investigation of the Projector Properties of the Magnetic lenses Using Analytical Function
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 A computational investigation has been carried out to describe synthesis optimization procedure of magnetic lenses. The research is concentrated on the determination of the inverse design of the symmetrical double polepiece magnetic lenses whose magnetic field distribution is already defined. Magnetic lenses field model well known in electron optics have been used as the axial magnetic field distribution. This field has been studied when the halfwidth is variable and the maximum magnetic flux density is kept constant. The importance of this research lies in the possibility of using the present synthesis optimization procedure for finding the polepieces design of symmetrical double polepiece magnetic lenses which have the best proje

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Publication Date
Sun Oct 03 2021
Journal Name
Journal Of Interdisciplinary Mathematics
Application of topological concepts to the investigation of COVID-19 (modified) symptoms
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We examine 10 hypothetical patients suffering from some of the symptoms of COVID 19 (modified) using topological concepts on topological spaces created from equality and similarity interactions and our information system. This is determined by the degree of accuracy obtained by weighing the value of the lower and upper figures. In practice, this approach has become clearer.

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