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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
Sat May 01 2021
Journal Name
Journal Of Physics: Conference Series
Investigation and Study of Photonic Current Rate in Bremsstrahlung process
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In this paper, we investigate and study quantum theoretical of quark-gluon interaction modeling in QGP matter formatted. In theoretical modeling, we can use a flavor number, strength coupling, critical energy Tc = 190 MeV, system energy (400-650)MeV, fugacity of quark and gluon, and photon energy in range of 1-10 GeV parameter to calculation and investigation spectrum of photon rate. We calculation and study the photon rate produced through bremsstrahlung processes from the stable QGP matter. The photon rate production from cg → dgy systems at bremsstrahlung processes are found to be increased with increased fugacity, decreased strength coupling, decreased the photons energy and temperature of system. The photons rate in cg → dgy is inc

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Publication Date
Sat Nov 01 2014
Journal Name
Al-khwarizmi Engineering Journal
Experimental and Theoretical Investigation of Impact Dynamic Plasticity for CK45
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Abstract

This paper represents a study of the effect of the soil type, the drilling parameters and the drilling tool properties on the dynamic vibrational behavior of the drilling rig and its assessment in the drilling system. So first, an experimental drilling rig was designed and constructed to embrace the numerical work.

The experimental work included implementation of the drill-string in different types of soil with different properties according to the difference in the grains size, at different rotational speeds (RPM), and different weights on bit (WOB) (Thrust force), in a way that allows establishing the charts that correlate the vibration acceleration, the rate of penetration (ROP), and the power

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Publication Date
Wed Jan 01 2020
Journal Name
Aip Conference Proceedings
Investigation hydraulic performance of splash fills packing in cooling tower
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Heat is one of the most energy forms emitted to atmosphere by industrial processes. Water is considered to be the best material to reduce heat energy since its available in nature in abundance and has the ability to absorb heat efficiently. Cooling towers are ideal alternatives to re-cool hot water instead of throwing it especially in places that lack natural water resources or when there are environmental precautions because water with high temperature would be harmful to the ecosystem when it recycled to natural resources such as rivers and lakes. Also, cooling towers considered economically feasible when using west water. This paper interests with hydraulic characteristics of a counter flow wet cooling tower which was investigated experi

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Publication Date
Fri Jan 01 2021
Journal Name
Chemical Industry And Chemical Engineering Quarterly
Electrochemical harvesting of microalgae꞉ Parametric and cost-effectivity comparative investigation
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The cost of microalgae harvesting constitutes a heavy burden on the commercialization of biofuel production. The present study addressed this problem through economic and parametric comparison of electrochemical harvesting using a sacrificial electrode (aluminum) and a nonsacrificial electrode (graphite). The harvesting efficiency, power consumption, and operation cost were collected as objective variables as a function of applied current and initial pH of the solution. The results indicated that high harvesting efficiency obtained by using aluminum anode is achieved in short electrolysis time. That harvesting efficiency can be enhanced by increasing the applied current or the electrolysis time for both electrode materials, where 98

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Publication Date
Fri May 03 2019
Journal Name
Photonics
Design Investigation of 4 × 4 Nonblocking Hybrid Plasmonic Electrooptic Switch
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This paper proposes a compact, plasmonic-based 4 × 4 nonblocking switch for optical networks. This device uses six 2 × 2 plasmonic Mach-Zehnder switch (MZS), whose arm waveguide is supported by a JRD1 polymer layer as a high electro-optic coefficient material. The 4 × 4 switch is designed in COMSOL environment for 1550 nm wavelength operation. The performance of the proposed switch outperforms those of conventional (nonplasmonic) counterparts. The designed switch yields a compact structure ( 500 × 70   µ m 2 ) having V π L = 12   V · µ m , 1.5 THz optical bandwidth, 7.7 dB insertion loss, and −26.5 dB crosstalk. The capability of the switch to route 8 × 40 Gbps WDM signal is demonstrated successfully.

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Publication Date
Wed Apr 05 2023
Journal Name
Journal Of Engineering
Experimental and Numerical Investigation of Creep Behavior In Isotropic Composites
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Creep testing is an important part of the characterization of composite materials. It is crucial to determine long-term deflection levels and time-to-failure for these advanced materials. The work is carried out to investigate creep behavior on isotropic composite columns. Isotropy property was obtained by making a new type of composite made from a paste of particles of carbon fibers mixed with epoxy resin and E-glass particles mixed with epoxy resin. This type of manufacturing process can be called the compression mold composite or the squeeze mold composite. Experimental work was carried out with changing the fiber concentration (30, 40 and 50% mass fraction), cross section shape, and type of composite. The creep results showed that th

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Publication Date
Wed Jan 01 2020
Journal Name
Iop Conference Series: Materials Science And Engineering
Numerical Investigation of Drag Reduction Techniques in a Car Model
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Abstract<p>Reducing the drag force has become one of the most important concerns in the automotive industry. This study concentrated on reducing drag through use of some external modifications of passive flow control, such as vortex generators, rear under body diffuser slices and a rear wing spoiler. The study was performed at inlet velocity (V=10,20,30,40 m/s) which correspond to an incompressible car model length Reynolds numbers (Re=2.62×10<sup>5</sup>, 5.23×10<sup>5</sup>, 7.85×10<sup>5</sup> and 10.46×10<sup>5</sup>), respectively and we studied their effect on the drag force. We also present a theoretical study finite volume method (FVM) of solvi</p> ... Show More
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Publication Date
Mon Feb 04 2019
Journal Name
Iraqi Journal Of Physics
Experimental investigation of dusty plasma characteristics in AC discharge system
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In the present work, the effect of size of zinc dust particles on
AC argon discharge characteristics are investigated
experimentally. The plasma characteristics are determined by
using optical emission spectroscopy (OES) techniques. The
results illustrated that the electron temperature (Te) in the present
and absent of Zinc dust particle is reduced with increasing of
pressure. The electron temperature decreases with increasing of
Zinc dust size. Excitation temperature Tex is reduces with
increasing of Ar pressure in present and absent of zinc dust
particles. The present of Zinc dust reduce the Tex of Ar in both
Zinc dust size. The electron density increasing in the present and
absent of both zinc dust siz

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Publication Date
Wed Dec 30 2020
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Experimental Investigation of Moisture Sorption Isotherms for Mefenamic Acid Tablets
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   The moisture sorption isotherms of Mefenamic acid tablets were investigated by measuring the experimental equilibrium moisture content (EMC) using the static method of saturated salt solutions at three temperatures (25, 35, and 45°C) and water activity range from 0.056 to 0.8434. The results showed that EMC increased when relative humidity increased and the sorption capacity decreased, the tablets became less hygroscopic and more stable when the temperature increased at constant water activity. The sorption curves had a sigmoid shape, type II according to Brunauer’s classification. The hysteresis effect was significant along with the whole sorption process. The results were fitted to three models: Oswin, Smith, and Guggen

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Publication Date
Mon Aug 01 2011
Journal Name
Journal Of Engineering
NUMERICAL INVESTIGATION OF LAMINAR MIXED CONVECTION IN TROMBE WALL CHANNEL
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The two dimensional steady, combined forced and natural convection in vertical channel is
investigated for laminar regime. To simulate the Trombe wall channel geometry properly, horizontal
inlet and exit segments have been added to the vertical channel. The vertical walls of the channel are
maintained at constant but different temperature while horizontal walls are insulated. A finite
difference method using up-wind differencing for the nonlinear convective terms, and central
differencing for the second order derivatives, is employed to solve the governing differential
equations for the mass, momentum, and energy balances. The solution is obtained for stream
function, vorticity and temperature as dependent variables

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