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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 Dec 01 2012
Journal Name
Journal Of Engineering
Numerical and experimental investigation on the performance of the capillary tube using R-134a and R-600a
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In this paper, isobutane (R-600a) is used as a suitable substitute for (R-134a) when changing the length of capillary tube. And the experimental data on capillary tube are obtained under different conditions such as (subcooling and ambient temperatures) on domestic refrigerator (9ft3 size), this data shows that (R-600a) a suitable substitute for (R134a) .The test presented a model for a steady state, two-phase flow in capillary tube for vapour compression system .The numerical model depends on conservation equations (mass, energy and momentum) as wall as the equation of state for refrigerant. The solution methodology was implemented by using finite difference techniques. The system results indicate that it is possible to change the refri

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Publication Date
Mon Jan 01 2018
Journal Name
Journal Of Global Pharma Technology
Molecular Investigation of Curli Fimbriae Genes in Enterobacter cloacae Isolated from Various Clinical Sources in Baghdad, Iraq
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Thirteen isolates were collected from various clinical sources during the periodfrom 22/10/2017 to 22/12/2017. All the isolates were diagnosed based on the microscopic and biochemical propertiesby Vitek-2 Compact system. All isolates formed biofilm 100%, with 30% of isolatesbiofilm produced strongly and 70% on medium. The results of the present study have shown the presence of Curli fimbriae genes in E. cloacae bacteria from cases of urinary tract infections, infected patient with blood bacteremia and inflammation of wounds. Curli fimbriae is considered to be an important factor in the virulence of E.cloacae bacteria, which plays an important role in adhering and combining cells on solid surfaces to form the biofilmand helps in the adhesion

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Publication Date
Sun Apr 15 2018
Journal Name
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Comparative Experimental and Numerical Investigation on Electrical Discharge Drilling of AISI 304 using Circular and Elliptical Electrodes
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This work introduces a new electrode geometry for making holes with high aspect ratios on AISI 304 using an electrical discharge drilling (EDD) process. In addition to commercially available cylindrical hollow electrodes, an elliptical electrode geometry has been designed, manufactured, and implemented. The principal aim was to improve the removal of debris formed during the erosion process that adversely affects the aspect ratio, dimensional accuracy, and surface integrity. The results were compared and discussed to evaluate the effectiveness of electrode geometry on the machining performance of EDD process with respect to the material removal rate (MRR,) the electrode wear rate (EWR), and the tool wear ratio (TWR). Dimensional features an

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Publication Date
Mon Aug 01 2011
Journal Name
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EXPERIMENTAL INVESTIGATION OF LAMINAR NATURAL CONVECTION HEAT TRANSFER IN A RECTANGULAR ENCLOSURE WITH AND WITHOUT INSIDE PARTITIONS
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Experimental study has been conducted for laminar natural convection heat transfer of air flow through a rectangular enclosure fitted with vertical partition. The partition was oriented parallel to the two vertical isothermal walls with different temperatures, while all the other surfaces of the enclosure were insulated. In this study a test rig has been designed and constructed to allow studying the effect of Rayleigh number, aperture height ratio, partition thickness, the position of aperture according to the side walls and according to the height, the position of the partition according to the hot wall, and partition inclination. The experiments were carried out with air as the working fluid for Rayleigh number range (5*107 – 1.3*10

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Publication Date
Sat Aug 01 2015
Journal Name
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An Investigation into Thermal Performance of Closed Wet Cooling Tower for Use with Chilled Ceilings in Buildings
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Chilled ceilings systems offer potential for overall capital savings. The main aim of the present research is to investigate the thermal performance of the indirect contact closed circuit cooling tower, ICCCCT used with chilled ceiling, to gain a deeper knowledge in this important field of engineering which has been traditionally used in various industrial & HVAC systems. To achieve this study, experimental work were implemented for the ICCCCT use with chilled ceiling. In this study the thermal performances of closed wet cooling tower use with chilled ceiling is experimentally and theoretically investigated. Different experimental tests were conducted by varying the controlling parameters to investigate their effects

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Publication Date
Wed Jul 10 2019
Journal Name
Proceedings Of The Institution Of Mechanical Engineers, Part H: Journal Of Engineering In Medicine
The speed, reflection and intensity of waves propagating in flexible tubes with aneurysm and stenosis: Experimental investigation
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A localized stenosis or aneurysm is a discontinuity that presents the pulse wave produced by the contracting heart with a reflection site. However, neither wave speed ( c) in these discontinuities nor the size of reflection in relation to the size of the discontinuity has been adequately studied before. Therefore, the aim of this work is to study the propagation of waves traversing flexible tubes in the presence of aneurysm and stenosis in vitro. We manufactured different sized four stenosis and four aneurysm silicone sections, connected one at a time to a flexible ‘mother’ tube, at the inlet of which a single semi-sinusoidal wave was generated. Pressure and velocity were measured simultaneously 25 cm downstream the inlet of th

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Publication Date
Fri Nov 26 2021
Journal Name
Nanomaterials
Solidification Enhancement in a Multi-Tube Latent Heat Storage System for Efficient and Economical Production: Effect of Number, Position and Temperature of the Tubes
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Thermal energy storage is an important component in energy units to decrease the gap between energy supply and demand. Free convection and the locations of the tubes carrying the heat-transfer fluid (HTF) have a significant influence on both the energy discharging potential and the buoyancy effect during the solidification mode. In the present study, the impact of the tube position was examined during the discharging process. Liquid-fraction evolution and energy removal rate with thermo-fluid contour profiles were used to examine the performance of the unit. Heat exchanger tubes are proposed with different numbers and positions in the unit for various cases including uniform and non-uniform tubes distribution. The results show that

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Thu Feb 07 2019
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Investigation of Nonlinear Optical Characteristics of the Multi-Wall Carbon Nanotubes (MWCNT's) Suspensions using Nonlinear Self-Diffraction of a Laser Beam
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Nonlinear diffraction patterns can be obtained by focusing a laser beam through a thin slice of the material. Here, we investigated experimentally the formation of the far field nonlinear diffraction patterns of cw laser beam at 532 nm passing through a quartz cuvette containing multi-wall carbon nanotubes (MWCNT's) suspended in acetone and in DI water at concentrations of 0.030.wt.%, 0.045 wt.%, 0.060 wt.%, and 0.075 wt.%. Our results show that increasing the concentration of both types of suspensions (MWCNTs in acetone and MWCNTs DI water) led to increase in the number of pattern rings which indicates an increase in their nonlinear refractive indices. Moreover, MWCNTs DI water suspension at a concentration of 0.075 wt. % was more effic

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Publication Date
Sun Jan 01 2023
Journal Name
Journal Of The Mechanical Behavior Of Materials
Investigation of the performance of integrated intelligent models to predict the roughness of Ti6Al4V end-milled surface with uncoated cutting tool
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Abstract<p>Titanium alloys are broadly used in the medical and aerospace sectors. However, they are categorized within the hard-to-machine alloys ascribed to their higher chemical reactivity and lower thermal conductivity. This aim of this research was to study the impact of the dry-end-milling process with an uncoated tool on the produced surface roughness of Ti6Al4V alloy. This research aims to study the impact of the dry-end milling process with an uncoated tool on the produced surface roughness of Ti6Al4V alloy. Also, it seeks to develop a new hybrid neural model based on the training back propagation neural network (BPNN) with swarm optimization-gravitation search hybrid algorithms (PSO-GS</p> ... Show More
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Publication Date
Tue Oct 01 2013
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Radioelectronics And Communications Systems
BER performance enhancement for secure wireless communication systems based on DCSK-MIMO techniques under Rayleigh fading channel
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There has been a growing interest in the use of chaotic techniques for enabling secure communication in recent years. This need has been motivated by the emergence of a number of wireless services which require the channel to provide very low bit error rates (BER) along with information security. As more and more information is transacted over wireless media, there has been increasing criminal activity directed against such systems. This paper investigates the feasibility of using chaotic communications over Multiple-Input-Multiple-Output (MIMO) channels. We have studied the performance of differential chaos shift keying (DCSK) with 2×2 Alamouti scheme and 2×1 Alamouti scheme for different chaotic maps over additive white Gaussian noise (

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