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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 May 09 2024
Journal Name
Polymer Bulletin
Synthesis, characterization and investigation of liquid crystalline properties for some cross-link polymers containing melamine
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In this study, condensation polymerization was used to synthesize a number of novel liquid crystal polymers with 1,3,4-oxadiazole rings based on melamine. The new synthesized polymers were characterized by Fourier transform infrared (FTIR) and proton nuclear magnetic resonance (1HNMR) spectroscopy. Differential scanning calorimetry (DSC) and optical polarization microscopy (OPM) were used to investigate their liquid crystalline properties. The results demonstrated that throughout a wide temperature range, most of the polymers exhibited columnar (CohX) and nematic (N) liquid crystalline phases.

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Publication Date
Sat Jul 28 2018
Journal Name
Journal Of Engineering
Experimental Investigation for the Removal of Toxic Gases from Vehicle Exhaust using Non-Thermal Plasma
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In this study, the use of non-thermal plasma theory to remove toxic gases emitted from a vehicle was experimentally investigated. A non-thermal plasma reactor was constructed in the form of a cylindrical tube made of Pyrex glass. Two stainless steel rods were placed inside the tube to generate electric discharge and plasma condition, by connecting with a high voltage power supply (up to 40 kV). The reactor was used to remove the contaminants of a 1.25-liter 4-cylinder engine at ambient conditions. Several tests have been carried out for a ranging speed from 750 to 4,500 rpm of the engine and varying voltages from 0 to 32 kV. The gases entering the reactor were examined by a gas analyzer and the gases concentration ratio

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Publication Date
Thu May 09 2024
Journal Name
Polymer Bulletin
Synthesis, characterization and investigation of liquid crystalline properties for some cross-link polymers containing melamine
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Publication Date
Thu Nov 01 2018
Journal Name
Journal Of Biological Sciences
Investigation of Plasmid-Associated Fluoroquinolone Resistance in Nosocomial Pseudomonas aeruginosa Isolated from Infected Burn Wounds
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Publication Date
Thu Oct 15 2015
Journal Name
International Journal Of Computer Applications
Experimental Investigation for Small Horizontal Portable Wind Turbine of Different Blades Profiles under Laboratory Conditions
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Experimental investigation for small horizontal portable wind turbine (SHPWT) of NACA-44, BP-44, and NACA-63, BP-63 profiles under laboratory conditions at different wind velocity range of (3.7-5.8 m/s) achieved in present work. Experimental data tabulated for 2, 3, 4, and 6- bladed rotor of both profiles within range of blade pitch angles . A mathematical model formulated and computer Code for MATLAB software developed. The least-squares regression is used to fit experimental data. As the majority of previous works have been presented for large scale wind turbines, the aims were to present the performance of (SHPWT) and also to make a comparisons between both profiles to conclude which is the best performance. The overall efficiency and el

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Publication Date
Mon Mar 29 2021
Journal Name
Eureka: Physics And Engineering
INVESTIGATION ON THE AIR-GAS CHARACTERISTICS OF AIR-HYDROGEN MIXER DESIGNED FOR DUAL FUEL – ENGINES
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High smoke emissions, nitrogen oxide and particulate matter typically produced by diesel engines. Diminishing the exhausted emissions without doing any significant changes in their mechanical configuration is a challenging subject. Thus, adding hydrogen to the traditional fuel would be the best practical choice to ameliorate diesel engines performance and reduce emissions. The air hydrogen mixer is an essential part of converting the diesel engine to work under dual fuel mode (hydrogen-diesel) without any engine modification. In this study, the Air-hydrogen mixer is developed to get a homogenous mixture for hydrogen with air and a stoichiometric air-fuel ratio according to the speed of the engine. The mixer depends on the balance between th

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Publication Date
Sat Jan 01 2022
Journal Name
The 2nd Universitas Lampung International Conference On Science, Technology, And Environment (ulicoste) 2021
Investigation of the vibrational spectral and electronic properties for ZnxBe7-xO7 wurtzoid via DFT approximation
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Publication Date
Fri Jan 01 2021
Journal Name
Journal Of Engineering
A Computational Fluid Dynamics Investigation of using Large-Scale Geometric Roughness Elements in Open Channels
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The hydraulic behavior of the flow can be changed by using large-scale geometric roughness elements in open channels. This change can help in controlling erosions and sedimentations along the mainstream of the channel. Roughness elements can be large stone or concrete blocks placed at the channel's bed to impose more resistance in the bed. The geometry of the roughness elements, numbers used, and configuration are parameters that can affect the flow's hydraulic characteristics. In this paper, velocity distribution along the flume was theoretically investigated using a series of tests of T-shape roughness elements, fixed height, arranged in three different configurations, differ in the number of lines of roughness element

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Publication Date
Mon Jan 02 2017
Journal Name
Al-nahrain Journal For Engineering Sciences (njes)
Experimental Investigation of Forced Convection Heat Transfer and Pressure Drop in Open Cell Aluminum Fins
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Publication Date
Fri May 01 2020
Journal Name
Journal Of Engineering
Chemical and Thermal Investigation on Stability of Tanuma Formation Using Different Additives with Drilling Fluids
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Wellbore stability is considered as one of the most challenges during drilling wells due to the
reactivity of shale with drilling fluids. During drilling wells in North Rumaila, Tanuma shale is
represented as one of the most abnormal formations. Sloughing, caving, and cementing problems
as a result of the drilling fluid interaction with the formation are considered as the most important
problem during drilling wells. In this study, an attempt to solve this problem was done, by
improving the shale stability by adding additives to the drilling fluid. Water-based mud (WBM)
and polymer mud were used with different additives. Three concentrations 0.5, 1, 5 and 10 wt. %
for five types of additives (CaCl2, NaCl, Na2S

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