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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 Apr 01 2023
Journal Name
Journal Of Medicinal And Chemical Sciences
Investigation of Biofilm Formation and Antibiotic Resistant of Bacteria Isolated from Septic Neonates
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Neonatal sepsis refers to the bacterial bloodstream infections of the newborn during the neonatal period as usually the first twenty-eight days of life. The current study was done in the laboratories of AL-Batool Teaching Hospital for Gynecology and Pediatrics in Baqubah, Diyala Governorate, including 140 blood specimens collected from the neonates admitted to the hospital with suspected sepsis, the ages of the both groups was ranged from 1 day to 28 days. Out of the total cultured samples, 32.14% (45 of 140) were positive and 67.86% (95 of 140) were negative blood culture. 45 of 140 samples were negative to the blood culture chosen as control group. The results showed highest isolates were Coagulase Negative Staphylococcus (CoNS) 19 (42.2%

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Publication Date
Wed Jul 31 2019
Journal Name
Journal Of Engineering
Experimental Investigation of Vibration Stress Relief of A106 Steel Pipe T-Welded Fittings
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This research examines the use of vibratory treatments to reduce residual stresses in small welded parts. In this experimental investigation, a post weld vibration treatment was applied to T- A106 steel pipe fitting specimens to study the effect of the treatment on the residual stress and the hardness of the material. The vibratory stress relief treatment was carried out at different vibration frequency. The results have demonstrated that post-weld vibratory stress relief of small size fittings is possible and residual stress may be relieved, and the treatment may be an alternative method for heat treatment especially when unchange in dimensions and material stability are required.

 

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Tue Jun 14 2005
Journal Name
Iraqi Journal Of Laser
Design and Operation of Mini-TEA CO2 Laser and Investigation of Preionization Effect
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A Mini-TEA CO2 laser system was designed and operated to obtain a pulse at 10.6 μm. Output energy of 30 mJ, with preionization pins, and pulse duration of 100ns were obtained. While an output energy of 6mJ and pulse duration of 100 ns in absence of pre-ionization were obtained. The system was operated with Ernest profile main-discharge electrodes. Dependencies of supply voltage and output laser energy on the pressure inside laser cavity were investigated as well as dependencies of supply voltage and output energy on the main capacitor(8CO2 : 8N2 : 82He :2CO). Efficiency of was calculated to be 4.4%.

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Publication Date
Thu Mar 18 2021
Journal Name
Egyptian Journal Of Chemistry
Investigation of the Influence of Membrane Type on the Performance of Microbial Fuel Cell
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Corrosion Resistance Enhancement for Low Carbon Steel by Gas Phase Coating
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Corrosion Resistance Enhancement for low carbon steel is very important to extend its life service, the coating process is one of the methods which can using to achieve this, and it's the most important in surface treatments to improve the properties of metals and alloys surfaces such as corrosion resistance. In this work, low carbon steel was nitrided and coated with nano zinc using gas phase coating technical, to enhance the resistance of corrosion. The process included adding two layers. The first, a nitride layer, was added by precipitating nitrogen (N) gas, and the second, a zinc (Zn) layer, was added by precipitating Zn. The process of precipitating was carried out at different periods (5, 10, and 15 minutes). Scan electron mi

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Publication Date
Tue May 16 2023
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EXPERIMENTAL INVESTIGATION OF INDIVIDUAL EVACUATED TUBE HEAT PIPE SOLAR WATER HEATING SYSTEMS
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lar water heating systems with heat pipes of three diameter groups of 16, 22 and 28.5 mm. The first and third groups had evaporator lengths of 1150, 1300 and 1550 mm. The second group had an additional length of 1800 mm. all heat pipes were of fixed condenser length of 200 mm. Ethanol at 50% fill charge ratio of the evaporator volume was used as the heat pipes working fluid. Each heat pipe condenser section was inserted in a storage tank and the evaporator section inserted into an evacuated glass tube of the Owens- Illinois type. The combined heat pipe and evacuated glass tube form an active solar collector of a unique design.
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Publication Date
Fri Sep 06 2024
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Optimization photodetection performance: investigation of doping effect on PVA/Y2O3 composite material
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In this work, the photodetection performance of polyvinyl alcohol (PVA) nanofibers and its composite with yttrium oxide (Y2O3) at different concentrations (2.5, 5, 10) wt% are examined deposited on p-type Si with (111) orientation. Electrospinning technique was used to create nanofiber composites. Adding Y2O3 significantly impacts the PVA nanofibers where ultraviolet-visible (UV-Vis) spectroscopy optical absorption energy gap decreases with increased concentration (2.8, 2.6, and 2.3) eV. X-ray diffraction was used to investigate crystal structure, which is cubic structure. The chemical composition study was conducted using Fourier transform infrared spectroscopy (FTIR) spectra, which revealed the stretching vibrations related to the Y-O bon

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Publication Date
Sat Jan 01 2022
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3rd International Scientific Conference Of Alkafeel University (iscku 2021)
Simulation and investigation of the ICP plasma torch’s electrical and thermal properties
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