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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
Mon Mar 07 2022
Journal Name
Journal Of Educational And Psychological Researches
The Purposes of Thinking in the Light of the Holy Qur’an
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This study aims to explain the purposes of thinking in light of the Holy Qur’an. The study adopted the deductive method by analyzing the meanings of the eighteen thinking verses mentioned in the Holy Qur’an That is by referring to the ancient and contemporary book interpretations and inferring the purposes of thinking from the context of those verses. The study concluded that there are seven main purposes, for thinking in the light of the Holy Qur’an, are understanding the universal regulations, contemplating the social codes, inferring, extracting maxims and meanings from the Qur’anic proverbs, analyzing the situation objectively, balancing between interests and evils, and freeing the mind from the authority of the paranormal. T

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Publication Date
Tue Dec 01 2015
Journal Name
Journal Of Engineering
The Role of Transition of Workforce between Companies in Transferring Technology
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The transition of professionals between different sectors is considered as one of sources of
acquisition of technology and will lead to add the practical experience to them. This experience
depending on different factors like: the scientific degree and practical experience by the
professionals, the technology possessed by the transferor sector, the duration that spent by
experienced in transferor sector, the type of work performed by professional….etc.
The research aims to verify the affect of these factors in technology transfer process.
Research reached that the technology transfer process which is depending on the Iraqi competencies
in work is unsatisfied level between Iraqi organizations because there are dif

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Publication Date
Sat Jun 01 2013
Journal Name
Journal Of The College Of Languages (jcl)
Violation of the Strategies of Conversation in Some English Selected Plays
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The present study analyzes the violation of the strategies of conversation in two English plays namely Richard II and King Lear. The present study tries to achieve the following goals: 1. showing how the strategies of real conversation can be applied to conversation in plays. 2. analyzing how the characters communicate with each other to discover how Shakespeare violates the strategies of conversation in depicting his characters. The study has been conducted on the bases of the following hypotheses:

  1. The strategies of conversation which are derived from the study of natural conversation can be applied to conversation in drama with some modification for dramatic purposes.

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Publication Date
Thu Jun 29 2023
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Evaluation of the Mishrif Formation Using an Advanced Method of Interpretation
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The Mishrif Formation is one of the most important geological formations in Iraq consisting of limestone, marl, and shale layers since it is one of the main oil producing reservoirs in the country, which contain a significant portion of Iraq's oil reserves. The formation has been extensively explored and developed by the Iraqi government and international oil companies, with many oil fields being developed within it. The accurate evaluation of the Mishrif formation is key to the successful exploitation of this field. However, its geological complexity poses significant challenges for oil production, requiring advanced techniques to accurately evaluate its petrophysical properties.

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Publication Date
Sat Aug 01 2015
Journal Name
Journal Of Engineering
Reducing of Manufacturing Lead Time by Implementation of Lean Manufacturing Principles
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Many organizations today are  interesting to implementing lean manufacturing principles  that should enable them to eliminating the wastes to reducing a  manufacturing lead time.  This paper concentrates on  increasing  the competitive level of the company in globalization markets and improving of the productivity by reducing the manufacturing lead time. This will be by using the main tool of lean manufacturing which is value stream mapping (VSM) to identifying all the activities of manufacturing process (value and non-value added activities) to reducing elimination of wastes (non-value added activities) by converting a manufacturing system to pull instead of push by applying some of pull system strategies a

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Publication Date
Mon Jun 19 2023
Journal Name
Journal Of Engineering
The Effect of Hydraulic Accumulator on the Performance of Hydraulic System
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The purpose of this paper is to depict the effect of adding a hydraulic accumulator to a hydraulic system. The experimental work includes using measuring devices with interface to measure the pressure and the vibration of the system directly by computer so as to show the effect of accumulator graphically for real conditions, also the effects of hydraulic accumulator for different applications
have been tested. A simulation analysis of the hydraulic control system using MATLAB.R2010b to study was made to study the stability of the system depending on the transfer function, to estimate the effect of adding the accumulator on stability of the system. A physical simulation test was made for the hydraulic system using MATLAB to show the ef

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Publication Date
Sun Apr 30 2017
Journal Name
Journal Of Engineering
The Effect of Fin Design on Thermal Performance of Heat Sink
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      An experimental and computational study is conducted to analyze the thermal performance of heat sinks and to pick up more profound information in this imperative field in the electronic cooling. One important approach to improve the heat transfer on the air-side of the heat exchanger is to adjust the fin geometry. Experiments are conducted to explore the impact of the changing of diverse operational and geometrical parameters on the heat sink thermal
performance. The working fluid used is air. Operational parameters includes: air Reynolds number (from 23597 to 3848.9) and heat flux (from 3954 to 38357 W/m
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Publication Date
Fri May 31 2019
Journal Name
Journal Of Engineering
Geological Model of the Tight Reservoir (Sadi Reservoir-Southern of Iraq)
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A3D geological model was constructed for Al-Sadi reservoir/ Halfaya Oil Field which is discovered in 1976 and located 35 km from Amara city, southern of Iraq towards the Iraqi/ Iranian borders.

Petrel 2014 was used to build the geological model. This model was created depending on the available information about the reservoir under study such as 2D seismic map, top and bottom of wells, geological data & well log analysis (CPI). However, the reservoir was sub-divided into 132x117x80 grid cells in the X, Y&Z directions respectively, in order to well represent the entire Al-Sadi reservoir.

Well log interpretation (CPI) and core data for the existing 6 wells were the basis of the petrophysical model (

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Publication Date
Thu Feb 01 2018
Journal Name
Journal Of Engineering
Optimization of Cutting Parameters on Delamination of Drilling Glass-Polyester Composites
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This paper attempted to study the effect of cutting parameters (spindle speed and feed rate) on delamination phenomena during the drilling glass-polyester composites. Drilling process was done by CNC machine with 10 mm diameter of high-speed steel (HSS) drill bit. Taguchi technique with L16 orthogonal layout was used to analyze the effective parameters on delamination factor. The optimal experiment was no. 13 with spindle speed 1273 rpm and feed 0.05 mm/rev with minimum delamination factor 1.28.                                       &

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Publication Date
Fri Dec 15 2023
Journal Name
Al-academy
Representations of the Metaverse in the Works of Potter Jason Walker
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The current research studies (representations of metaphysics in the works of potter Jason Walker) a concept that refers to To a large extent, by conveying a sense of reality to the recipient by conveying ideas, contents, and connotations. A variety of center hit, dispersion, and rejection of everything that prevails, so our position on the closed text has shifted To the open text, through the role played by cross-pollination in the works of the potter (Jason Walker), which established a clear hypothetical vision of the image represented in the construction of the ceramic work and the thought that was embodied in that image represented by the nature of its unrealistic formations for those ceramic artworks. It is thus considered a logical

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