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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
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Effect of crude extracts of the plant local wolf riding in the growth of some fungi
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Make a search on the vegetative parts of the plant local horse guilt of some elements in the Haj Omran area in northern Iraq has included recognition of certain nutrients

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Publication Date
Tue Mar 30 2010
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
The Effect of Operating Conditions of Urea Dewaxing on the Pour Point of Light Lubricating Oil
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An investigation was conducted for dewaxing of lubricating oil fraction by urea to reduce the pour point.In this study mixture of 45 % methyl ethyl ketone (MEK) and 55 % toluene was used as a solvent. The studied variables are mixing time (10-70 min), solvent to oil volume ratio (0.5:1- 2:1), urea to wax weight ratio (2- 6) and constant mixing speed 1500 rpm. By analysis of the experimental results, the best operating conditions achieved are mixing time 40 min, solvent/oil 2:1 volume ratio, and urea/wax 4:1 weight ratio. At these conditions the pour point of the lubricating oil decreases from 24 ° C to -13 °C.

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Publication Date
Sat May 30 2020
Journal Name
Neuroquantology Journal
The Effect of Re-Use of Lossy JPEG Compression Algorithm on the Quality of Satellite Image
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In this study, an analysis of re-using the JPEG lossy algorithm on the quality of satellite imagery is presented. The standard JPEG compression algorithm is adopted and applied using Irfan view program, the rang of JPEG quality that used is 50-100.Depending on the calculated satellite image quality variation, the maximum number of the re-use of the JPEG lossy algorithm adopted in this study is 50 times. The image quality degradation to the JPEG quality factor and the number of re-use of the JPEG algorithm to store the satellite image is analyzed.

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Publication Date
Sun Feb 01 2015
Journal Name
Journal Of Engineering
Effect of Saturation of Sandy Soil on the Displacement Amplitude of Soil Foundation System under Vibration
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In this study, the response and behavior of machine foundations resting on dry and saturated sand was investigated experimentally. A physical model was manufactured to simulate steady state harmonic load at different operating frequencies. The effect of relative density, depth of embedment, foundation area as well as the imposed harmonic load was investigated. It was found that the amplitude of displacement of the foundation increases with increasing the amplitude of dynamic force and operating frequency meanwhile it decreases with increasing the relative density of sand, degree of saturation, depth of embedment and contact area of footing. The maximum displacement was noticed at 33.34 to 41.67 Hz. The maximum displacement amplitude respons

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Publication Date
Sat Dec 01 2018
Journal Name
Al-khwarizmi Engineering Journal
The Influence of Alkaline Treatment of Recycled Natural Materials on the Properties of Epoxy Resin Composites
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Natural fibers and particles reinforced composites are being broadly used due to their bio and specific properties such as low density and easy to machine and production with low cost. In this work, water absorption and mechanical properties such as tensile strength, flexural strength and impact strength of recycled jute fibers reinforced epoxy resin were enhanced by treating these fibers with alkaline solution. The recycled jute fibers were treated with different concentration of (NaOH) solution at (25 0C) for a period of (24) hours. From the obtained results, it was found that all these properties are improved when fibers treated with (7.5wt% NaOH) related to untreated fibers. Conversely, the mentioned properties of composit

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Publication Date
Sun Jan 01 2023
Journal Name
مجلة ميسان للدراسات الأكاديمية
Enhancing Photostability Of Maxillofacial Silicone By The Addition Of Ultraviolet Absorbing Bisoctrizole:, A Review Of Literature
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Publication Date
Wed Jun 14 2023
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Representations of the event in the drawings of the civilizations of the ancient world (selected models)
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This research is concerned with studying the representations of the event in the drawings of the ancient civilizations of the world, and the research consists of two axes, the axis of the theoretical framework, which included (the research problem, its aim, its limits, and the definition of its terminology).
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Publication Date
Thu Jun 30 2011
Journal Name
Al-kindy College Medical Journal
Effect of war on treatment of pulmonary tuberculosis, and evaluation of Directly-observed therapy in Baghdad
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Background: Directly observed therapy-short course (DOTS) had been adopted by World Health Organization (WHO) as hopeful strategy for treatment of tuberculosis (TB) since early nineties. Iraqi health authorities started DOTS implementation since 2001 in Baghdad. Coverage expanded gradually till 100% in 2004. War and unstable security condition hit Iraq since March 2003. Objective: The objective of this study was To evaluate the DOTS implementation program in Baghdad in different periods including 2 unstable periods for proper assessment of war and instability on treatment of TB. Patients and methods: This study had been conducted in Baghdad during four different periods (before and during 2003 war, after war; without and with DOTS). Dire

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Publication Date
Sat Jan 01 2022
Journal Name
Iraqi Journal Of Science
Determination of Magnitudes and Orientation of the Paleostress of Bekhme Structure in Shaqlawa area, Northerneastern Iraq
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This study presents determination of the paleostress magnitudes and orientation of Bekhme Structure in Shaqlawa area northeastern Iraq. Paleostress Analysis of slip-fault measurements is performed using Right dihedral, Lisle diagram and Mohr Circles methods. Depending on Mohr Circles, Bott law and vertical thickness, the magnitudes of the paleostress at the time of the tectonic activity were determined. Firstly, Georient Software was used to estimate the orientation of the paleostresses (σ1, σ2 and σ3). Secondly, using the rupture –friction law, taking into account depth of the overburden and the vertical stress (σv) was calculated to determine the magnitude of the paleostresses (σ1=4500 bars, σ2=1

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Publication Date
Mon Feb 14 2022
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The Educational dimensions of children's television programs in the light of the universal rights of child
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The research aims at determining the type of educational dimensions to be broadcasted in children's television programs, clarifying the technical forms used in children's TV programs, analyzing the educational dimensions provided by children's television programs, and studying the educational dimensions of children's television programs. The researcher used a sample of children's programs: all of us heroes, which is a daily program on the mbc3 channel as well as the program of Tel flowers on the Algerian channel. The researcher designed an analysis content form included categories of analysis. Spss program was used to process the collected data. The research reached several results; the concentration of educational dimensions in

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