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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
Tue Jun 21 2022
Journal Name
Journal Of Planner And Development
Knowing the shape of the physical identity of the city
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This  research deals with the form of the physical identity which is concerned with the features and characteristics that distinguish the shape of the city from other existing cities and reveal its similarity with the self (itself) and objective difference with others.  Accordingly, these features must be sophisticated and variable resulting the shape of the city, while preserving the continuity of time, and eventually leads to the emergence of the whole shape. Physical identity is conceptually equivalent with the terms "personality" and "sense of place".  The research determined the criteria for evaluating the physical identity as follows:              

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Publication Date
Tue Sep 01 2015
Journal Name
Journal Of Engineering
Dynamic Analysis of Fluid – Structure Interaction of Axial Fan System
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Fluid-structure interaction method is performed to predict the dynamic characteristics of axial fan system. A fluid-structure interface physical environment method (monolithic method) is used to couple the fluid flow solver with the structural solver. The integration of the three-dimensional Navier-Stokes equations is performed in the time Doman, simultaneously to the integration of the three dimensional structural model. The aerodynamic loads are transfer from the flow to structure and the coupling step is repeated within each time step, until the flow solution and the structural solution have converged to yield a coupled solution of the aeroelastic set of equations. Finite element method is applied to solve numerically

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Publication Date
Thu Jun 29 2017
Journal Name
College Of Islamic Sciences
The prohibition of cheating in the Sunnah of the Prophet
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In The Name of Allah Most Gracious Most Merciful

Cheating is one of the forbidden actions and reprehensible morals that are forbidden by Islamic law, because it involves an assault on rights, whether they are the rights of God Almighty or the rights of God.

people, or self-rights, and because it involves harming others.

Since the Sunnah of the Prophet is the second source of Islamic law, many of the noble hadiths of the Prophet forbid and prohibit cheating.

This study sheds light on it.

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Publication Date
Fri Jun 30 2023
Journal Name
College Of Islamic Sciences
The Role Of Atheism In The Demolition Of Societal Security
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The enemies of religion are still following the approach of undermining the Islamic faith in various ways through the diversity of methods of smear campaigns by raising suspicions to obliterate the Islamic identity and threaten security and stability of social life under the Islamic religion in Islamic societies, as we find that they have employed the doctrine of atheistic thought in order to distance people from the path of truth, distort the features of religion, destabilize psychological security and family stability, and thus destroy societal security by questioning the tolerant faith at times, and by raising suspicions at other times.

Hence, this research came to review the legal duty that requires Islamic scholars to protec

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Publication Date
Sat May 15 2010
Journal Name
International Journal Of Poultry Science
Effect of Dietary Linseed on Egg Quality of Laying Quail
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To assess the effects of dietary oil sources on productive and reproductive traits, sunflower oil, flax oil, corn oil, or fish oil were induced in quail diets. One hundred and sixty-eight 7-week-old Japanese quail were randomly assigned to 4 groups (12 males and 30 females each) with 3 replicates per group containing 4 males and 10 females each and fed for 13 weeks (including one week as an adaptation period) on a commercial diet supplemented with 3% of sunflower oil (T1), flax oil (T2), corn oil (T3), or fish oil (T4). The birds received water and were fed ad libitum during the study. The results of the experiment revealed that dietary supplementation with different sources of oil had no significant effect on male body weight, female body

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Publication Date
Fri Apr 01 2011
Journal Name
Iraqi Journal Of Community Medicine
Anatomical and Histological Features of Placentae of Different Age Groups
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Methods: 112 placentae samples were investigated during the period from August 2007 to August 2008 under light microscopefor mother aged 15 - 45 years old.Results: It was found that normal placental shapes had no correlation to mother age, while abnormal shapes were found more inyoung age groups. The better placental measured parameters were found in mother age 20-24 years. The percentages ofabnormal umbilical cord insertion were very high compared to other studies. Babies’ gender had a correlation with theplacental thickness; male babies have thicker placentae than females. Male babies have longer umbilical cords with widerdiameter than females. Light microscope picture showed the chorionic villi with isolated fetal blood vessel were hig

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Publication Date
Thu Jun 30 2022
Journal Name
Iraqi Geological Journal
Assessment of the Contamination of Baghdad Soils with Lead Element
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The present study aims to study the content and spatial distribution of lead (Pb) contamination in the soils of some Baghdad cities (Middle of Iraq). Twenty soil samples were randomly collected from different land-use in the studied area at a depth between 5 to 30 cm. Ten samples are collected from Al-Rissafa side areas (Adhamiya, Al-Wazeeria (Battery Manufacturer), Shikh Omer, Ziyouna, Karada, Shaab, Sadr city, Al-Za’franiya, Al-Dora expressway, and Alselikh ) and other ten samples are collected from Al-Krakh side areas Al-Dora, Al-Masafi junction, Al-Dora, Sayidia, Al-Salam university college, Al-Bayaa (Industrial District), Jehad, Amirya, Abu Ghraib, Al-hurriya, and Kadhimiya. The soil samples have been analyzed for the lead (P

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Publication Date
Sun May 01 2022
Journal Name
Journal Of Ovonic Research
Effect of antimony on characteristics of HgBa2CaCu2-xSbxO8+δ superconducting
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In this work, HgBa2CaCu2-xSbxO8+δ compounds with (x = 0.2, 0.4, 0.6 and 0.8) have been prepared by the solid-state reaction method. Structural, morphological, and electrical properties were investigated using X-ray diffraction (XRD) and scanning electron microscope (SEM) techniques. Using the 4-probe technique to study the effect of antimony-substitution for Copper on the electrical properties of HgBa2CaCu2-xSbxO8+δ (Hg-1212) phase was investigated by measuring the resistivity as a function of temperature. Results indicate that the addition of antimony (Sb) increases the volume fraction of the phase and changes the superconducting transition temperature Tc of the superconductor to a normal state. The dielectric loss factor and ac

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Publication Date
Tue Jul 11 2023
Journal Name
Journal Of Educational And Psychological Researches
Perceptions of Iraqi EFL Pre-service Teachers of Sustainable Development
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Sustainable development (SD) is an improvement that meets present needs but jeopardizes the ability of new populations to do the same. It is vital to acquaint EFL students with the terminology and idiomatic expressions of this discipline. Nowadays, sustainable development and the environment have been prioritized in every aspect of life. Since culture and the teaching of Foreign language English cannot be separated, the English language becomes the mean of communication in health, economics, education, and politics. Thus, integrating sustainable development goals within language learning and teaching is very important. This descriptive quantitative study aims to investigate the perception of EFL pre-service teachers of sustainable develo

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Publication Date
Mon Feb 15 2021
Journal Name
Systematic Review In Pharmacy
Colorimetric Determination Of Sitagliptin As An Oxidation Derivative Of Ninhydrin
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A sensitive and accurate colorimetric method was developed for the determination of the Sitagliptin phosphate monohydrate, here and after will be named Sitagliptin, in its pure and pharmaceutical form. The suggested approach is based on boosting the sensitivity of the traditional spectrometric methods by derivatizing Sitagliptin into a colored product that absorbs the visible spectrum at 573 nm. The proposed method has effectively improved the sensitivity and the limit of detection for the analysis of Sitagliptin. A linear calibration curve was obtained over the concentration range of 0.1-10 μg/ml with a correlation coefficient of 0.9983. The calculated recovery was within the range of 98.98–100.11%. While the limit of detection LOD and

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