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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
Sun Dec 27 2020
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The role of International Monetary Fund in Planning monetary policy for Developing the Iraqi economy: An Applied Research for the Period (2004-2013)
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The developing countries, like our country Iraq suffer from deep comprehensive structural crisis, manifestations and a clear imbalance between the demand and the supply sides. The overall imbalance in the external balance. As a consequence, this caused the accumulation of foreign debts or failure in the implementation of economic development programs. The countries which are forced to resort to the International Monitoring Funds, and the World Bank for assistance and to express an opinion on policies that include restrictions controls that belong to the monetary, and fiscal side group, imposed on the economies crisis, as a condition for returning to normal which called reform programs. The organize of the events of radical changes in the

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Publication Date
Tue Jan 01 2013
Journal Name
Innovative Systems Design And Engineering
Water And Alcohol Extraction Of Thyme Plant (Thymus Vulgaris) And Activity Study Against Bacteria, Tumors And Used As Anti-Oxidant In Margarine Manufacture
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Isolation had been done for active substances from Thyme plant (Thymus Vulgaris) such as volatile oils, Saponins and Tannins. The percentage in form was (21.1%),(59.2%),( 9.7%) respectively. Also a study of anti-bacterial activity of extracts from Thyme using two types of pathogenic bacteria Escherichia Coli and aurous Staphylococcus showed the ability of inhibition for all different extracts by vary inhibition diameters for different active substances, concentrations and bacteria. One type of cancer cellular line used to study the effect of Thyme extracts on the growth of cells in the laboratory and thus know the specifications of extracts as anti-tumor, (L20B) cell line have been used which is mice Transformed cell Line. The possibility o

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Publication Date
Wed Jun 28 2023
Journal Name
Al–bahith Al–a'alami
The Role of Television News Headlines in Attracting Viewers to News Bulletins: A Field Study from 01/01/2023 to 31/03/2023
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The objective of this study is to ascertain the pivotal role of headlines in captivating viewers' attention toward news bulletins. Additionally, it aims to explore the factors that contribute to the correlation between headlines and the public's acceptance or rejection of the meticulously crafted news articles presented through these bulletins. The study delves into the mechanisms employed in writing and editing headlines, focusing on their style, expert composition, and intriguing nature. These factors inevitably influence the level of acceptance and engagement of the viewership with the news articles disseminated via the news bulletins. Employing a descriptive methodology, the researcher distributed 200 question

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Publication Date
Thu Apr 01 2021
Journal Name
Journal Of Molecular Structure
Mixed-ligand complexes of ampicillin derived Schiff base ligand and Nicotinamide: Synthesis, physico-chemical studies, DFT calculation, antibacterial study and molecular docking analysis
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A novel series of mixed-ligand complexes of the type, [ML1(L2)3]Clx [M= Cr(III), Fe(III), Co(II),Ni(II), Cu(II), Cd(II) and Hg(II), n = 2, 3], was synthesized using Schiff base (HL1) as main ligand, nicotinamide (L2) as secondary ligand, and the corresponding metal ions in 1:3:1 molar ratio. The main ligand, HL1 was prepared by the interaction of ampicillin drug and 4-chlorobenzophenone. The synthesized mixed ligand complexes were characterized by elemental analysis, UV-Vis, FT-IR,1H-NMR,13C-NMR and TG/DTG studies. In the mixed-ligand complexes, the Schiff base ligand, HL1 showed coordination to the central metal ion in tridentate manner via azomethine nitrogen, β-lactam ring oxygen and deprotonated carboxylic oxygen atoms, whereas the sec

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Publication Date
Thu Dec 30 2021
Journal Name
College Of Islamic Sciences
The omission of letters according to Zakaria al-Ansari in his book (Fath al-Rahman by revealing what is ambiguous in the Qur’an)
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Summary

The book (Fatah al-Rahman reveals what is ambiguous in the Qur’an), which is a book of verbal similarities that tries to touch the Qur’an expression, and the subtle differences between its expressions and expressions. It appeared when it appeared in many chapters, from which I chose to delete in monolithic letters such as Ba and Ta, and to heal and delete in non-monosymbols such as (that) and (may) and (no), so the search came to two chapters The first is for deleting the monolithic letters, and the second is for deleting non-monosyllabic letters, preceded by introductory discussions revolving around the linguistic and idiomatic definition of deletion, a brief translation of the

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Publication Date
Wed Dec 11 2019
Journal Name
Journal Of The College Of Education For Women
The Impact of the Quranic Readings in Removing the Paradox in Imam Al Wahidi in his Al Wasiet Interpretation in the Holly Quran
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The present study aims at representing the importance of Quranic readings in the interpretation of the meaning of the Holly Quran in Imam Al Wahidi’s interpretation “Al Wasiet”, declaring its meaning, and eliminating of the paradox which takes place when trying to understand the intention of the Almighty Allah in His Holly book. The study aims at:

1- Defining the paradox linguistically and in terminology according to the formatives or the fundamentalists, the scientist of interpretation and of the Quranic sciences.

2-Reasoning paradox in the Quranic readings: Believing in matters that disagree with the Holly Quran and Sunnis, variety of the subjects in the verses, disagreement of the place and the place for the vers

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Publication Date
Wed Jun 29 2022
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Kinetics and Energetic Parameters Study of Phenol Removal from Aqueous Solution by Electro-Fenton Advanced Oxidation Using Modified Electrodes with PbO2 and Graphene
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The Electro-Fenton oxidation process is one of the essential advanced electrochemical oxidation processes used to treat Phenol and its derivatives in wastewater. The Electro-Fenton oxidation process was carried out at an ambient temperature at different current density (2, 4, 6, 8 mA/cm2) for up to 6 h. Sodium Sulfate at a concentration of 0.05M was used as a supporting electrolyte, and 0.4 mM of Ferrous ion concentration (Fe2+) was used as a catalyst. The electrolyte cell consists of graphite modified by an electrodepositing layer of PbO2 on its surface as anode and carbon fiber modified with Graphene as a cathode. The results indicated that Phenol concentration decreases with an increase in current dens

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Publication Date
Thu Oct 01 2020
Journal Name
Key Engineering Materials
Optimization of Electrocoagulation Process for the TSS and Turbidity Removal in Al-Qadisiyah Water Treatment Plant in Baghdad City by Response Surface Methodology
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Electrocoagulation process was employed for the treatment of river water flows in Iraq. In this study, a batch Electrocoagulation process was used to treat river water taken from Al - Qadisiyah water treatment plant. electrolysis time, voltage and inter-electrode spacing were the most important parameters to study . A statistical model was developed using the RSM model. The optimum condition after studying the parameter effect the process was 1 cm separating, 30 volts . The RSM model shows the ideal condition of removal for both the TSS and turbidity at 1 cm, 20 volts and 55 min.

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Publication Date
Sat Jan 01 2022
Journal Name
Ssrn Electronic Journal
Developing a Predictive Model and Multi-Objective Optimization of a Photovoltaic/Thermal System Based on Energy and Exergy Analysis Using Response Surface Methodology
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Publication Date
Sun Mar 03 2013
Journal Name
Baghdad Science Journal
Sedimentological and diagenetic study of the Early Middle Miocene Jeribe Limestone Formation in selected wells from Iraq northern oilfields (Ajil; Hamrin; Jadid; Khashab)
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Five subsurface sections covering the entire length of the Jeribe Limestone Formation (Early Middle Miocene) were studied from four oilfields in northern Iraq. It is hoped to unravel this formation microfacies ; depositional environment; diagenetic attributes and their parental processes; and the relationship between these processes and the observed porosity patterns. The microfacies were found to include mudstone, wackestone, packstone, and grainstone, which have been deposited respectively in open platform, restricted platform, and edge platform which represent the lagoonal environment, while the deposits of the lower parts of the Jeribe formation especially in well Hamrin- 2 reflect a deeper fore slope environment. By using the lithofac

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