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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 Sep 30 2002
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Effect of using Two Binders on the Agglomeration of Zeolite Type 4A
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Thu Dec 01 2011
Journal Name
Journal Of Economics And Administrative Sciences
Measurement of Impact of Banking System Development on Economic Growth in Iraq
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At the heart of every robust economy is a vital banking system. The functional banking system can effectively perform several functions such as mobilizing savings, allocating credit, monitoring managers, transforming risks, and facilitating the financial transactions. This paper aims to measure the impact of banking system development on economic growth in Iraq. Credit to private sector divided by GDP used as a proxy of banking development. Real per capita GDP used as a proxy of economic growth. By using Autoregressive Distributed Lag (ARDL) model, the paper finds that the undeveloped Iraqi banking system could not promote economic growth in the country. Therefore, a variety of policies need to be taken to spur the role of bankin

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Publication Date
Sat Aug 01 2015
Journal Name
Journal Of Engineering
Influence of Internal Sulfate Attack on Some Properties of High Strength Concrete
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One of the most important problems that faces the concrete industry in Iraq is the deterioration due to internal sulfate attack , since it  reduces the compressive strength and increases the expansion of concrete. Consequently, the concrete structure may be damage .The effects of total and total effective sulfate contents on high strength concrete (HSC) have been studied in the present study.

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Wed Jul 01 2015
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This research aims to investigate and evaluate a reactive powder concrete (RPC) cast using economical materials. Its mechanical properties were investigated and evaluated by studying the effects of using different cement and silica fume contents and locally steel fibers aspect ratios as reinforcement for this concrete. A compressive strength of about 155.2MPa, indirect tensile strength of 16.0MPa, modulus of elasticity of 48.7GPa, flexural strength of 43.5MPa, impact energy of 3294.4kN.m and abrasion loss 0.59%  have been achieved for reinforced RPC contains  910 kg/m3 cement content, silica fume content 185 kg/m3 of cement weight and fiber volume fraction 2%. The water absorption values w

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Publication Date
Sat Apr 23 2022
Journal Name
Research Journal Of Pharmacy And Technology
Synthesis, and Antimicrobial Evaluation of New hydrazone Derivatives of (2,4-dinitrophenyl) hydrazine
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In this work, novel compounds of hydrazones derived from (2,4-dinitrophenyl) hydrazine were synthesized. Benzamides derivatives and sulfonamides derivatives were prepared from p-amino benzaldehyde. Then these compounds were condensed with (2,4-dinitrophenyl) hydrazine through Imine bond formation to give hydrazones compounds. The compounds were characterized using FT-IR (IR Affinity-1) spectrometer, and 1HNMR analyses. The majority of the compounds have a moderate antimicrobial activity against “Gram-positive bacteria staphylococcus Aureus, and staphylococcus epidermidis, Gram-negative bacteria Escherichia coli, and Klebsiella pneumoniae, and fungi species Candida albicans” using concentrations of 250 µg\ml.

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Wed Jul 01 2020
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Medico-legal Update
Evaluation of quality of nursing documentationin surgical wards at baghdad teaching hospitals
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Publication Date
Sun Mar 03 2013
Journal Name
Baghdad Science Journal
Synthesis and Identification of Some New Derivative of Trimethoprim and Paracetemol Drugs
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In this research two series of the new derivatives of Trimethoprim and paracetamol drugs have been prepared which known as a high medicinal effectiveness. Series (A) is including the interaction of diazonium salt of trimethoprim and coupling with some substituted phenol compounds (2-amino phenol, 3-ethyl phenol, 1-naphthol, 2-nitro phenol, Salbutamol). Series (B) is including the interaction coupling alkali solution of paracetamol with diazonium salt of some substituted aniline compounds (Benzedine, 2, 3-di chloro aniline, Trimethoprim, Anilinium chloride, 2-nitro- 4-chloro aniline).Chemical structures of all synthesized compounds were confirmed by UV-visible and FTIR spectroscopy.

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Publication Date
Mon May 01 2023
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The Leaching Behavior of Zinc Oxide in Medical Waste of Dental Clinics
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Zinc Oxide is an indispensable substance in the field of dental treatment. It is used daily and intensively in all governmental and private dental clinics, leading to the disposal of very high concentrations of zinc with waste and eventually in landfill sites as a final destination for solid waste removal. This indicates the urgent need to investigate its behavior upon disposal due to the surrounding conditions. Approximately 4195 g of mixed dental waste samples were collected from (17) healthcare centers in Baghdad Al-Karkh. The leaching behavior of ZnO powder was investigated through batch reactors using makeup dental solid waste samples. The ZnO leaching was tested with 3 conditions; acidic, alkaline, and Ionic Streng

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Publication Date
Thu Nov 02 2023
Journal Name
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Numerical Simulation of the Thermal Performance of a Tubular Solar Air Heater
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In this work, a flat-plate solar air heater (FSAH) and a tubular solar air heater (TSAH) were designed and tested numerically. The work investigates the effect of increasing the contact area between the flowing air and the absorber surface of each heater and predicts the expected results before the fabrication of the experimental rig. Three-dimensional two models were designed and simulated by the ANSYS-FLUENT 16 Program. The solar irradiation and ambient air temperature were measured experimentally on December 1st 2022, at the weather conditions of Baghdad City- Iraq, at three air mass flow rates, 0.012 kg/s, 0.032 kg/s, and 0.052 kg/s. The numerical results showed the advantage in the thermal performance of

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Publication Date
Mon Oct 02 2023
Journal Name
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Numerical Analysis of the Stability of Bridge Foundation Pile under Earthquakes Effect
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This study was chosen because of the entry of our regions into the seismic zone recently, where Diyala governorate was hit by the Halabja earthquake in 2017 by 7.3Mw. Therefore, the impact of earthquakes will be studied on the AL-Mafraq bridge foundations piles located in Iraq- east of Baghdad in Diyala Governorate and the extent of its resistance to the Halabjah, EL-Centro, and Kobe earthquakes with acceleration 0.1g, 0.34g, and 0.58g respectively. After modeling and performing the analysis by using Midas Gts-Nx software, the settlement (mm) results at nine nodes (four nodes for the pile cap and five nodes for the piles) were obtained for each of Halabjah, EL-Centro, and Kobe earthquakes to know the resistance of the br

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