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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 Jun 01 2020
Journal Name
Journal Of Engineering
Effect of Biopolymer Alginate on some properties of concrete
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Alginate from Large brown seaweeds act as natural polymer has been investigated as polymer and has been added to concrete in different percentages ( 0% , 0.5% , 1% and 1.5% ) by the cement weight and the study show the effect of using alginate biopolymer admixtures on  some of the fresh properties of the concrete (slump &  the density  fresh) also in the hardened state (  Compressive strength , Splitting tensile strength  and Flexural strength ) at 28 days. The mix proportion was (1:2.26:2.26) (cement: sand: gravel) respectively and at constant w/c equal to 0.47. The results indicate that the use of alginate as a percent of the cement weight possess a positive effect on fresh properties of co

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Publication Date
Thu May 18 2023
Journal Name
Journal Of Engineering
Simulation of Longitudinal Stability Of Helicopter In Forward Flight
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The present work describes the development of code for trim and longitudinal stability analysis of a helicopter in forward flight. In general, particular use of these codes can be made for parametric investigation of the effects of the external and internal systems integrated to UH-60 helicopters. A forward flight longitudinal dynamic stability code is also developed in the work to solve the longitudinal part of the whole coupled matrix of equations of motion of a helicopter in forward flight. The coupling is eliminated by linearization. The trim analysis results are used as inputs to the dynamic stability code. The forward flight stability code is applied to UH-60 helicopter.

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Sun Jan 01 2023
Journal Name
Rawal Medical Journal
Prevalence of bullying in primary schools of Baghdad, Iraq
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Objective: To determine the prevalence of bullying among primary schools’ children with some associated factors, and resultant effects. Methodology: This cross-sectional study with analytic elements was carried out from February through April 2022. It included a sample of 410 students from six governmental primary schools from both sides of Baghdad city. A self-constructed questionnaire was used. It comprised the following parts: Part (1): socio-demographic data, Part (2): questions that review the students’ exposure to bullying, and Part (3) entails the effects of bullying on those children. Results: The total sample was composed of 410 students; their mean age was 9.51±1.94 years. The prevalence of bullying was 56.34%. Studen

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Publication Date
Tue Dec 22 2020
Journal Name
Eurasian Journal Of Biosciences
Revision checklist of miscid flies (diptera, muscidae) of Iraq.
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Mon Sep 30 2019
Journal Name
College Of Islamic Sciences
Provisions of payment of the questioner in Islamic jurisprudence
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God has honored the man with life and decent living and warned against attacking anything that violates his sanctity without a legitimate right. Our Islamic Shari'ah has the rights to preserve the right of a Muslim in the event of any harm.

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Publication Date
Tue Dec 30 2008
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Study of the Performance of Batch Reactive Distillation Column
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Batch reactive distillation was studied in packed bed column. Esterification of methanol with acetic acid to produce methyl acetate and water with homogenous sulfuric acid as a catalyst was considered. This system was chosen because the reaction is reversible and the boiling point of reactant and products are different.
The reaction was carried out with and without distillation column and shows that the reactive distillation is more efficient from the conventional process (reactor and then separation). The conversion of acetic acid and concentration of methyl acetate increase by (30.43% and 75.14%) respectively at the best condition (reflux ratio 2, feed mole ratio 2 and batch time 90 minute).
The influence of various parameters, s

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Publication Date
Fri Feb 01 2002
Journal Name
Journal Of Engineering /college Of Eng./university Of Baghdad
Study of group action of stone columns using FEM
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Study of group action of stone columns using FEM

Publication Date
Fri Jan 01 2016
Journal Name
Chemistry And Materials Research
Synthesis of Triazolo and Pyrazolo Derivatives of Quinoline Nucleus
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New heterocyclic derivatives of quinoline are reported. Reaction of quinoline-2-thiol 4 with hydrazine hydrate gave 2-hydrazionoquinoline 5. Treatment of 5 with CS2 in pyridine afforded 1,2,4-triazolo-[4,3-a]- quinolin-1-2H-thione 6, whereas the reaction of 5 with carboxylic acids namely formic acid or acetic acid, yielded the 1,2,4-triazol-[4,3-a]-quinolin 7 or 5-methyl-1,2,4-triazolo [4,3-a]-quinoline 8 through ring closure. Diazotization of 5 under acidic conditions produced the fused tetrazole compound 9, tetrzolo-[1,5-a]- quinoline. Moreover, treatment of 5 with active methlyene compounds gave two pyrazole derivatives 10 and 11. Azomethines 12a-e were prepared through condensation of 5 with aromatic aldehydes or ketones.

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Publication Date
Sun Jan 26 2020
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Evaluation of Financial Performance of the Iraqi Insurance Company
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Insurance Companies perform a prominent role in providing services and bolstering national economy, and they contribute in achieving the aims of the economic development plans in addition to many other social and economic benefits. So it is necessary to evaluate the activity of these companies continuously to define performance level and its nature. Financial analysis is one of the important instruments that helps in analyzing and explanation of data in such a way that enable administration to define performance level and diagnosing strength and weakness points. This study tackles the state of affairs of the Iraqi Insurance Company which is considered as one of the active national institutions, due to its distinguished role in collecting

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Publication Date
Fri Mar 30 2001
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Study of Performance of Air Filters in Public Shelters
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