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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 Feb 10 2019
Journal Name
Journal Of The College Of Education For Women
The Sources of the Narrative of Siffin Agreement
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We can conclude that version A is substantially genuine while version B is spurious. an Attempt has been made above to show relevance of this to our understanding of the agreement itself .
The central issue of sunna to which recourse was to be had must of course be connected with development of the meaning of the word sunna from the broader (way of Proceeding ) and (generally agreed practice).
Any sweeping judgements about the invalidity of reports transmitted by shiis or supposed shii are out of place. theestablishment of realistic criteria for the appreciation of early sources for Islamic history is subject which is still in Its infancy

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Publication Date
Thu Jun 30 2016
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Experimental Study of Thermophysical Properties of TiO2 Nanofluid
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Titanium-dioxide (TiO2) nanoparticles suspended in water, and ethanol based fluids have been prepared using one step method and characterized by scanning electron microscopy (SEM), and UV–visible spectrophotometer. The TiO2 nanoparticles were added to base fluids with different volume concentrations from 0.1% to1.5% by dispersing the synthesized nanoparticles in deionized water and ethanol solutions. The effective thermal conductivity, viscosity and pH of prepared nanofluids at different temperatures from 15 to 30 oC were carried out and investigated. It was observed that the thermal conductivity, pH, and viscosity of nanofluids increases with the increase in TiO2 nanoparticle volume fraction

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Publication Date
Sun Sep 04 2011
Journal Name
Baghdad Science Journal
Determination of bacterial contamination of milk using fluorometry
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The aim of this paper is to determine the feasibility of using fluorometric methods as an indicator for quality and contamination of milk with E.coli bacteria, and selection the suitable wavelength to be used with laser induced auto fluorescence. Three groups of milk samples were used in this study: Fresh pasteurized milk samples, milk samples containing different concentration of E.coli bacteria which were added artificially, and milk samples that were kept in refrigerator for 3-5 days. Thirteen excitation wavelengths were used to get the emission spectra for all milk samples using spectroflourometer .The results showed that the emission spectra at 275nm excitation wavelength gave a good differentiation between these three groups.

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Publication Date
Sun Jan 16 2011
Journal Name
Bayt Alhekma
formations of abstract nouns from groups of goagols
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Abstract The study aimed at reviewing translation theories proposed to address problems in translation studies. To the end, translation theories and their applications were reviewed in different studies with a focus on issues such as critical discourse analysis, cultural specific items and collocation translation.

Publication Date
Sun Dec 30 2012
Journal Name
College Of Islamic Sciences
A study of the hadiths of supplication orchestration
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A study of the hadiths of supplication orchestration

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Publication Date
Sat Apr 01 2023
Journal Name
Baghdad Science Journal
Detour Polynomials of Generalized Vertex Identified of Graphs
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The Detour distance is one of the most common distance types used in chemistry and computer networks today. Therefore, in this paper, the detour polynomials and detour indices of vertices identified of n-graphs which are connected to themselves and separated from each other with respect to the vertices for n≥3 will be obtained. Also, polynomials detour and detour indices will be found for another graphs which have important applications in Chemistry.

 

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Publication Date
Thu Sep 30 2004
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Production of Formaldehyde by Catalytic Conversion of Methanol
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Publication Date
Wed Mar 01 2023
Journal Name
Baghdad Science Journal
Sum of Squares of ‘n’ Consecutive Carol Numbers
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The discussion in this paper gives several theorems and lemmas on the Sums of Squares of  consecutive Carol Numbers. These theorems are proved by using the definition of carol numbers and mathematical induction method. Here the matrix form and the recursive form of sum of squares of  consecutive Carol numbers is also given. The properties of the Carol numbers are also derived.

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Publication Date
Fri Dec 30 2011
Journal Name
Al-kindy College Medical Journal
Outcome of surgical treatment of highgrade intramedullary astrocytomas
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Background: Intramedullary astrocytomas
account for about 1% of all CNS tumors and
6–8% of spinal cord tumors. The vast majority
of intramedullary astrocytomas are slowgrowing
lesions.
Objectives: The goal in this study was to
review a series of patients who underwent
surgical removal of intramedullary high-grade
astrocytomas, focusing on the functional
outcome and the effect of multimodality
treatment on the survival of patients with high
grade intramedullary astrocytoma.
Methods: Between June 1999 and June 2004,
22 patients underwent removal of
intramedullary high-grade astrocytomas in four
neurosurgical hospital in Baghdad/ Iraq
(Neurosurgical hospital, Al Shaheed Adnan
Hospital for

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Publication Date
Sat Mar 31 2018
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Kinetics of Thermal Pyrolysis of High-Density Polyethylene
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Thermal pyrolysis kinetics of virgin high-density polyethylene (HDPE) was investigated. Thermal pyrolysis of HDPE was performed using a thermogravimetric analyzer in nitrogen atmosphere under non-isothermal conditions at different heating rates 4, 7, 10 °C/min. First-order decomposition reaction was assumed, and for the kinetic analysis Kissinger-Akahira-Sunose(KAS), Flynn-Wall-Ozawa(FWO) and Coats and Redfern(CR) method were used. The obtained values of  average activation energy by the KAS and FWO methods were equal to137.43 and 141.52 kJ/mol respectively, these values were considered in good agreement, where the  average activation energy value obtained by CR equation methods was slightly different which equal to 153.16 kJ/

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