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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
Iraqi Journal Of Physics
A study of the effect of acid immersion on some physical properties of ( Epoxy – MgO) composites
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In this study a polymeric composite material was prepared by hand
lay-up technique from epoxy resin as a matrix and magnesium oxide
(MgO) as a reinforcement with different weight fraction (5,10,15,
and 20)% to resin. Then the prepared samples were immersed under
normal condition in H2So4(1 M) solution, for periods ranging up to
10 weeks. The result revealed that the diffusion coefficient
decreasing as the concentration of MgO increase. Also we studied
Hardness for the prepared samples before and after immersion. The
result revealed that the hardness values increase as the concentration
of MgO increase, while the hardness for the samples after immersion
in H2SO4 dec

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Publication Date
Fri May 01 2009
Journal Name
Diyala Journal For Pure Science
Synthesis of Schiff bases of 2-thio-5-aryl-1,3,4- oxadiazole derivatives of possible biological activity
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In this study, new derivatives of Schiff bases of 2-thio-5-aryl1,3,4-oxadiazole have been synthesized. The structures of these derivatives were characterized from their melting points, infrared spectroscopy and elemental analysis. The Schiff bases derivatives were tested for inhibition of E-coli and were all found to be active.

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Publication Date
Tue Jul 12 2022
Journal Name
Proceedings Of Seventh International Congress On Information And Communication Technology
Identification of Key Criteria of Selecting the Delivery System and Type of Contract in Construction Projects
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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Effect of crude extracts of the plant local wolf riding in the growth of some fungi
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Make a search on the vegetative parts of the plant local horse guilt of some elements in the Haj Omran area in northern Iraq has included recognition of certain nutrients

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Publication Date
Wed Jun 29 2022
Journal Name
College Of Islamic Sciences
The question of demand: definition, divisions, and examples from the controversy of the scholars of jurisprudence.
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research summary

Praise be to Allah، and prayers and peace be upon His Messenger and His chosen one، his family، companions and his family and his family.

After that، this is a study on the question of the claim، as one of the controversial questions that are the mainstay of debates، and I looked at it: the limit of the question of the claim، its importance، its impact، its aspects of corruption، its sections، and the representation of its sections of the fundamentalist controversy;

The research was according to the following plan:

Introduction، in which she mentioned: the importance of the research topic and the reason for its selection، its questions، its l

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Publication Date
Sat Jan 02 2021
Journal Name
Journal Of The College Of Languages (jcl)
A Study of Feminist Stylistic Analysis of Language Issues of Gender Representation in Selected Literary text
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Stylistics is the analysis of the language of literary texts integrated within  various approaches to create a framework of different devices that describe and distinct a particular work. Therefore, feminist stylistics relied on theories of feminist criticism tries to present a counter- image of a woman both in language use and society, to draw attention , raise awareness and change ways that gender represents. Feminist stylistic analysis is related not only to describe sexism in a text, but also to analyze the way that point of view, agency, metaphor, and transitivity choices are  unanticipatedly and carefully connected to issues of gender(Mills,1995:1)            &nb

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Publication Date
Wed Jan 23 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The impact of external borrowing to bridge the federal budget deficit of the Republic of Iraq
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 The deficit budget, one of the results of increased public spending for their revenues due to the economic pressures imposed by the interest of the economies of those countries from the need to increase government spending in order to revitalize the national economy and accelerate economic growth rates and provide employment to the growing levels of unemployment in those countries opportunities and what is required to address the current debt crisis (borrowing), which has become a big burden on the governments and the need to move towards the application of austerity spending and tax increases, which inevitably forced those countries will be reflected reduced spending on basic aspects of life and their peoples, particularly earners

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Publication Date
Tue Nov 18 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Comparison of regional bond strength among different types of posts luted with different types of cement
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Background: This in vitro study was carried out to investigate the effect of post space regions (coronal, middle and apical), the effect of post types ( Manually Milled Zirconia post, Prefabricated Fiber post, prefabricated Zirconia post) and the type of cement used (GIC, self-adhesive resin cement) on the bond strength between the posts and root dentin by using push-out test. Material and methods: Forty eight mandibular premolars extracted for orthodontic reasons (single rooted) were instrumented with ProTaper system (hand use) and obturated with gutta percha for ProTaper using AH26® root canal sealer following the manufacturer instructions. After 24 hours, post space was prepared using Zirix and Glassix drills no.3 creating 8 mm dept

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Publication Date
Sun Mar 07 2010
Journal Name
Baghdad Science Journal
The role of some types of erythrocytes on the growth of Entamoeba histolytica trophozoite in vitro
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The parasite E.histolytica was first isolated from a stool sample, and then cultivated and maintained in vitro using Locke-egg medium (LEM) and Liver infusion agar medium (LIAM) . Then, the effect of some types of erythrocytes (human and sheep), on the growth and activity of the parasite in the two culture media was investigated. The parasite was able to ingest and lysis erythrocytes of human and sheep that were supplemented to the culture media and such manipulation was able to augment the reproduction rate of the cultivated E. histolytica, however, such consequence was media- and concentration-dependent. The reproduction rate was significantly increased (66.0, 57.5 and 58.6%, respectively) in LEM medium containing human erythrocytes ty

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Publication Date
Wed Dec 31 2014
Journal Name
Complex Metals
Formation of polymeric assemblies of six-coordinate metal complexes with mixed bridges of dicarboxylato-azido moieties
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New biscarboxylato zwitterionic ligands, namely bis(N-carboxylatoethyl)-4,4 -dipyridinum) L1 and bis(Ncarboxylatopropyl)-)-4,4 -dipyridinum) L2, were synthesized from the reaction of 4,4 -dipyridine with 3-bromopropanoic acid and 4-bromobutanoic acid, respectively. The reaction of these ligands and the azido coligand with some metal ions resulted in the formation of polymeric complexes of general formulae [Cr2(Ln)(N3)4]Cl2·H2O and [M2(Ln)(N3)4] xH2O, where (M = Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II); n = 1, 2; x = 1, 1, 1, 1, 0, 1, and 1, respectively.) The oxygens of the carboxylato group are coordinated to the metal ion in a bidentate fashion. The mode of bonding and overall geometry of the complexes were determin

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