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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
Wed Jan 11 2023
Journal Name
Healthcare
Short-Term (4 Day) Effects of Oral Rinsing with Miswak and Green Tea on Gingival Crevicular Fluid Flow and IL-1β Levels: A Pilot Study
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Despite the antiplaque effect of mouth-rinsing with a combination composed of miswak (Salvadora persica L.) and green tea (Camellia sinensis var. assamica) extracts, no data are available regarding its effect on gingival tissue at the molecular level. This pilot study aimed to assess the effect of oral rinsing with this combination on gingival crevicular fluid (GCF) flow and IL-1β levels. Ten subjects rinsed with either the combination, 0.12% chlorhexidine gluconate (CHX) or distilled water without toothbrushing for 4 days after receiving baseline polishing. GCF IL-1β concentration, influx, resting volume and plaque quantity were measured at baseline and after 4 days for each intervention. No significant differences in GCF flow or

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Publication Date
Fri Feb 28 2014
Journal Name
Journal Of Natural Sciences Research
Synthesis, Characterization and Antimicrobial Investigations of (Ag, Cu, Ni, Co, Mn and Hg) Complexes with Schiff Base Derived From PVA and Erythro-Ascorbic Acid Derivative
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The aim of this work is the synthesis of new Schiff base derived from PVA and Erythro-ascorbic acid derivative (pentulosono-ɣ-lactone-2,3-enedianisoate) and its metal complexes of biological significance. All synthesized compounds were characterized by Thin layer chromatography (TLC) and FTIR spectra and aldehyde was also characterized by (U.V-Vis), 1HNMR, 13CNMR and mass spectra. The synthesized Schiff base & its metal complexes were screened for their in vitro antimicrobial activity against five pathogenic bacteria (Escherichia coli, Shigella dysentery,Klebsiellapneumonae,Staphylococcusaureus, Staphylococcus Albus) and two fungal (Aspergillus Niger,Yeast).The biological activity ofall complexes is higher than free Schiff base ligand andf

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Publication Date
Tue Nov 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
Evaluation of projects during the trial operation period in accordance with the cost, quality and time - applied research in the Directorate-General for the distribution
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Research includes evaluation of projects implemented and which entered into trial operation period in accordance with the evaluation criteria and of (cost, quality and time) to determine the size deviations gap for the sample of projects during the years of assessment (2011-2012-2013-2014) of each of the three evaluation criteria, and then followed by a calculation the size of the overall gap to the problem based on the research problem to determine deviations from the specific implementation of each project by answering several questions to answer turns out the reasons for these deviations occur.

The importance of research Focus on the evaluation of received projects from contractors executing the projec

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Publication Date
Sat Jun 04 2022
Journal Name
Al–bahith Al–a'alami
Digital public relations and its role in prioritizing the masses: An analytical study of the United Nations website : (A paper extracted from a PhD dissertation)
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This paper aims to identify how the United Nations works through its website in prioritizing audiences towards international issues، by identifying the digital PR mechanisms used in digital PR contents in prioritizing audiences towards the international issues they deal with. To achieve the objectives of this paper, the researcher used the survey method and content analysis tool with a view to identifying the ranking of international issues on the website of health، peace and security، humanitarian assistance، human rights، women، migrants، refugees and displaced persons، economic development، United Nations affairs، culture and education، environment and climate، sustainable development, and law and crime prevention. One of

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Publication Date
Thu Jul 01 2021
The spontaneous emission performance of a quantum emitter coupled to a hybrid plasmonic waveguide with specified output polarization for on-chip plasmonic single-photon source
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Publication Date
Tue May 11 2021
Journal Name
Photonics And Nanostructures - Fundamentals And Applications
The spontaneous emission performance of a quantum emitter coupled to a hybrid plasmonic waveguide with specified output polarization for on-chip plasmonic single-photon source
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Nowadays, most of the on-chip plasmonic single-photon sources emit an unpolarized stream of single photons that demand a subsequent polarizer stage in a practical quantum cryptography system. In this paper, we numerically demonstrated the coupling of the light emitted from a quantum emitter (QE) at 700 nm wavelength to the propagation mode supported by an on-chip hybrid plasmonic waveguide (HPW) polarization rotator. Our results proved that the light emitted is linearly polarized at 0º, 45º/−45º, and 90º with propagation lengths of 5 μm, 3.3 μm, and 3.9 μm, respectively. Moreover, high power-conversion efficiency was obtained from an applied transverse magnetic (TM) mode (0º-polarization) to a transverse electric (TE) (90º-polari

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Publication Date
Fri Jan 20 2023
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Ibn Al-haitham Journal For Pure And Applied Sciences
Preparation, Characterization, Theoretical and Biological Study of new Complexes with mannich base , 2chloro –N-5-(Piperidin -1-ylmethylthio)-1, 3, 4- Thiadiazol-2-yl)acetamide
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A new Mannich base ligand was prepared by reacting the 2-chloro.-N-(5-mercapto-1, 3, 4-thiadazol -2-yl) acetamide and Piperidine in the presence (formaldehyde) (L) ligand. A series of ligand complexes were prepared from (L) with the metal ion Co (II), Ni (II), Cu (II), Pd (II), Pt (IV), and Au (III). Various spectroscopic techniques such as C.H.N.S, FTIR, UV-VIS, , 1HNMR, 13CNMR, Magnetic moment, and molar conductivity successfully characterize the obtained compounds. The M: L ratio was determined using the molar ratio method in solution. All prepared compounds' antibacterial and antifungal activity was studied against two types of bacteria and one type of fungi at a rate of 0.02M. The standard ΔH°

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Publication Date
Wed Apr 19 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Synthesis and Spectroanalytical Studies of a New Azodye Derived From 2-Amino-6-ethoxybenzothiazole and 4Chloro-3,5-dimethylphenol and its Complexes With Fe (III) Ion
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   This study involves the synthesis of new azodye, derived from 2-Amino-6ethoxybenzothiazole and 4-Chloro-3,5-dimethylphenol . The characterization of dye has been described by C.H.N. The TG , IR and Visible. spectroscopic techniques .The acid-base properties were studied at different pH values . The ionization and protonation constants of dye were determined. Solvents effects were also studied at different solvents polarities . The optimum conditions of this formation of complex with Fe(III) were investigated . The analytical applications of this azodye , were studied like; using it as acid-base indicator , and for the determination of nitrite ions

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Publication Date
Tue Feb 05 2019
Journal Name
Journal Of The College Of Education For Women
Social Safety Nets and its role in the protection of widows (Problems and advancement options) A field study in the Social Welfare Department for Women
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Current search problem manifested and widows who community harsh to bear hardships and pains، The goals of continuing the sustainability of life and take responsibility, and especially in light of the difficult circumstances in which Iraq is going through, and the displacement of murder and terrorism, which generated huge numbers of widows and orphans Because of the loss of a breadwinner and which became women and children are the most harm to the victim and as a result of wars and armed tendencies So this research is an important and vital topic opens our horizons important for overlapping roles of women widows and their impact on the achievement and status of Iraqi women and that as long as aptly characterized and their ability to end

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Publication Date
Tue Jun 03 2025
Journal Name
Sar Journal Of Pathology And Microbiology
The Relation between Tumor Infiltrating Lymphocyte and Classical Tumor Staging in Colorectal Carcinoma (Semi-Quantitative Study by Immun histochemistry in a Group of Iraqi Patients)
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Inflammatory response had a role in cancer progression, presence of noticeable inflammation within the tumor and its margin may play an important prognostic role in colorectal carcinoma.

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