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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 Jun 05 2016
Journal Name
Baghdad Science Journal
Synthesis and characterization Studies of Metal Complexes with Schiff base derived from 4-[5-(2-hydoxy-phenyl)-[1,3,4-oxadiazol-2-ylimino methyl]-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one
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New metal complexes of the ligand 4-[5-(2-hydoxy-phenyl)-[1,3,4- oxadiazol -2-ylimino methyl]-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one (L) with the metal ions Co(II), Ni(II), Cu(II) and Zn(II) were prepared in alcoholic medium. The Schiff base was synthesized through condensate of [4-antipyrincarboxaldehyde] with[2-amino-5-(2-hydroxy-phenyl-1,3,4- oxadiazol] in alcoholic medium . Two tetradentate Schiff base ligand were used for complexation upon two metal ions of Co2+, Ni2+, Cu2+ and Zn2+ as dineucler formula M2L2.4H2O. The metal complexes were characterized by FTIR Spectroscopy, electronic Spectroscopy, elemental analysis, magnetic susceptidbility measurements, and also the ligand was characterized by 1H-NMR spectra, and m

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Publication Date
Sun Apr 30 2017
Journal Name
Journal Of Engineering
Experimental Study on Heat Transfer and Friction Factor Characteristics of Single Layer Graphene Based DI-water Nanofluid in a Circular Tube under Laminar Flow and Different Heat Fluxes as Boundary Conditions
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An experimental study was performed to estimate the forced convection heat transfer performance and the pressure drop of a single layer graphene (GNPs) based DI-water nanofluid in a circular tube under a laminar flow and a uniform heat flux boundary conditions. The viscosity and thermal conductivity of nanofluid at weight concentrations of (0.1 to 1 wt%) were measured. The effects of the velocity of flow, heat flux and nanoparticle weight concentrations on the  enhancement of the heat transfer are examined. The Nusselt number of the GNPs nanofluid was enhanced as the heat flux and the velocity of flow rate  increased, and the maximum Nusselt number  ratio (Nu nanofluid/ Nu base fluid)   and thermal performance factor

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Publication Date
Mon May 08 2017
Journal Name
Research Journal Of Pharmaceutical, Biological And Chemical Sciences
Structure, Diagnosis, and in the Vitro Antimicrobial evaluation of 2-amino pyridine-derived Ligand Schiff base and its complexes with Cu (II), Hg (II), Ni (II), Mn (II) and Co (II
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Publication Date
Mon Mar 13 2017
Journal Name
Journal Of Baghdad College Of Dentistry
A study to compare the internal fitness and marginal gap between single crowns and crowns within three-unite bridge of zirconia substructure fabricated by CAD-CAM system. (An In vitro study)
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ABSTRACT Purpose: the aim of this in vitro study was to compare the marginal gap and internal fitness between single crowns and the crowns within three-unit bridges of zirconium fabricated by CAD-CAM system. Materials and methods: A standard model from ivoclar company was used as a pattern to simulate three-units bridge (upper first molar and upper first premolar) as abutments used to fabricate stone models, eight single crowns for premolar and eight of three units bridges. Crowns and bridges fabricated by CAD-CAM system were cemented on their respective stone models then sectioned at the mid-point buccolingaully and misiodistaly and examined under stereomicroscope. Result: the marginal gap in premolar crowns and premolar within bridge we

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Publication Date
Sun Jan 01 2023
Journal Name
Results In Chemistry
Synthesis and characterization of (E)-4-(((4-(5-mercapto-1, 3, 4-oxadiazol-2-yl) phenyl) amino) methyl)-2-methoxyphenol as a novel corrosion inhibitor for mild-steel in acidic medium
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Publication Date
Thu Apr 01 2021
Journal Name
Chaos, Solitons & Fractals
Modeling and analysis of an <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si7.svg"><mml:mrow><mml:mi>S</mml:mi><mml:msub><mml:mi>I</mml:mi><mml:mn>1</mml:mn></mml:msub><mml:msub><mml:mi>I</mml:mi><mml:mn>2</mml:mn></mml:msub><mml:mi>R</mml:mi></mml:mrow></mml:math> epidemic model with nonlinear incidence and general recovery functions of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" altimg="si8.svg"><mml:msub><mml:mi>I</mml:mi><mml:mn>1</mml:mn></mml:msub></mml:math>
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Publication Date
Fri Oct 24 2014
Journal Name
Journal Of Chemical And Pharmaceutical Research
Synthesis, characterization and antimicrobial activities of [Fe(II), Co(II), Ni(II),Cu(II) and Zn(II)] mixed ligand complexes schiff base derived from amoxicillin drug and 4-(dimethylamino)benzaldehyde with nicotinamide
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New Schiff base ligand (E)-6-(2-(4-(dimethylamino)benzylideneamino)-2-(4-hydroxyphenyl)acetamido)-3,3- dimethyl-7-oxo-4-thia-1- azabicyclo[3.2.0]heptane-2-carboxylic acid = (HL) was synthesized via condensation of Amoxicillin and 4(dimethylamino)benzaldehyde in methanol. Figure -1 Polydentate mixed ligand complexes were obtained from 1:1:2 molar ratio reactions with metal ions and HL, 2NA on reaction with MCl2 .nH2O salt yields complexes corresponding to the formulas [M(L)(NA)2Cl],where M=Fe(II),Co(II),Ni(II),Cu(II),and Zn(II), A=nicotinamide .

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Publication Date
Tue Dec 30 2025
Journal Name
Journal Of Physical Education
The Effect of Special Exercises Using Handball R.T On Motor Response Development and Some Goalkeeping Skills For Handball Players from the National Center for Gifted In Handball Aged (15 – 16) Years Old
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Publication Date
Fri Oct 01 2010
Journal Name
Analytica Chimica Acta
A reversed phase high performance liquid chromatography method for the determination of fumonisins B1 and B2 in food and feed using monolithic column and positive confirmation by liquid chromatography/tandem mass spectrometry
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The development of a reversed phase high performance liquid chromatography fluorescence method for the determination of the mycotoxins fumonisin B1 and fumonisin B2 by using silica-based monolithic column is described. The samples were first extracted using acetonitrile:water (50:50, v/v) and purified by using a C18 solid phase extraction-based clean-up column. Then, pre-column derivatization for the analyte using ortho-phthaldialdehyde in the presence of 2-mercaptoethanol was carried out. The developed method involved optimization of mobile phase composition using methanol and phosphate buffer, injection volume, temperature and flow rate. The liquid chromatographic separation was performed using a reversed phase Chromolith® RP-18e column

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Publication Date
Mon Dec 25 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Extraction, Identification and Isolation of B-sitosterol from Iraqi Wild Awsaj plant (Lycium barbarum) Using UAE (Probe and Bath) and two isolation technique (HPTLC and PHPLC): B-sitosterol in Iraqi Awsaj plant
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Awsaj (Lycium barbarum) is a plant belong to family Solanaceae serves as a good source of bioactive compounds like phytosterols which have many important biological activity. Literature survey available so far revealed that there was no studies about Iraqi wild Awsaj phytosterols especially B-sitosterol, there for the objective of this study was to examine the efficiency of ultrasound assisted extraction (probe and bath) as compared to the conventional (Soxhlet) extraction method for extraction of phytosterols especially B-sitosterol from fruits, leaves, stems and roots of Iraqi wild Awsaj plant. This goal was achieved by comparing the extraction mass yield, also by a quick and easy approach for identification and quantification of bioac

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