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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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Determination of classes of armature when reinforcement is mixed
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Mon Dec 01 2014
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Cytotoxicity of myriocin against axenic culture of Leishmania mexicana
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Serine Palmitoyltransferase SPT is the key enzyme in the de novo sphingolipids biosynthesis pathway in eukaryotes, including the intracellular parasite Leishmania. Previous studies showed that this enzyme SPT is expressed only in divided promastigote forms and it is non-essential in the amastigotes form of Leishmania major, which is known as the old world leishmaniasis. In this study we have studied the viability of new world lesihamniasis, Leishmania mexicana. Cytotoxicity test used to determine the effect of the SPT inhibitor myriocin which did not significantly affect the viability of the two forms of the in vitro cultures of the parasite p<0.05, procyclic promastigotes and amastigotes, in which cell viability for miltefosine trea

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Wed Sep 30 2015
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The provisions of luxury in the performance of worship
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The luxury of the grace and the extension of the vioa of the subjects that attract two teams of opinion,
Addame
QF Faba believes that
Meet
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And poverty is the best in human life, and others see it
And Joe titling
Grace, and not for man to suffer as long as stigmatized and

Try not to have money.
And in recent years
G
F
S

A lot of people bypassing
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I see who says austerity in
Thou shalt not see grace
Color of and
Luxury has been promoted to the religious life of
M

A lounge
And others, and a team of worshipers to distance themselves from the mantle of turquoise,
Faleh me
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Effect of Additives on Rheological Properties of Invert Emulsions
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This research deals with study of the effect of additives on rheological properties (yield point, plastic viscosity ,and apparent viscosity) of emulsions. Twenty seven emulsion samples were prepared; all emulsions in this investigation are invert emulsions when water droplets are dispersed in diesel oil. The resulting emulsions are called water-in-oil (W/O) emulsions. The rheological properties of these emulsions were investigated using a couett coaxial cylinder rotational viscometer (Fann-VG model 35 A), by measuring shear stress versus shear rate. It was found that the effect of additives on rheological properties of emulsions as follow: the increase in the concentration of asphaltic material tends to increase the rheological propertie

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Fractographic Analysis of Tensile Failures of Zirconia Epoxy Nanocomposites
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This work characterizes the fractographic features of the neat epoxy and ZrO2 epoxy nanocomposites. All samples were subjected to a tensile test to determine the tensile strength and tensile modulus. SEM images were used to study the morphology of the fractured surface. The fractographic of the fracture surfaces were studied by microstructure analysis program (j-images) to specify the effect of ZrO2 nanoparticles on tensile performance and failure mechanism for ZrO2 epoxy nanocomposites. The tensile test results show that the addition of ZrO2 nanoparticles (2, 4, 6, 8, and 10 vol.%) to the epoxy matrix leads to increase the tensile strength about 40% for optimal content of ZrO2 nanop

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April 1993 to May 1999. The diagnosis of TOF established
by echocrdiographic, catheterization and angiographic
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Mon Dec 01 2008
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