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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
Fri Jun 16 2023
Journal Name
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The Role and Importance of Electronic Automation in Banking Service Development: A Case Study of the Commercial Bank of Iraq
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Effect of Teaching Competencies in Enhancing Self-Confidence among Students of Department of Art Education during Application: كنعان غضبان حبيب
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The results of previous scientific studies showed that knowledge is something and application is something else, that's why teachers' preparation programs focused, in the present time, on special standards for knowledge and performance, i.e., who has knowledge is not necessary able to apply it in his life or in his field of work, which led to the existence of a gap between knowledge and application. Based on that, those interested in (teachers' preparation) reconsidered their work evaluation, thus the concept of competency appeared at the end of the sixties of the past century to address the negative in teachers' preparation.
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Tue Mar 27 2018
Journal Name
Mustansiria Dental Journal
The Effect of Modified Carisolv Gel on Surface Roughness of two Different Types of Ceramic Materials Using Light Polarizing Microscope
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This in vitro study evaluated the influence of chemomechanical caries removal solution on the surface topography of metal-ceramic feldspar porcelain (MAJOR ceramic) and All-ceramic feldspar porcelain (Vita Alpha) using light polarizing microscope. Forty specimens of MAJOR ceramic and forty specimens of Vita Alpha ceramic of (12mm diameter & 3mm height) were prepared .All specimens were polished with silicon polishing burs, cleaned, autoglazed and stored in 37°C before exposure to Carisolv. Thirty specimens of each material randomly exposed to Carisolv gel for 5, 10 and 20 minutes respectively, other ten specimens were not, to act as control group. All specimens were subjected to surface roughness test by profilometer and evalua

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Journal Name
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The Spectrum and the Numerical Range of the Product of Finite Numbers of Automorphic Composition Operators on Hardy Space 2
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Throughout this paper we study the properties of the composition operator
C
p1  o
p2  o…o
pn  induced by the composition of finite numbers of special
automorphisms of U,
pi  (z)  i
i
p z
1 p z


Such that pi  U, i  1, 2, …, n, and discuss the relation between the product of
finite numbers of automorphic composition operators on Hardy space H2 and some
classes of operators.

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Publication Date
Tue Aug 01 2017
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Thermal Analysis of Double-Pass Solar Air Collector with Different Materials of Absorber Plate and Different Dimensions of Air Channels
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Tue Feb 03 2026
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The influence of adding of modified ZrO2-TiO2 nanoparticles on certain physical and mechanical properties of heat polymerized acrylic resin
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The effect of addition of hydroxyapatite microscopic fillers on surface roughness and some mechanical properties of heat cured acrylic resin
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Measuring the quality of office services using (LibQUAL + ®): the central library of the University of Baghdad as a model
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Wed Dec 01 2010
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