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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 Mar 30 2022
Journal Name
Iraqi Journal Of Science
Investigation of the Characteristics of CO (1-0) Line Integrated Emission Intensity in Extragalactic Spirals
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This paper aims to deal with the understanding of the properties of the molecular gas hydrogen in the extragalactic spirals sample. It is critical to make observations of CO (J = 1-0) line emission for spiral galaxies, particularly those with an energetic nucleus.  In the sample of spiral galaxies compiled, a carbon monoxide CO (1-0) emission line can be observed. This sample of galaxies' gas kinematics and star-forming should be analyzed statistically utilizing appropriate atomic gas HI, molecular gas H2, infrared (1μm-1000μm), visual (at λblue-optical=4400A0), and radio spectrum (at νradio=1.4 GHz and 5GHz) databases. STATISTICA is software that allows us to perform this statistical analysis. The presence of a high scale of s

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Publication Date
Mon Mar 23 2020
Journal Name
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Experimental Investigation of Thermal Performance of a Solar Chimney Provided with a Porous Absorber Plate
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Numerical Investigation of the Flexure Behavior of Reinforced Concrete Spandrel Beams with Distributed Tension Reinforcement
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Mon Jul 01 2019
Journal Name
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Hybrid heat transfer enhancement for latent-heat thermal energy storage systems: A review
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Thermal Enhancement from Pin Fins by Using Elliptical Perforations with Different Inclination Angles
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Mon Jan 28 2013
Journal Name
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BER performance enhancement for secure wireless communication systems based on chaotic-MIMO techniques
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The growing interest in the use of chaotic techniques for enabling secure communication in recent years has been motivated by the emergence of a number of wireless services which require the service provider to provide low bit error rates (BER) along with information security. This paper investigates the feasibility of using chaotic communications over Multiple-Input-Multiple-Output (MIMO) channels. While the use of Chaotic maps can enhance security, it is seen that the overall BER performance gets degraded when compared to conventional communication schemes. In order to overcome this limitation, we have proposed the use of a combination of Chaotic modulation and Alamouti Space Time Block Code. The performance of Chaos Shift Keying (CSK) wi

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Roller compacted concrete (RCC) is a concrete compacted by roller compaction. The concrete mixture in its unhardened state must support a roller while being compacted. The aim of this research work was to investigate the behavior and properties of roller compacted concrete when constructed in the laboratory using roller compactor manufactured in local market to simulate the field conditions. The roller compaction was conducts in three stages; each stage has different loading and number of passes of the roller. For the first stage, a load of (24) kg and (5) passes in each direction had been employed. For the second stage, a load of (104) kg and (10) passes in each direction were conducted. Finally, at the third stage, a load of (183) kg a

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Publication Date
Mon Dec 03 2018
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Error Investigation for Free Form Surfaces in Bezier Techniques
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Sat Oct 01 2011
Journal Name
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AGENT BASED MONITORING FOR INVESTIGATION PROCESS AND MAINTENANCE IMPROVEMENT
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Agent technology has a widespread usage in most of computerized systems. In this paper agent technology has been applied to monitor wear test for an aluminium silicon alloy which is used in automotive parts and gears of light loads. In addition to wear test monitoring، porosity effect on
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