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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
Mon Feb 04 2019
Journal Name
Journal Of The College Of Education For Women
The eloquence of the poetic image in the poetry of the Andalusian son of Labanism is a stylistic approach
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The resort to the eloquence of the poetic image as a style reveals the poet's creativity and creativity in dealing with external influences, and reflect them with emotional images express a sense of intense emotional imagination, and this imagination stems from the experience of a poetic sense of truth, tasted by the recipient before the creator of the poetic text.

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Tue Jan 01 2019
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To the Question of Internal Inflection of the Roots in Arabic and Russian (Inflected Analysis of the Root Structure)
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Tue Aug 01 2017
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Journal Of Economics And Administrative Sciences
Relationship of the key elements of Knowledge management with strategic performance / filed research sample of private banks in Baghdad
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objective  the research to diagnosis and interpretation of the nature of the correlation between the  basic elements of knowledge management (tecgnology , structure , culture , process , human resource ) and the strategic performance of the Iraqi private banks, the research community and the level dimensions, and  tested this research in the private banking sector represented by (7), especially in Baghdad city, Iraqi banks, and applied on sample consisting of 100 distributors in several administrative levels Director (Director, Director of the department, branch manager), and use questionnaire Head to collect data and information tool, and some private banks annual reports, has sought research to test a number of h

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Influence of the basic elements of knowledge management in strategic performance/filed research sample of private banks in Baghdad
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Tue Dec 01 2015
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Mon Dec 20 2021
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IMPACT OF THARTHAR ARM WATER ON COMPOSITION AND DIVERSITY OF COPEPODA IN TIGRIS RIVER, NORTH OF BAGHDAD CITY, IRAQ
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This study is considered to be the first on this sector of Tigris River after 2003, to evaluate the effect of Tharthar Arm on the composition and diversity of Copepoda in Tigris River. Six sampling sites were selected; two on the Tharthar Arm and four sites along the Tigris River, one before the confluence as a control site and the others downstream the confluence; thirty-five copepod taxa were recorded, 34 taxa in the Tigris River and 25 taxa in the Tharthar Arm.
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Study Impact of Some Factors on Daily Number of Hours Providing of Electricity in Baghdad City Using Path Analysis
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