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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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Tue Feb 14 2023
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The Evaluation of Educational Quality Management and the Way to Improve It in the College of Education for Women at the University of Baghdad from the Teachers’ Point of View
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Fri Dec 31 2021
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Sun Oct 01 2017
Journal Name
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Wed Jun 07 2023
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The Contribution of Behavioral Disorders to Predicting Bullying Patterns in a Sample of Adolescents with Autism Spectrum Disorder: College of Education and Arts - Northern Border University - Kingdom of Saudi Arabia.
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The present study aims to identify the role of behavioral disorders (anxiety disorder, behavior disorder "behavior", confrontation and challenge disorder, aggressive behavior) in predicting bullying patterns (verbal, physical, electronic, school) in a sample of adolescents with autism spectrum disorder. For this purpose, the researcher developed scales to measure the behavioral disorders and the bullying patterns among adolescents with autism spectrum disorder. The researcher adopted the descriptive survey approach. The study sample consists of (80) adolescents with autism spectrum disorder with ages range from (15-19 years) and (45-53 years old) in association with israr association for people with special needs in the northern borders

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Wed Oct 01 2014
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Mon Dec 31 2018
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EXPOSURE TO TELEVISION PROMOTION OF PHARMACEUTICAL PRODUCTS AND TRENDS TOWARDS THEM / FIELD RESEARCH FOR A SAMPLE OF THE AUDIENCE IN THE CITY OF BAGHDAD: EXPOSURE TO TELEVISION PROMOTION OF PHARMACEUTICAL PRODUCTS AND TRENDS TOWARDS THEM / FIELD RESEARCH FOR A SAMPLE OF THE AUDIENCE IN THE CITY OF BAGHDAD
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A field study was conducted on a sample of the public in Baghdad to study the audience's exposure to the television promotion of pharmaceutical products and their trends in order to determine the rate of exposure of the public to the television promotion of pharmaceutical products according to the theory of uses and rumors and to determine the public's attitudes towards television promotion of pharmaceutical products. A survey of (25) a questions was distributed to a sample of the audience of 150 people. The statistical program SPSS was used to unload the data and for the calculation of frequencies and percentages and correlation coefficients. The research reached several results, Most importantly, the television promotion is well receiv

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Sun Sep 01 2013
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synthesis of poly condensation
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