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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
Sat Sep 28 2024
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Effect of Air–Particle Abrasion of Dentin Surface on Shear Bond Strength of Lithium Disilicate to Dentin Using Three Different Cements
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This study aims to evaluate the influence of the air abrasion of dentin on the shear bond strength of lithium disilicate using three different types of luting cements. Sixty cylindrical specimens were milled from lithium disilicate CAD/CAM blocks (IPSe.max CAD). Sixty sound human maxillary premolar teeth were decoronated to the level of peripheral dentin, then randomly divided into three groups according to the type of luting cement used for the cementation of the lithium disilicate specimens (n = 20); Group A: Glass ionomer cement (Riva Self- Cure); Group B: Adhesive resin cement (Rely X Ultimate); Group C: Self-adhesive resin cement (Rely X U200). Each group was then further subdivided into two subgroups (n=10); Subgroups AI, BI, and CI,

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Publication Date
Tue Dec 01 2020
Journal Name
2020 5th Ieee International Conference On Recent Advances And Innovations In Engineering (icraie)
The New Way of Estimating the PCB's Lifetime of Fatigue using the Principle of Linear Accumulated Damage in Various Boundary Condition
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The Role of Sox17 Gene Expression in Early Definition of Anterior Pole of the Rabbit Embryo at Early Pre-Gastrulation Stages
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Test wisdom of Postgraduate Students at the University of Samarra and its relation to the Engagement of learning and psychological tension
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The aim of the present research is to identify the test wisdom and the engagement with learning and psychological tension among postgraduate students at the University of Samarra according to the variables of the department, gender, age, and whether students are employee or non-employee. The study also attempts to identify the relationship between the test wisdom and the engagement with learning and psychological tension. The research sample consisted of (75) postgraduate students randomly selected from college of Education. The researcher applied the test–wisdom of (Mellman & Ebel) and the scale of engagement with learning preparation by (Al-zaabi 2013). In addition, the researcher used the list of the psychological stress of (Abu

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Sat Dec 30 2023
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The Role of Quality of Work Life in Reinforcing Core Competencies: A Descriptive and analytical research in the Ministry of Health
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The research aims to diagnose the shortcomings and weaknesses in applying the dimensions of the quality of work life and the extent of their impact on employees’ attitudes and behaviors, and thus their relationship to enhancing their core competencies. The scientific value of the research stems from highlighting the importance of the dimensions of the quality of professional life in improving the productive efficiency of workers in the public sector and raising the level of organizational performance. Because the quality of working life plays an important role in enhancing the core competencies of employees in the public sector, it can also be an incentive or a disincentive for any employee by adapting to the economic and social condition

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Sun Jun 04 2017
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Inflammatory role of some cytokines, immunoglobulins and complement proteins in immunopathogenesis of renal failure in a sample of Diyala province patients
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The reality of motivational administrative methods for academic decision-makers in the faculties of physical education and sports sciences of Baghdad
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Tue Jun 15 2010
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Effect of Dietary Supplementation with Sources of Omega-3 and Omega-6 Fatty Acids on Certain Blood Characteristics of Laying Quail
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The objective of this experiment was to determine the effects of dietary supplementation with different fat sources on blood parameters of Japanese quail (Coturnix coturnix japonica). Eighty four 7-week old laying quail were randomly assigned to 4 treatment groups (21 birds per group) with 3 replicates for each treatment group and fed for three months on a commercial diet supplemented with 3% of either sunflower oil (T1), flax oil (T2), corn oil (T3) or fish oil (T4). The birds received water and feed ad libitum during the experiment. During the last month of experiment blood samples were collected fortnightly from each bird. The first blood samples collection was used to determine fresh blood parameters, while the second blood samples coll

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Sun Jan 02 2011
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The necessary characteristics of the kindergarten teachers who have been recently appointed from the point of view of the kindergarten managers.
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Sun Jun 01 2014
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The economic effects of money laundering and the role of banking service in combat it: a prospective study of a sample
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Money laundering is consider a crime in legal perspective and aphenomenon of negative effects in economic and Social perspective for thevarious countries of the world by the diversity of their economies to make thebadly damaged in the banking service and its reputation in some cases may leadto bankruptcy of banks, and the fact that banks is one of the most importantcircles that revolve the illicit funds, Due to its branched the banking operations,speed and overlap and increase it's complicated with the progress of bankingoperations and the use of electronic services modern here's challenges atvarious levels between the application of the legislation to combat moneylaundering and between actual fact it must find ways and means of legislat

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