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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
Thu Oct 01 2015
Journal Name
Journal Of Engineering
Strength Enhancement of Prestressed Concrete Dapped-End Girders
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This paper presents the application of nonlinear finite element models in the analysis of dapped-ends pre-stressed reinforced concrete girders under static loading by using ANSYS software. The girder dimensions are (4.90 m span, 0.40 m depth, 0.20 m width, 0.20 m nib depth, and 0.10 m nib length) and the parameters considered in this research are the pre-stress effect, and strand profile (straight and draped).

    The numerical results are compared with the experimental results of the same girders. The comparisons are carried out in terms of initial prestress effect, load- deflection curve, and failure load. Good agreement was obtained between the analytical and experimental results. Even that, the

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Publication Date
Thu Oct 21 2021
Journal Name
International Journal Of Research In Social Sciences And Humanities
The Role of Green Kaizen in Productivity Enhancement
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The world is moving towards greening business in general and production systems in particular. At the same time, economic units seek to enhance their productivity and find any variables that can contribute to improving their elements. Economic units should not ignore the green dimension of cost management techniques because of its role in containing the green dimension of the production system and the product. However the few researches dealt with the subject of the green kaizen showed its role in reducing costs and improving the environment. Those researches did not address its contribution to raising the level of productivity. Productivity is an important indicator of economic units that expresses their level of success and progre

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Publication Date
Thu Oct 01 2015
Journal Name
Journal Of Engineering
Strength Enhancement of Prestressed Concrete Dapped-End Girders
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This paper presents the application of nonlinear finite element models in the analysis of dappedends pre-stressed reinforced concrete girders under static loading by using ANSYS software. The girder dimensions are (4.90 m span, 0.40 m depth, 0.20 m width, 0.20 m nib depth, and 0.10 m nib length) and the parameters considered in this research are the pre-stress effect, and strand profile (straight and draped). The numerical results are compared with the experimental results of the same girders. The comparisons are carried out in terms of initial prestress effect, load- deflection curve, and failure load. Good agreement was obtained between the analytical and experimental results. Even that, the numerical model was stiffer than the experiment

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Enhancement of Atorvastatin Tablet Dissolution Using Acid Medium
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         In this study some generic commercial products of Atorvastatin tablets were evaluated by dissolution test in acid medium by comparing with that of parent drug Lipitor of Pfizer Company. Some of solubilizing agents were studied in formulation  of Atorvastatin tablet including;  surface active agent  and PEG 6000 .The most effective factor was the  use of PEG6000 in formulation of Atorvastatin tablet which improved the dissolution and the results of dissolution profile of formulated tablet in this work  was bioequivalent to that of Lipitor .The quantitative analysis of this work was performed by using reversed phase liquid chromatography and a proper mixture of &nbsp

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Wed Dec 13 2017
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Performance Enhancement of the South Baghdad Thermal Station
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Aim of the research is the study of improving the performance of the thermal station south Baghdad and the main reasons for reduced its efficiency. South Baghdad power planet comprises (6) steam turbine units and (18) gas turbine units .The gas turbine units are composed of two groups: the first group is made up of gas units (1,2), each of capacity (123) MW. The design efficiency of gas turbine units is 32%. The actual efficiency data of steam units is 18.3% instead of 45% which is the design efficiency. The main reason for efficiency reduction of gas units is the rejected thermal energy with the exhaust gases to atmosphere, that are (450-510) ℃.The bad type of fuel used (heavy) fuel. Another reason for the low efficiency and has a neg

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Publication Date
Wed Jan 21 2015
Journal Name
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Theoretical analysis of nuclear radius measurement using nuclear structure models and Figuretechnology-enhanced computational approaches
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Bi-objective Machine Scheduling Using Enhanced Simulated Annealing and Bee Algorithm Approaches
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Many industrial systems involve multiple criteria and objectives, and they are very complex problems in computational science, such as task scheduling. We propose bi-criteria and bi-objective scheduling problems, which are solved by two nature-inspired evolutionary algorithms, such as Simulated Annealing (SA) and Bee Algorithm (BA). This problem is characterized by scheduling a batch of tasks on multiple machines, and it is fundamental because the solution should focus on the simultaneous optimization of two conflicting objectives: the makespan minimization and the total tardiness minimization. This problem is NP-Hard, and therefore, two evolutionary methods were used to search for solutions intelligently in this huge, very complex

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Wed Dec 09 2015
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Effect of Sodium sulfite treatment on the trypsin inhibitors activity, protein isolate and protein solubility of complete and dehulling white bean seeds Phaseolus vulgaris.: Effect of Sodium sulfite treatment on the trypsin inhibitors activity, protein isolate and protein solubility of complete and dehulling white bean seeds Phaseolus vulgaris.
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The study aimed to increase the biological value of white bean. The effect of different concentrations 0.01 ,0.02,0.03,and 0.04 M of sodium sulfite solutions for 1hr at 70 ºC on the trypsin inhibitors activity, protein isolate and protein solubility of complete and dehulling white bean flour were studied.Trypsin inhibitors activity were reduced by 42.97, 58.69, 68.59 and 69.58% in complete white bean flour at 0.01 ,0.02, 0.03, 0.04 M respectively, while the corresponding values were 50.43, 61.00, 75.61 and 85.66% respectively in dehulling white bean flour .Protein isolate value was 13.41% and protein solubility was 2.2% in control sample, Furthermore, the using of chemical treatment showed that protein isolate was reduced gradually and

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