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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 Jan 01 2015
Journal Name
International Journal Of Astronomy And Astrophysics
Determination of Velocity and Radius of Supernova Remnant after 1000 yrs of Explosion
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Supernova explosions are described as very violent events which transfer a significant amount of energy to interstellar media and are responsible for a large variety of physical processes. This study does not discuss the actual explosion mechanisms but follows the behavior of the dynamical evolution of some selected type I and type II supernova remnant and particularly after a thousand years from their explosion and shows how the density of the medium affects the evolution and the lifetime of each remnant. By studying such behaviors, a simplified model has been proposed here for the velocity and radius of the remnant after thousand years of explosion that depends only on the density of the medium and age of the remnant. It has been found th

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Publication Date
Mon Jun 22 2020
Journal Name
Systematic Reviews In Pharmacy
Effect of Application of BMP2/TGF β1 in Traumatic Pulp of Osteoporotic Rat
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Introduction: Dental pulp tissue contains many undifferentiated mesenchymal cells, which have the ability to differentiate into different specialized cells. Induced pluripotent stem cells have been developed by various growth factors. The present study was designed to evaluate the effect of application of a combination BMP2/TGF β1 as capped material for traumatic pulp in osteoporotic rat. Materials and Methods: Twelfth female rats (6 normal rat and other 6 osteoporotic rat)., their maxillary anterior teeth subjected to mechanical traumatized pulptomy, the left tooth has speared without treatment, while the right tooth capped with application of 0.5 μl of BMP2 and 0.5μl of TGF β1 .Evaluation of histological changes includes scoring of pu

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Publication Date
Mon Mar 01 2010
Journal Name
Al-khwarizmi Engineering Journal
The Study of Ability of Local Ninivite Rocks in Purification of Drinking Water
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This study is conducted to verify the efficienecy of local Ninivite rock when used in the treatment of drinking water in plants operating currently in the country in order to develop the situation of these stations to cope with the increase in population. Also, this will limit the pollutian which are increasing in the country's rivers.

(Euphrates and Tigris). These rivers are the sources to feed all water treatment plants in the country. The idea is the develop or the modify these stations by replacing part of top layer of sand filters used in these stations with Ninivite rock to operate as filters composed of two medium. The efficiency of this rock is compared with other materials used successfully worldwide in this area, such a

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Publication Date
Fri Dec 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
Effect of the Quality of Accounting Information on the Efficiency of Investment Decisions
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Abstract

The entities responsible for regulating the financial market are seeking to provide high quality accounting information, to provide appropriate protection to investors, and thus encourage them and attract them to increase their investments. the research reached several conclusion, the most prominent of which comes  :-

1-The production of high quality accounting information reduces investment costs and costs of processing accounting information.

2- The production of high quality accounting information helps investors identify the best investment opportunities.

3- The results of the statistical analysis showed that there is significant

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Publication Date
Sun Jun 30 2002
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
A study of the Rate of Sedimentation of Magnesium Hydroxide Obtained from Bittern
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Publication Date
Thu Oct 18 2018
Journal Name
Journal Of Economics And Administrative Sciences
Effect of Attitudes in the ethics of the public job of the individual
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Attitude is an important subject that has attracted researchers and thinkers in organizational theory and organizational behavior because of its great importance in various field studies. Field evidence suggests that individuals in their daily lives or careers respond to specific events through a set of internal tendencies Internal tendencies are negative or positive and systematic. These trends tend to be invisible, not limited to certain boundaries, and involve a significant number of individuals within organizations or society.

 The research aims to identify the impact of trends in the ethics of public service workers for individuals, through a sample of (72) doctors and (60) administrative staff

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Publication Date
Mon Jan 28 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Economic analysis of the investment of human capital and the policy of privatization
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The research problem is dedicated to investigate reservoirs irrational economic behavior adopted by the ruling elites in developing countries about the investment methodology of human capital and operating policies is based on the terms of reference of economic theory and standards governing the market, which led to a chronic structural imbalance in the workforce structure and lack of consistency with different production structure, in turn, which had a reported effects in the emergence of the phenomenon of unemployment and that they involved a certain privacy, as has become the issues of unemployment and employment in the various countries of the world are issues more important due to the presence of large numbers of the workforce in th

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Publication Date
Sun Jun 30 2019
Journal Name
Journal Of The College Of Education For Women
Qualities of Life Partner from the Perspective of a Sample of University Students
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The study aims at identifying the morphological and psycho-socio-economic qualities wished to be in a life partner among a sample of Palestinian youth. The total sample was (231) and consisted of  (83) male and (148) female students. Each student presented a detailed report on the qualities he/she wished to be in life partner. The study used the descriptive approach and content analysis method. The validity and stability of the analysis were calculated. The results showed eight qualities in both groups: physical, psychological, emotional, social, intellectual, familial, economic and academic. Female students were found to have more variations than male students in terms of the qualities preferable in the life partner. Male students

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Publication Date
Fri Jan 06 2012
Journal Name
Journal Of Engineering
Effect of change in the coefficient of permeability on consolidation chacractertistics of clay
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Publication Date
Sun Jan 27 2019
Journal Name
Journal Of The College Of Education For Women
Effect of the activity of Boswellia Carterii extracts on preservation of ground meat
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The study aimed to know the effect of the use alcoholic ethanol extraction of Boswellia Carterii In prolonging the period of preservation cooled ground meat in 4C for 6 days, it has been mixing ground meat with 150,300,450 mg/ml of alcoholic extract Consecutive, Where (0 was the control sample), All samples were stored separately for 0 , 3 , 6 days in Refrigerator temperature 4 C, Conducted by some microbial tests, Results have shown that mixing the ground meat with Boswellia Carterii extraction Led to prolong the storage of meat for 6 days at 4 C .and the Best result came when adding alcoholic ethanol extract of Boswellia Carterii by 450mg/ml Which Equal 0.9 g ,that reducing microbial load more higher than 150&300 mg/ml. All of thes

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