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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 Dec 31 2018
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
ESTIMATION OF LEAD ELEMENT IN THE BLOOD OF TRAFFIC POLICE IN THE CITY OF BAGHDAD.: ESTIMATION OF LEAD ELEMENT IN THE BLOOD OF TRAFFIC POLICE IN THE CITY OF BAGHDAD.
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The current study aimed to determine the relation between the lead levels in the blood traffic men and the nature of their traffic work in Baghdad governorate. Blood samples were collected from 10 traffic men and the age about from 20-39 year from Directorate of Traffic Al Rusafa/ Baghdad and 10 samples another control from traffic men too with age 30-49 year and they livedrelatively in the clear cities or contained of Very few traffic areas. The levels of lead in blood estimated by used Atomic Absorption Spectrometry.
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Sat Aug 23 2025
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The Role of Media Coverage of the Iraqi Satellite Channels in Shaping Public Attitudes towards Terrorism (a Field Study of a Sample of an Audience of the City of Baghdad)
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Journal Name
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Reflection of knowledge workers characteristics on knowledge acquision “Survey Study of the views of a sample of engineers and technicians in the Directorate of Electricity In the city of Sulaymaniyah
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Purpose: The research aims to diagnose the current availability of knowledge workers characteristics and the role of these characteristics in knowledge acquision in the city of Sulaimaniya Directorate of Electricity, and to identify the differences between personal and occupational characteristics of a sample of research and its impact on the availability of such properties.

Design/methodology/approach :to achieve the objectives of the research questionnaire was developed especially for it and then distributed to a sample of engineers and technicians working in the Directorate of Electricity city of Sulaimaniya, where the sample of the research (52) respondents.

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Employ of Public Relations in Building Awareness of Security against Terrorism A Survey of the Employees of the Directorate General of Public Relations and Media at the Ministry of Interior
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STUDY OF YIELD AND ITS COMPONENTS OF INTRODUCED VARIETIES OF MAIZE UNDER DIFFERENT PLANTING DENSITIES: STUDY OF YIELD AND ITS COMPONENTS OF INTRODUCED VARIETIES OF MAIZE UNDER DIFFERENT PLANTING DENSITIES
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In order to evaluate the performance of introduced varieties of maize and test them under different levels of plant density, and to determine which of the introduced varieties give a high yield and at what plant density, a field experiment was carried out at Station A in the Department of Field Crops- College of Agricultural Engineering Sciences - University of Baghdad- Jadiriyah, for the fall season 2021, the RCBD design was used with four replications, in a split plot arrangement, the three plant densities (50.000, 70.000, and 90.000 Plant s ha-1) were the main plates, while the varieties represented the secondary factor, which is six varieties of maize, class 2 = 5783 DKC, Class 3 = 6315 DKC, Class 4= 6590 DKC, whic

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Publication Date
Sun May 07 2017
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Effect of stretching exercises on the muscles of the body in the development of the length and frequency of the strike of the arms free swimming for students of faculties of physical education and sports sciences
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Mon Feb 04 2019
Journal Name
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Abstract
This study aims to evaluated the user satisfaction of retrieval services
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2- Recognizing the reasons in this unit behind the case of non satisfaction of
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Publication Date
Sun Jan 20 2019
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A chemical study was carried out to evaluate the efficiency of the liver enzyme concertation and uric acid level and its antagonists in the serum of the professors exposed to chemicals in the laboratories of the University of Samarra and their comparison with the healthy people. The research included 25 samples of the exposed professors and 20 samples as a group of officers.

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