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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 Dec 01 2011
Journal Name
Journal Of Economics And Administrative Sciences
Organizational Transparency influence in reducing administrative corruption financially studing analytcal analysts of the same man from the upper leaders in iraqi Organizations
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The Organizational Transparency is regarded one of the effective means in the attempts of the restoration and working to prevent the corruption and reduce the negative managerial economic social and political effects.

Accordingly, this study aims at importance of performing an explorative analytical study in order to stand on the effect of the Organizational Transparency in the reduction of environment of Iraqi Organizations.

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Publication Date
Mon Dec 20 2021
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
MOLECULAR CHARACTERIZATION OF ANISAKID NEMATODES HYSTEROTHYLACIUM SPECIES FROM JAPANESE THREADFIN BREAM NEMIPTERUS JAPONICUS (BLOCH, 1791) (PERCIFORMES, NEMIPERIDAE) FROM IRAQI MARINE WATER FISH
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The present study provides a new insight into valuable information on the diverse structure of the Anisakid population and discusses the limited species richness in the Nemipterus japonicus (Bloch,1791) (Perciformes, Nemiperidae). The fishing area consists of various locations in the Arabian Gulf (29°58 0 33 00 N48°28 0 20 E). A total of 315 marine fish were examined, (n=287) were infected. Larval stages (n= 763) encysted within the mesenteries peritoneum and viscera of fish organs were isolated, with a prevalence of 91.11% of infection and, the intensity was 2.65. Molecular analysis was carried out on thirty individuals who have examined the morphology and showed some appearance differences, by amplifying internal transcribed spacers

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Mon Mar 09 2015
Journal Name
Monthly Notices Of The Royal Astronomical Society
A reliable iterative method for solving Volterra integro-differential equations and some applications for the Lane–Emden equations of the first kind
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Publication Date
Thu Mar 31 2022
Journal Name
Psychological Science
The health and social repercussions of the epidemic crisis (Covid-19) on women (An exploratory study for some private universities - Baghdad / Karkh)
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The current research aims to first - reveal the social repercussions of COVID-19 on women A - The impact of the epidemiological crisis on the social structure of the family B - Psychological and social pressures that women are exposed to during the Covid pandemic C - Social isolation resulting from the injury of a member Second - Understanding the health consequences of COVID-19 on women A- Mechanisms of differentiation in the treatment of Covid-19 treatment, home or hospital As for the limits of the research, the current research is determined by some private universities of students, female employees and teaching staff in Karkh district, which number eight (Al-Hikma, Al-Farahidi, Al-Farabi, Tigris, AlTurath, Al-Rashid, Al-Mashreq, Al-Nuso

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Publication Date
Fri May 05 2023
Journal Name
International Journal Of Professional Business Review
The Effect of Emotional Intelligence on Manager Performance: a Field Study in the General Authority for Irrigation and Reclamation Projects in Baghdad
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Purpose: the purpose of this study is to investigate how managers working for the General Authority for Irrigation and Reclamation Projects react to the impact of Emotional Intelligence (EI) on their performance.   Theoretical framework: The current study includes an intellectual framework on two variables, namely EI and Manager Performance (MP), because it is essential to investigate the relationship between these two variables and the impact of EI on MP.   Design/methodology/approach: The research problem is that a manager's capacity to make wise decisions about their work or interactions with subordinates is diminished when they have inadequate EI. The questionnaire is used as a tool for gathering data for the study, and the st

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Publication Date
Thu May 14 2020
Journal Name
Journal Of Planner And Development
Property ownership and its implications for urban development The Case study (the development project of the Rashid camp for housing in Baghdad)
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        Of the importance of the concept of ownership of real estate as the basic basis from which various projects are launched in various economic, tourism, and urban areas .... The need to research the diagnosis of real estate reality went astray in the difficulties, which played a decisive role in the process of urban development.

 

 This leads us to the research problem of the difficulty of implementing urban development plans in many cases due to the absence of a clear methodology for organizing and modernizing the ownership of real estate and its coordination with the management of urban land and to achieve the objective

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Thu Aug 06 2009
Journal Name
Dirasat
Geneses of the zinc-lead – barite deposits in the Northern Iraq: ore mineralogy, geochemistry, fluid inclusions, lead isotopes and sulfur isotopes implicatiuons
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Sat Jun 18 2022
Journal Name
Sciencescholar Publication
Logical reasoning skills according to Piaget's model for chemistry students in the college of education for pure sciences Ibn al-Haytham in
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Abstract---The aim of the current research is to identify the level of logical reasoning skills in chemistry students at the Faculty of Education for Pure Sciences/ Ibn Al-Haytham for the academic year (2021-2022). The differences in their level of skills according to the gender variable (males and females) and the academic stages (first- second - third - fourth). The descriptive approach was adopted because it corresponds to the nature of the research objectives. The research sample consisted of (400 )students selected in a relatively random stratified way. The researcher constructed a logical reasoning test, which includes (6) sub-skills , which is (proportional - probabilistic- synthetic- deductive- logic- variable adjustment). The psych

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Publication Date
Wed May 01 2024
Journal Name
Baghdad Science Journal
Synthesis, Spectroscopy and Biological Activity Study of Some New Complexes with Schiff Base Derived From Malonic Acid Dihydrazide with 2-pyridine Crboxaldehyde
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Publication Date
Mon Dec 05 2022
Journal Name
Baghdad Science Journal
Heavy Metal Complexes of 1, 2, 3-Triazole derivative: Synthesis, Characterization, and Cytotoxicity Appraisal Against Breast Cancer Cell Lines (MDA-MB-231)
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     New chelating ligand derived from triazole and its complexes with metal ions Rhodium, Platinum and Gold were synthesized. Through a copper (I)-catalyzed click reaction, the ligand produced 1,3-dipolar cycloaddition between 2,6-bis((prop-2-yn-1-yloxy) methyl) pyridine and 1-azidododecane. All structures of these new compounds were rigorously characterized in the solid state using spectroscopic techniques like: 1HNMR, 13CNMR, Uv-Vis, FTIR, metal and elemental analyses, magnetic susceptibility and conductivity measurements at room temperature, it was found that the ligand acts as a penta and tetradentate chelate through N3O2, N2O2, and the geometry of the new complexes are identified as octahedral for (Rh & Pt) complexes a

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