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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 Aug 31 2015
Journal Name
International Journal Of Advanced Research
On instability of zero solution of some types of forth order
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The purpose of this paper is to study the instability of the zero solution of some type of nonlinear delay differential equations of fourth order by using the Lyapunov-Krasovskii functional approach; we obtain some conditions of instability of solution of such equation.

Publication Date
Mon Jun 01 2015
Journal Name
International J. Of Math. Sci. & Engg. Appls
On instability of zero solution of some types of fifth order
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The purpose of this paper is to study the instability of the zero solution of some type of nonlinear delay differential equations of fifth order with delay by using the Lyapunov-Krasovskii functional approach, we obtain some conditions of instability of solution of such equation.

Publication Date
Fri Jun 15 2018
Journal Name
Преподаватель Xxi век
COMPARATIVE ANALYSIS OF TYPES OF METAPHORS OF RUSSIAN AND ARABIC LANGUAGES
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Metaphor is one of the most important linguistic phenomena of the artistic text, as it is the expression of the author’s emotions and evaluations, the result of a deep inner transformation of the semantic words and visual means of reflecting the national culture of each people. This paper examines the concept of linguistic metaphors and analyzes its types in the Russian and Arabic linguistics, provides a comparative analysis of metaphors in Russian and Arabic — all this allows to conclude that metaphorization is characteris- tic of different parts of speech. In the Russian language stylistic differentiation of the metaphors expressed more than in Arabic, so translation of many “sty- listic” metaphors from Russian into Arabic due to

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Publication Date
Mon Oct 22 2018
Journal Name
Journal Of Economics And Administrative Sciences
Relationship of Communities of practice in adoption of, Strategic Change choices
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The research (Relationship of Communities of practice in adoption of, Strategic Change choices) aims to diagnose and interpretation of correlation nature between Communities of practice deportation (participation and spreading knowledge, confidence, social capital build) deportation strategic change choices (reengineering business process, business re-structuring, business innovation) in construction companies in the Iraqi Ministry of Construction and Housing, the research tested 4 construction companies working in investing sector in Iraq, the research applied on a sample of 102 persons who participated in Communities of practice distributed in several administrative levels (directors, division directors, projec

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Publication Date
Mon Oct 01 2012
Journal Name
Al–bahith Al–a'alami
Technical Construction of Advertisements in Radio of the Republic of Iraq
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Studies and scientific research conducted in the field of communication have shown that broadcasting has a clear impact on the ideas, attitudes and behavior of the masses if it is better used in making the media message studied.

The role of this means is not only to present opinions and ideas, but also to influence trends by supporting or changing them. This is of course a matter for the nature of the content in terms of its formulation and the way it is prepared and presented. The power and appeal of a radio message is not complete by simply creating content without creating a distinctive design; and to what extent this content depends on the logic and psychology of persuasion.

The conviction of the cont

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Publication Date
Thu Sep 01 2022
Journal Name
Neuroquantology
Evaluation of using of square flap in treatment of Postburn Contracture
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Background: One of the most common problems that encountered is postburn contracture which has both functional and aesthetic impact on the patients. Various surgical methods had being proposed to treat such problem. Aim: To evaluate the effectiveness of square flap in management of postburn contracture in several part of the body. Patients and methods: From April 2019 to June 2020 a total number of 20 patients who had postburn contracture in various parts of their body were subjected to scar contracture release using square flap. The follow up period was ranging between 6 months to 12 months. Results: All of our patients had achieved complete release of their band with maximum postoperative motion together with accepted aesthetic outcome. A

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Publication Date
Sun Jun 03 2012
Journal Name
Baghdad Science Journal
Study of Some Epidemiological Aspects of Giardiasis in North of Baghdad
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Different factors have been examined to be related with the prevalence of Girdiasis in the north of Baghdad in human beings which were (gender, age , occupation ,family size,faecal status and presence of domestic animals) during the period from the beginning of April 2009 till the end of March 2010. This study revealed that the total rate of infection in human being was 11.66% , and no significant differences (p?0.05) were noticed between male and female as their rates of infection were 52.32% and 47.68% respectively , as well as no significant relation was observed between faecal status and the rate of infection, the percentage of positive cases in diarrheal patients was higher than the non diarrheal patients who were 74.41 and 25.59 respe

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Publication Date
Sat Jun 01 2013
Journal Name
Journal Of Economics And Administrative Sciences
Scope of using accounting of responsibility under contition of public badget
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Abstract

  The public budget in Iraq is still prepared according to the traditional base that allocates the  amounts of budget the current year based on the budget of previous year with an increase in estimations with random proportions without connecting the input (financial, human resources and asset )with their output (quantitatively and qualitatively)this caused waste and lose in the available resources therefore the output of budget showed be adapted is such a way that achieving connection between its input and output and to be appropriate with the organizational structure of the state without intrinsic change in its work .this may be realized by adopting the accounting of

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Publication Date
Mon Jun 01 2015
Journal Name
Journal Of Economics And Administrative Sciences
Theories of the structure of modern finance : practical application of pecking order theory and the life cycle of the company/analytical research of asmple of foreign companies
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 Is the subject of the financial structure of the most important topics for which she received the interests of scientific research in the field of financial management , as it emerged several theories about choosing a financial structure appropriate for the facility and behavior change funding them , and in spite of that there is no agreement on a specific theory answer various questions in this regard , and a special issue of the financial structure optimization.

The objective of the research was to identify the most important theories of the structure of modern financial theory has been to focus on the capture of financial firms in two different stages of their life cycle , so-called growth and ma

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Publication Date
Tue Sep 01 2009
Journal Name
Journal Of Economics And Administrative Sciences
Evaluating the quality of educational services according to the modified Servqual modelStudy of a sample of students of the Faculty of Management and Economics / University of Baghdad
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The research aims to apply a modified SERVQUAL model to evaluate the quality of the educational services via conducting exploratory research for students from the College of Administration and Economics- Department of Business Administration- Evening studies at the University of Baghdad. Questionnaire of two parts was distributed to a sample of (72) students out of (720) students of the 2nd.,3rd. and 4th. year in the beginning of the second semester of the year 2008-2009 to measure the expectations and perceptions to the quality of the educational services. Five major dimensions were analyzed to see the gaps for (22) variables. The study concluded that there were (13) variables confirmed that the

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