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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
Sat Jul 01 2000
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
UTTILIZATION OF LIPIDS AS SOURCE OF ENERGY DURING HIBERNATION OF RANA RIDIBUNDA PALLAS, 1771
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The aim of this study is to calculate the ene expenditure from fatty substance contents of the
frog. Rana ridibunda during its hibernation. It was found that, almost, all frogs enter
hibernation during the last week of December and emerge from hibernation during the first
week of March. Hence, January and February are considered the hibernation period.
December is the pre-hibernation period and March is the post-hibernation period. The
reduction in percent of body lipid during the hibernation period was 4.8% in males and 7.7%
in females. The reduction in percent of lipid of fat bodies during the hibernation period was
2.758% in males and 0.733% in females.
The calorific value of R. ridibunda lipid amounted to 1233

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Publication Date
Sun Jun 05 2022
Journal Name
Sport Tk-revista Euroamericana De Ciencias Del Deporte
Analytical study of the reality of the application of administrative automation in sports clubs
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The primary objective of this study was to identify the obstacles and problems encountered in the work of sports clubs according to the reality of the application of administrative automation. The present study was conducted in the sports club headquarters of Baghdad within the timeframe of October 2021 to December 2021. In the present study, a descriptive approach was used by the researchers in an analytical style according to the nature of the problem to be studied. The research community of the current study was composed of 100 sports clubs in the governorate of Baghdad. A total of 80 questionnaires were filled by the sample participants, who represented a percentage of 80% of the research community. After processin

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Publication Date
Sun Jun 06 2010
Journal Name
Baghdad Science Journal
Algebraic Coincidence Periods Of Self – Maps Of A Rational Exterior Space Of Rank 2
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Let f and g be a self – maps of a rational exterior space . A natural number m is called a minimal coincidence period of maps f and g if f^m and g^m have a coincidence point which is not coincidence by any earlier iterates. This paper presents a complete description of the set of algebraic coincidence periods for self - maps of a rational exterior space which has rank 2 .

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Publication Date
Tue Apr 01 2014
Journal Name
Journal Of Economics And Administrative Sciences
Re-distribution of income in favor of the poor - theoretical entrance of stagnation treatment
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Research deals the crises of the global recession of the facets of different and calls for the need to think out of the ordinary theory and find the arguments of the theory to accommodate the evolution of life, globalization and technological change and the standard of living of individuals and the size of the disparity in income distribution is not on the national level, but also at the global level as well, without paying attention to the potential resistance for thought the usual classical, Where the greater the returns of factors of production, the consumption will increase, and that the marginal propensity to consume may rise and the rise at rates greater with slices of low-income (the mouths of the poor) wi

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Publication Date
Thu Apr 13 2023
Journal Name
Sustainability
Experimental Study of the Effect of Tack Coats on Interlayer Bond Strength of Pavement
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The performance and lifetime of the flexible asphalt pavement are mainly dependent on the interfacial bond strength between layer courses. To enhance the bond between layers, adhesive materials, such as tack coats, are used. The tack coat itself is a bituminous material, which is applied on an existing relatively non-absorbent surface to ensure a strong bond between the old and newly paved layer. The primary objective of this study was to evaluate the effects of various types of tack coat materials on interlayer bond strength and to determine the optimal application rate for each type. The tack coat types used in this paper were RC-70, RC-250, and CSS-1h. Both laboratory-prepared and field-constructed hot mix asphalt concrete pavements usin

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Publication Date
Tue Feb 05 2019
Journal Name
Journal Of The College Of Education For Women
Spatial contrast of the slums in the unity of the new municipal of Baghdad
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The slums one of the main problem plaguing the city of Baghdad in general and
the unity of municipality of New Baghdad, especially, where the characteristics of the study
area a prominent role in population growth and the emergence of slums where a private,
although the region suffer from the housing crisis is the lack of the number of housing units
compared to the number of families in which, With high land prices and the level of rent
which was accompanied by the absence of the law, which was followed by the year 2003, has
become the study area and one of the most municipalities of the city of Baghdad Contain
slums which took fills abandoned buildings and acquires vacant land agricultural ones and
allocated to d

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Publication Date
Thu Sep 15 2022
Journal Name
Al-adab Journal
Vocabulary of the modern Russian language from the point of view of stylistic diversity
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Сатья посвящена выделению и описанию функциональных стилей русского языка. В работе будет предствлена стилистическая характеристика заимствованной лексики, которая в некоторых случаях заменяет собственно русские слова, что может приводить к затемнению смысла высказывания, эвфемизации его, кроме того, заимствования заполняют определенные стилистические книши, образовавшиеся в связи со структурны

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Publication Date
Tue Oct 30 2018
Journal Name
Al-kindy College Medical Journal
The Effectiveness of Calcaneal Drilling for Treatment of Resistance Cases of Plantar Heel Pain
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Background: Plantar heel pain is a clinical syndrome characterized by pain and tenderness beneath the heel which is typically worse in the morning and improves after the first few steps in the day. It is a common and frequently disabling clinical complaint that may be caused by a broad spectrum of osseous or soft tissue disorders. Objective: To evaluate the effectiveness of an operation of multiple drilling of calcaneum for resistant plantar heel pain syndrome. Methods: During the period from November 2012 to August 2016, 17 patients (17heels) were enrolled in a cohort clinical study at the orthopedic unit in AL-Sheikh Zayed and AlWassity Hospitals. Result: Drilling of the calcaneum is a simple procedure achieving 70.6% cure in resistant as

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Publication Date
Mon Aug 25 2025
Journal Name
Al-fatih Journal
Effect of resistance training on the development of marital some elements of physical fitness
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يشهد العالم تقدما في كافة مجالات الحياة المختلفة وتزداد الحياة صعوبة يوما بعد يوم, ويزداد البحث في كافة المجالات التي تعمل على خدمة الإنسان ولقد طال هذا التقدم النشاط الرياضي ,فقد يكون لتطور التدريب الرياضي وتنوع أساليبه الدور الكبير في تحقيق اللياقة البدنية التي تعد إحدى أهم الأهداف التي يرمي إليها الدرس في كلية التربية الرياضية . واللياقة البدنية تستمد أهميتها من كونها إحدى مكونات اللياقة الشاملة التي بدو

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Publication Date
Thu Jun 15 2017
Journal Name
Journal Of Baghdad College Of Dentistry
A Comparison of Vertical Marginal Fit of different Brands of Translucent Zirconia Crown Restorations
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Background: As the development of zirconia crown using CAD/CAM technology, the usage of full zirconia crown is gradually increased. The aim of this in-vitro study was to evaluate and contrast the vertical marginal fit of single all-ceramic translucent zirconia crowns constructed from different brands translucent zirconia blanks. Materials and Methods: An acrylic resin model of a left maxillary premolar was prepared all around the tooth with (1 mm) depth and 3D scanning to get fifteen STL files, then distributed into three groups (Imes-icor, Whitepeaks and Dental direct), 3D scanning and milling machine by Imes-icor CAD/CAM devise. Marginal gaps along vertical planes were measured at four indentations at the (mid mesial, mid distal, mid bucc

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