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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 May 06 2010
Journal Name
Dirasat, Pure Sciences
A Study of the Effects of the Solar Cycle 22, on the Critical Frequencies of F1 Layer over Baghdad
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This paper aims to study the effects of the long term solar activity on the critical frequencies of ionospheric F1 layer over Baghdad city, during the solar cycle 22, within (1988- 1995). It is found that the critical frequency of this layer is closely related to the sunspots number during the years of the solar cycle 22, at a middle latitude region of the world. The study discussed the effect of sunspot numbers and solar events on the electron densities of F1 layer, which is the most important ionospheric parameter.

Publication Date
Fri Dec 15 2017
Journal Name
Journal Of Baghdad College Of Dentistry
The Effect of Addition of Zirconium Nano Particles on Antifungal Activity and Some Properties of Soft Denture Lining Material
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Background Microorganisms and fungal growth especially Candida albicans, on soft denture lining material are the most common problem which can lead to chronic mucosal inflammation. The aim of this study was to evaluate the effect of zirconium nanoparticles into acrylic-based heat cured soft denture lining material against Candida albicans, and the amount of zirconium ion release of soft liner/ZrNPs composite. Furthermore, evaluate shear bond strength after ZrNPs addition to soft liner. Materials and methods: Zirconium nanoparticles were added into acrylic-based soft denture liner in various percentages (1%, and 1.5% by weight). Two hundred and fifty specimens were arranged and isolated into four groups as per the test to be done The antifu

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Publication Date
Sat Aug 01 2020
Journal Name
Key Engineering Materials
Compressive Strength Performance of Reactive Powder Concrete Using Different Types of Materials as a Partial Replacement of Fine Aggregate
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Reactive Powder Concrete (RPC) can be incorporate as a one of the most important and progressive concrete technology. It is a special type of ultra-high strength concrete (UHSC) that’s exclude the coarse aggregate from its constitutive materials. In this research an experimental study had been carried out to investigate the effect of using three types of materials (porcelain aggregate) and others sustainable materials (glass waste and granular activated carbon) as a partial replacement of fine aggregate. Four percentages had considered (0, 10, 15 and 20) % to achieve better understanding for the influence of these materials upon the compressive strength of RPC. Four curing ages had included in this study, these are; 7, 28, 60 and

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Publication Date
Mon Dec 05 2022
Journal Name
Baghdad Science Journal
Effect of Secondary Metabolite Crude of Metarhizum anisopliea Fungus on the Second Larval Stage of the Housefly Musca domestica
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         The house flies Musca domestica )Diptera:musidae) are the primary carrier of many pathogens such as cholera, typhoid, anthrax, and others. The use of chemical pesticides as a basic method of control leads to many problems at the environmental and health level. The use of safe alternatives to chemical pesticides has become an urgent necessity. The research aims to find biological alternatives that are environment-friendly and non-pathogenic to humans in controlling house flies through the possibility of extracting and diagnosing some secondary metabolites produced by the fungus Metarhizium anisopliae and testing their effects on the second larval stage of house flies using different treatment methods that include

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Publication Date
Sat Aug 01 2020
Journal Name
Key Engineering Materials
Compressive Strength Performance of Reactive Powder Concrete Using Different Types of Materials as a Partial Replacement of Fine Aggregate
...Show More Authors

Reactive Powder Concrete (RPC) can be incorporate as a one of the most important and progressive concrete technology. It is a special type of ultra-high strength concrete (UHSC) that’s exclude the coarse aggregate from its constitutive materials. In this research an experimental study had been carried out to investigate the effect of using three types of materials (porcelain aggregate) and others sustainable materials (glass waste and granular activated carbon) as a partial replacement of fine aggregate. Four percentages had considered (0, 10, 15 and 20) % to achieve better understanding for the influence of these materials upon the compressive strength of RPC. Four curing ages had included in this study, these are; 7, 28, 60 and

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Publication Date
Wed Apr 01 2020
Journal Name
Iraqi Journal Of Agricultural Sciences
Study of different factors effected in production of dextranase enzyme from a local isolate of b. Subtilis Z2 bacteria
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Publication Date
Sat Dec 15 2018
Journal Name
Journal Of The College Of Education For Women
The Reasons for the Behavior of Bullying school Students in the first grade average from the point of view of teachers and teachers and methods of modification
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 هدف البحث التعرف الى اسباب سلوك التنمر لدى طلاب الصف الاول المتوسط من وجهة نظر المدرسين والمدرسات واساليب تعديله، واستعمل الباحثان المنهج الوصفي واختيار عينة عشوائية من المدرسين والمدرسات في متوسطة أرض الرافدين ومتوسطة الرحمن للبنين وكان عددهم (46) مدرساً ومدرسة بواقع (32) مدرساً و(14) مدرسة، واعتمد الباحثان الاستبانة أداة للتعرف الى اسباب سلوك التنمر واساليب تعديله، واشارت نتائج البحث الى تنوع اسباب التن

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Publication Date
Sun Sep 05 2010
Journal Name
Baghdad Science Journal
Influence of Indole acetic acid and Tryptophan on production of Vinblastine and Vincristine of Catharanthus roseous callus cells in the accumulation media of In Vitro tissue culture
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This study on the plant of Ain –AL Bason Catharanthus roseous showed the ability of callus cells that is produced by In Vitro culture technique and transformed to the accumulated media (MS 40gm/L sucrose ,2gm/L IAA Indole acetic acid , 0.5gm/L Tryptophan) to produce Vinblastine and Vincristine compounds. Extraction, purification and quantitive determination of Vinblastine and Vincristine compounds using High performance liquid chromatography technique (HPLC)were carried out. The results showed that the highest concentration of Vinblastine and Vincristine compounds were ( 4.653,12.5 (ppm /0.5 dry Wight respectively from transformed callus cells from MS 40 gm /L sucrose , 2 gm / L NAA Naphthaline acetic acid .

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Publication Date
Sun Sep 07 2008
Journal Name
Baghdad Science Journal
The Extent of Homogeneity in the Distribution of Petrophysical Properties that Affecting the Primary and Enhanced Oil Recoveries of Reservoir Rocks in Zubair Formation of South Iraq
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Records of two regionalized variables were processed for each of porosity and permeability of reservoir rocks in Zubair Formation (Zb-109) south Iraq as an indication of the most important reservoir property which is the homogeneity,considering their important results in criterion most needed for primary and enhanced oil reservoirs.The results of dispersion treatment,the statistical incorporeal indications,boxes plots,rhombus style and tangents angles of intersected circles indicated by confidence interval of porosity and permeability data, have shown that the reservoir rocks of Zubair units (LS),(1L) and (DJ) have reservoir properties of high quality,in contrast to that of Zubair units (MS) and (AB)which have reservoir properties of less q

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Publication Date
Fri Jul 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
A reflection of organizational citizenship behaviors in the performance of employees A prospective study of a sample of the teaching staff working in the Degla University College
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Abstract
        This research aims to identify the relationship and the impact of the behavior of organizational citizenship in the performance of employees, as practiced behaviors organizational citizenship substantial role in achieving the objectives of both the organization and its staff at the same time, so it affects a large extent on the characteristics and performance of individuals employees and thus influence the success of the organization as a whole, problem of the research has indicated that there is a clear failure in the study of the impact of the behavior of organizational citizenship in the performance of employees, was chosen

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