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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 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
Sat Jun 15 2019
Journal Name
Journal Of Baghdad College Of Dentistry
The accuracy of cone-beam computed tomography in the evaluation of boney support of teeth among patients with a unilateral cleft of lip and palate among IraqiPopulation
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Background: To evaluate the bony supports of the teeth adjacent to the area of cleft in patient with unilateral cleft lip and palate and to compare these measurements with the measurements of the same teeth in non-cleft side by using CBCT. Materials and methods: The CBCT scans of 30 patients having cleft lip( unilateral) and palate(unilateral), were analyzed and the measurements of the alveolar bony support for teeth that are adjacent to the cleft area were measured with those teeth located on opposite side (non- clef) side. For each tooth, the measurements will taken for the distance between the( cementoenamel junction) (CEJ) and the bony crest (AC) at the( buccal area) was measured and the thickness of the buccal plate At zero, one, tw

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Publication Date
Sun Dec 01 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The interactive relationship between the dimensions of the requirements of economic intelligence and the strategic success of banks: Applied research on a sample of Iraqi private banks
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The aim of this research is to demonstrate the nature of the interactive relationship between the dimensions of the requirements of economic intelligence Represented by(Administrative and regulatory requirements, human requirements, and technical requirements) The strategic success of banks is represented by (Customer satisfaction, customer confidence, quality of service, growth) In three of the Iraqi banks own bank(Middle East Iraqi Investment, Al Ahli Iraqi, Gulf Commercial), The questionnaire was adopted as a tool for collecting data and information Of the sample (85) Who are they(Director of the Commissioner, M. Director Plenipotentiary, Director of Department, Director of Section, M. Section Manager, Division Officer, Unit Officer),

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Publication Date
Sat Dec 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
Immunohistochemical expression of endocan, as a marker of assessment of angiogenic potential in benign vascular lesions (hemangioma, lymphangioma and lobular capillary hemangioma) of head and neck region
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 BACKGROUND: Vascular tumors are a heterogeneous group of diseases with biological behavior ranging from a hamartomatous growth to frank malignant. The pathophysiology of lymphangioma, vascular malformation and hemangioma is interconnected, blood vessels known to be the site of origin of hamartomas, venous malformations and some neoplasms as benign, tumor-like growth of vessels (hemangiomas). Angiogenesis is the process of formation of new blood vessels from an existing structure.

Aims of study Assessment of angiogenic potential in benign vascular lesions (hemangioma, lymphangioma and lobular capillary hemangioma) of head and neck region.

 Materials and Methods: Twenty-two formalin-fixed paraffin-embedd

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Publication Date
Sat Oct 01 2022
Journal Name
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The evolution of the press image in the Iraqi press (An analytical study of the pictures of the first page of Al-Sabah newspaper for the year)
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This research sheds light on the development that has occurred on the use of press pictures in the Iraqi press by analyzing the form and content of the images used in (Al-Sabaah) newspaper for the 2012 model. The researcher's interest in this topic for what represented by the press picture of a way to highlight and attract the reader's attention to the substance journalist who represents the goals behind the newspaper publishing.

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Mon Aug 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
Evaluating the level of organizational commitment and its relationship to discipline doctors: an analytical study of the opinions of a sample of doctors in Teaching Remade Hospital
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The aims of this reserch is identify  evaluate the organizational commitment level of (emotional, standard, continuous) and the level of discipline dimensions (functional duties, professional responsibility and ethics) for medical doctors in Ramadi Teaching Hospital due to their relationship with the organization effectiveness the level of completion work and the importance of the expected results in the field respondent

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Fri Jul 01 2016
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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
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Wed May 05 2021
Journal Name
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The Role of Chemistry of the Oil-Field Water in the Distribution of Reservoir Pressures: A Case Study of Mishrif Reservoir in the Southern Oil-Fields, Iraq
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Mishrif Formation is the main reservoir in oil-fields (North Rumaila, South Rumaila, Majnoon, Zubair and West Qurna) which located at Basrah southern Iraq. The Inductively coupled plasma-Mass spectrometer (ICP-MS) was used for the water chemistry analysis and Scanning Electron Microprobe (SEM) for the purpose of mineralogy diagnosis. A weak acidic water of salinity six-time greater than seawater plays a role in generating the formation pressure and controlling the fluid flow. The potentiometric subsurface maps were modeled and the direction of super-pressure sites that are of a great importance in the oil exploration were marked to pay attention during future drilling.

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Publication Date
Wed Jun 19 2019
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Effect Wisdom Management in Defferentiation Strategy for Service Operations Exploratory: Search of the Views of A Sample of the Officials in the General Establishment of Civil Aviation
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Today, the success or failure of organizations depends to possess the wisdom of their managers promised that the key to organizational success of the business environment, making the right decisions, and create the ability to work and think towards discrimination of products and services the organization . Seek this research to investigation the relationship between the wisdom management and differentiation strategy for service operations . It was a test of that relationship in light of the results of the analysis of the data collected through the questionnaire distributed on a sample from (98) Director Mangers, head of department and head of division in  the General Establishment of Civil Aviation . The research used descriptive st

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Publication Date
Sat Feb 01 2020
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The role of merger in creating differences in the profitability of companies Analytical research between a sample of subsidiaries to the Iraqi Ministry of Industry and Minerals
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The research aims to identify the impact of the merger of the companies affiliated to the Ministry of Industry and Minerals on their financial profitability since the companies before the merger suffered a rise in losses and the deficit reached very high levels that affected its overall performance and even on the morale of workers as losses are increasing and solutions Efficiency is absent. The problem stems from knowing the impact of the merger on the profitability ratios of the companies. The research field was represented by the companies affiliated to the Ministry of Industry and Minerals (21) companies, while the research sample reached (6) companies after the merger (14) companies before the merger, was based on data The f

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