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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
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Effect of Gamma Rays on Some Aspects of BiologicalPerformance of Callosobrchus maculatus (Fabricius)and Trogoderma granarium (Everts).
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The effect of gamma rays on males and females ofCallasobruchus maculatus and Trogoderma granarium which were irradiated as 1-3 days old adults was investigated. The results revealed that the percent egg hatch for both pests was zero ,and average number of egg (34.2,21.5) for both pests respectively where their males where irradiated with 0.18 kGy and mated with unirradiated females. While the percent of egg hatch and the average number of egg (zero,21,3) respectively when the females where irradiated with 0.18 and 0.15 kGy and mated to unirradiated males for C. maculatus and T. granarium respectively. Furthermore, the results showed that the percent of eggs hatch and average number of egg was ( zero,22.7) for C. maculatus when both sexes i

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Publication Date
Sun Dec 04 2016
Journal Name
Baghdad Science Journal
The Efficiency of Terpenes Extracts of Eucalyptus Camaldulensis Seed to control Larval Stage of Callosobruchus maculates (Coleoptera:Bruchidae)
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The current study has beenconduced to evaluate the effect of extracted crude terpens at the concentrations of 6,8% of seeds of Eucalyptuscamaldulensison the 4th larval instar oftheCallosobruchusmaculates and the percentage of the cowpea seed germination.The Results showed that the terpens extract of the concentration of 8% increases the mortality rate of the fourth larval instar and it reach to 63.3%, and then decrease of to 26.6,20% at concentration of 6%and forcontrol treatment respectively The percentage of adult emergence reduces to 0% at the concentration of 8% compared with control treatment in which it reach to 66.6%. The extraction atbothconcentrations 6,8% does not affect the germination rate

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Publication Date
Fri Aug 01 2014
Journal Name
Journal Of Economics And Administrative Sciences
The evaluation of the procedures of excution the national strategy of unti - corruption in Iraq (2014-2010)
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    Corruption has become the subject of great interest, and the subject of research and scrutiny in recent years, because of its penetration in all fields of life,  whether these fields are political, economic, social, and administrative. It is one of the biggest challenges and problems that are facing communities. Therefore, this study is focused on the evaluation of measures implementing the national strategy to combat corruption in Iraq.

This study was launched, first because of its intellectual dimensions to ensure a conceptual presentation of the strategy and operational management in general with a special focus on the processes of implementation and control str

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Publication Date
Wed Aug 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
The impact of electronic audit in raising of the independence and professional efficiency of the internal auditor
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The research aims to shed light on the role of E-Audit in raising Independence and professional competence of the external auditor, the study has been applied on a sample of the branches of the Rafidain Bank n have been addressed research topic beside the theoretical, as put forward by the literature of accounting, audit and that the contents of the section first, either the practical side was required to test the hypotheses use form questionnaire, which was distributed to a sample of the external auditors and bankers research sample. He has applied for his part in the search for a standard of independence and professionalism of the external auditor and the factors influencing these standards, and the most import

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Publication Date
Thu Oct 16 2025
Journal Name
Journal Of Baghdad College Of Dentistry
The effect of SOLO and sodium hypochlorite disinfectant on some properties of different types of dental stone
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Background: Dental casts come into direct contact with impression materials and other items that are contaminated by saliva and blood from a patient's mouth, leaving the casts susceptible to cross-contamination. The disinfectant solutions of the impression materials cause various adverse reactions. Therefore, disinfection of dental casts may be effective in preventing cross infection. This study was carried out to evaluate the surface hardness, dimensional accuracy, reproduction of details and surface porosity of type III, type IV and type IV extra hard dental stone after immersion in and spray by using SOLO and Sodium hypochlorite disinfectant solutions. Materials and methods: 240 Stone samples were prepared in rubber rings, A total of 60

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Publication Date
Fri Oct 07 2011
Journal Name
Ibn Al- Haitham J. For Pure & Appl. Sci.
Assessment of the Level of Trace Metals in Commonly Edible Vegetables and Fruits of Baghdad City (Iraq)
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A study was carried out to determine the concentrations of trace metals in vegetables and fruits, which are locally available in the markets of Baghdad-samples of fourteen varieties of vegetables and fruits, belonging to Beta vulgaris, Brassica rapa, Daucus carota, Allium cepa, Eurica sativa, Malva silvestris, Coriandrum Sativum, Trigonella Foenum craecum, Anethum graveolens, Barassica oleracea, Phaseolus vulgaris, citrus reticulata, Py rus malus, and Punica granatum. Analysis for Cd,Pb, Mn, Fe, Co, Ni, Cu and Zn were determined by flame atomic absorption sp ectrophotometry. The results indicated that the Malva silvestris recorded the highest concentrations of Cd and Mn while Allium cepa showed the highest concentrations of Pb and Cu. But E

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Publication Date
Sat Jun 06 2020
Journal Name
Journal Of The College Of Education For Women
Difficulties Facing the Teaching of Writing for Students at College of Education for Women, University of Baghdad
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This research paper attempts to explore problems facing the teaching of written expression among first-year female university students. The focal point behind conducting this research is to show the importance that writing is taking as a skill in learning the language. To achieve this goal, the researcher prepared a questionnaire consisting of 20 items. The sample, whose size is 60 participants, was selected randomly from the department of Arabic, College of Education for Women, University of Baghdad. Through the use of a set of statistical means including weighting means and percentage, the findings revealed that the students face many difficulties in learning writing. The researcher suggested some recommendations, mainly improving the

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Publication Date
Wed Dec 30 2015
Journal Name
College Of Islamic Sciences
Minor fatwas of the star of religion special Khwarizmi (v ....... e) Matters in the Book of Rentals
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Scholars have inherited a tremendous wealth in all sciences and knowledge, especially jurisprudence; therefore, the students of forensic science had to execute this precious heritage, achieving a serious scientific investigation; So I opted for the realization of this part of the Book of Leasing for the small book of fatwas of Yusuf bin Ahmed al-Khasi.

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Publication Date
Tue May 28 2024
Journal Name
Journal Of Optics
Study of the optical properties of aluminum films and the effect of current frequency on plasma parameters
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Publication Date
Fri Jun 15 2018
Journal Name
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Histological and histomorphometric studies of the effects of hyaluronic acid on osseointegration of titanium implant in rabbits
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Background: One of the unique prosthesis for tooth or teeth replacement is the dental implant. Our attempt is using a biomaterial system that is easily obtained and applicable and has the ability to provoke osteoinductive growth factor to enhance bone formation at the site of application. One of these natural polymers is hyaluronic acid. Material and methods: Sixty machined surface implants from commercially pure titanium rod inserted in thirty NewZealand rabbits. Two implants placed in both tibia of each rabbit. The animals scarified at 1, 2 and 4 weeks after implantation (10 rabbits for each interval). For all of animals the right tibia’s implant was control (uncoated) and the left one was experimental (coated with 0.1ml Hyaluro

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