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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 Jan 01 2018
Journal Name
Journal Of Cosmetics, Dermatological Sciences And Applications
Treatment of Kaposi’s Sarcoma by Combination of Zinc Sulfate and Propranolol
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Mon Jun 30 2014
Journal Name
Al-kindy College Medical Journal
Efficacy of atorvastatin in treatment of Iraqi obese patients with hypercholesterolemia
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ABSTRACTBackground: dyslipidemia plays a crucial rule in the development of cardiovascular disease, which has become the leading cause of death in most developed countries as well as in developing countries (1). The effects of reducing low density lipoprotein – C (LDL-C) concentrations on the prevention of cardiovascular events and stroke have been well reported in many clinical trials.Objectives: Evidence supports the use of statins for lipid modifications in the primary prevention of coronary artery disease, morbidity and mortality. This study aims to determine the effectiveness of atorvastatin in treating dyslipidemia in Iraqi obese patients.Methods: 200 overweight and obese patients with hypercholesterolemia, according to NCEP ATP

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Publication Date
Fri Jun 03 2022
Journal Name
Journal Ofxi'an University Of Architecture & Technology
Extent of mathematics teachers' appreciation of the mathematical problem `multiple solutions
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Aims to find out the (Extent of mathematics teachers' appreciation of the mathematical problem `multiple solutions) Research sample consisted of (100) mathematics teachers distributed on the General Directorates of Education in Baghdad (Rusafa 1/2/3) and (Karkh 1/2/ 3) There was two research approach which are: The first - two different answers of students to the same issue where teachers must assess each answer and explain which one the teacher will accept and why? The second - Different solutions of students' to the same issue, including wrong answers , Teachers should correct the answers and give them final grades (0-10). Descriptive and analytical Approch was used in this research methodology And zero hypotheses, which are as f

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Publication Date
Tue Jun 14 2022
Journal Name
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Representations of puns in the cover designs of Der Spiegel magazine
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 Pun concept the design discourse for the cover of magazines the researcher chose the German magazine Der Spiegel as a model for that, as the research problem was manifested by the following question: What are the representations of puns in the covers of the German magazine (Der Spiegel)? The researcher has identified four chapters for this study as follows: The first chapter is devoted to research procedures, and the theoretical framework, which is like the second chapter, included the literature related to the topic of research according to the two interlocutors. A review of the concept of pun in the field of typographic design and the functions that puns achieve in that field, leading to the third chapter, which included the analysis

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Study of the Factors Affecting the Efficiency of Reverse Osmosis Process
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Thu Oct 10 2024
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Pakistan Journal Of Criminology
The Role of Environmental Bonds in the Settlement of Environmental Debts
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The concept of environmental debt, which has several dimensions, emerged in the nineties. One of these dimensions is spatial, referring to the debts that southern countries sustain due to the extraction of natural resources and environmental damage inflicted upon northern countries. Another dimension, the temporal dimension, concerns the environmental debts that current generations owe to their predecessors. That means past generations are culpable for overuse of natural resources and mismanagement. The debt issue is complex, despite many mechanisms to resolve it. Most important are the recently introduced environmental bonds, an important step forward in the field of sustainable financing of environmental debts.

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Publication Date
Tue Oct 02 2018
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Iraqi Journal Of Physics
Effect of chelating agents on removal of 137Cs from contaminated soil
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In the present research, the chemical washing method has been selected using three chelating agents: citric acid, acetic acid and Ethylene Diamine Tetraacetic Acid (EDTA) to remove 137Cs from two different contaminated soil samples were classified as fine and coarse grained. The factors that affecting removal efficiency such as type of soil, mixing ratio and molarity have been investigated. The results revealed that no correlation relation was found between removal efficiency and the studied factors. The results also showed that conventional chemical washing method was not effective in removing 137Cs and that there are further studies still need to achieve this objective.

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Publication Date
Sun Dec 01 2019
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Analysis of Prosthetic Running Blade of Limb Using Different Composite Materials
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Prostheses are used as an alternative to organs lost from the body. Flex-Foot Cheetah is considered one of the lower limb prostheses used in high-intensity activities such as running. This research focused on testing two samples of Flex-Foot Cheetah manufactured of two various materials (carbon, glass) with polyester and compare between them to find the foot with the best performance in running on the level of professional athlete. In the numerical analysis, the maximum principal stress, maximum principal elastic strain, strain energy; finally, the blade total deformation were calculated for both feet. In experimental work, the load-deflection test was done for foot to calculate the bending the results were very close to

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THE EFFICIENCY OF GUM-SILICA CMPOSITE FOR REMOVING OF WASTEWATER TURBIDITY
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A novel mixed natural coagulant has been developed to remove sewage pollutants and heavy metals from Qanat- al- Jayesh by using low cost adsorbent natural materials. In these materials, significant interaction contains Arabic gum mixed with extracted silica from rice husk ash (natural coagulants) by the Batch device approach, using two variables, pH values ranging from 5-8 and contact times between 0.25-5 hrs. All wastewater samples were collected after treatment by adsorbents and examined for determination of residual heavy metal concentrations: Pb, Ni, Zn and Cu by atomic absorption spectroscopy (AAS), turbidity, pH, total dissolved salts (TDS), electrical conductivity (EC) and total salinity (TS). The results obtained indicate Th

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The main idea of this paper is to define other types of a fuzzy local function and study the advantages and differences between them in addition to discussing some definitions of finding new fuzzy topologies. Also in this research, a new type of fuzzy closure has been defined, where the relation between the new type and different types of fuzzy local function has been studied

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