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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
Sun Dec 31 2017
Journal Name
College Of Islamic Sciences
Sections of beliefs and area of endeavor
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Research summary

 


The researcher in theological sects finds that the controversial issues between the owners of the sects are many, filled with the books of the sects, articles and creeds, and when examining these books it became clear to us that the dispute is related, some of it is related to the meaning and some of it is related to the words and it is many, explained to us by rhetorical terminology such as guidance and delegation, Interpretation and others, and part of it is what is called the verbal disagreement, and sometimes it is by using common possible expressions of truth and falsehood, as in the saying of the Kharijites, “The judgment is only for God,” and some of it is related to something outside th

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Publication Date
Sun Dec 30 2012
Journal Name
Al-kindy College Medical Journal
Evaluation of Management of Closed Spinal Injury
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Objectives: to evaluate the role of conservative, decompression, spine fixation in management of closed spinal injury.
Methods: The study was conducted at Specialized Surgical hospital and Al-Kadhemayia Teaching Hospital, in the period between July 2003 and July 2005.The study included 61 patients categorized Into many groups according level of vertebral injury (cervical, cervicodorsal, dorsal, dorsolumbar, Lumbar and lumbosacral), type of injury (compressed fracture, burst fracture and fracture dislocation) And according the severity into three groups as G1( complete motor paralysis and sensory loss ) G2 ( complete motor paralysis and incomplete sensory loss) and G3 ( incomplete motor paralysis And incomplete sensory loss ).The metho

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Publication Date
Sat Mar 01 2008
Journal Name
Iraqi Journal Of Physics
Study of Optical Properties of HgTe Films
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Alloy of (HgTe) has been prepared succesful in evacuated qurtz ampoule at pressure 4×10-5torr, and melting temperature equal to 823K for five days. Thin films of HgTe of thickness 1μm were deposited on NaCl crystal by thermal evaporation technique at room temperature under vacuum about 4×10-5torr as well as investiagtion in the optical porperties included (absorption coefficient , energy gap) of HgTe films and The optical measurements showed that HgTe film has direct energy gap equal to 0.05 eV. The optical constants (n, k, εr, εi) have been measured over will range (6-28)μm.

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Publication Date
Tue Sep 30 2008
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Optimization of Biochemical Treatment of Tannery Wastewater
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The present work is concerned with the finding of the optimum conditions for biochemical wastewater treatment for a local tannery. The water samples were taken from outline areas (the wastewater of the chrome and vegetable tannery) in equal volumes and subjected to sedimentation, biological treatment, and chemical and natural sedimentation treatment.
The Box-Wilson method of experimental design was adopted to find useful relationships between three operating variables that affect the treatment processes (temperature, aeration period and phosphate concentration) on the Biochemical Oxygen Demand (BOD5).
The experimental data collected by this method were successfully fitted to a second order polynomial mathematical model. The most fa

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Publication Date
Wed Dec 01 2010
Journal Name
Al-khwarizmi Engineering Journal
Evaluation of Mechanical Properties of Particulate Composites
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A series of experiments have been taken out to test the validity of the effect of Aluminum hydrate on its interaction with Aluminum during sintering of aluminum metal matrix. The approach has been shown to be valid and several compositions have been fabricated. The alumina hydrate particle size and the amount of alumina hydrate in the composites are also shown to have an influence on the extent of densification.

The densities for all sintered specimens were measured. It was found that density increases as compaction pressure increases, the density decreases as particles size increases. At 400 MPa there is an optimum particles size which is (90-125) µm to reach maximum density and the density decreases as volume fraction increase

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Publication Date
Wed Nov 07 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Assessment of Types of Violence among Adolescents
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Objective(s): To assess the types of violence among adolescents in Baghdad City.
A descripƟve study which was using the assessment approach was conducted on purposive sample of 60 parents of
adolescent for identify types of adolescents violence in their families, was selected according to specific criteria for
participating in health education program towards adolescents' violence control in Baghdad city.
Methodology: A questionnaire was constructed for the purpose of the study. It was consisted of two parts; the first
part which included the parents' demographic characteristics for parents (sex, age, educational level and socioeconomic
status); the second part included types of adolescent violence that reported by par

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Publication Date
Wed Mar 01 2023
Journal Name
Baghdad Science Journal
Stability of Complement Degree Polynomial of Graphs
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     A graph is a structure amounting to a set of objects in which some pairs of the objects are in some sense related. The objects correspond to mathematical abstractions called vertices (also called nodes or points) and each of the related pairs of vertices is called an edge (also called link or line). A directed graph is a graph in which edges have orientation. A simple graph is a graph that does not have more than one edge between any two vertices and no edge starts and ends at the same vertex.  For a simple undirected graph G with order n, and let  denotes its complement. Let δ(G), ∆(G) denotes the minimum degree and maximum degree of G respectively. The complement degree polynomial of G is the polynomial CD[G,x]= , where C

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Publication Date
Tue Feb 01 2022
Journal Name
Baghdad Science Journal
Effect of the Concentration of Copper on the Properties of Copper Sulfide Nanostructure
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Nanoparticles of copper sulfide have been prepared by simple reaction between using copper nitrate with different concentrations ratio 0.1, 0.3, and 0.5 mM, thiourea by a simple chemical route. The prepared Nano powders have been deposited onto glass substrates by casting method at 60°C. The structure of the product Nano- films has been studied by x-ray diffraction, where the patterns showed that all the samples have a hexagonal structure of covellite copper sulfide with the average crystalline sizes 14.07- 16.51 nm. The morphology has been examined by atomic force microscopy, and field emission scan electron microscopy. The AFM images showed particles with almost spherical and rod shapes with average diameter sizes of 49.11- 90.64 nm.

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Publication Date
Thu Oct 18 2018
Journal Name
Journal Of Economics And Administrative Sciences
Effect of Attitudes in the ethics of the public job of the individual
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Attitude is an important subject that has attracted researchers and thinkers in organizational theory and organizational behavior because of its great importance in various field studies. Field evidence suggests that individuals in their daily lives or careers respond to specific events through a set of internal tendencies Internal tendencies are negative or positive and systematic. These trends tend to be invisible, not limited to certain boundaries, and involve a significant number of individuals within organizations or society.

 The research aims to identify the impact of trends in the ethics of public service workers for individuals, through a sample of (72) doctors and (60) administrative staff

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Publication Date
Thu Nov 01 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Assessment of the psychological domain of the quality of life for infertile men
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Abstract A descriptive correlation study which was utilizing an assessment approach, was carried out from November 19th, 2002 through April 30, 2004 in order to assess the psychosocial domain of the quality of life for the infertile men. A purposive sample of (200) men with infertility was selected from the High Institute for Embryo Research and Infertility Treatment and Alsamaraee Hospital in Baghdad city. A questionnaire was adoapted and developed of the World Health Organization quality of life scale for the purpose of the study. The questionnaire (WHOQOL) (1998) Reliability and validity of the questionnair

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