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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 Jun 05 2022
Journal Name
Sport Tk-revista Euroamericana De Ciencias Del Deporte
Analytical study of the reality of the application of administrative automation in sports clubs
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The primary objective of this study was to identify the obstacles and problems encountered in the work of sports clubs according to the reality of the application of administrative automation. The present study was conducted in the sports club headquarters of Baghdad within the timeframe of October 2021 to December 2021. In the present study, a descriptive approach was used by the researchers in an analytical style according to the nature of the problem to be studied. The research community of the current study was composed of 100 sports clubs in the governorate of Baghdad. A total of 80 questionnaires were filled by the sample participants, who represented a percentage of 80% of the research community. After processin

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Publication Date
Sun Jun 09 2019
Journal Name
Al-kindy College Medical Journal
The Effectiveness of Calcaneal Drilling for Treatment of Resistance Cases of Plantar Heel Pain
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Background: Plantar heel pain is a clinical syndrome characterized by pain and tenderness beneath the heel which is typically worse in the morning and improves after the first few steps in the day. It is a common and frequently disabling clinical complaint that may be caused by a broad spectrum of osseous or soft tissue disorders.

Objective: To evaluate the effectiveness of an operation of multiple drilling of calcaneum for resistant plantar heel pain syndrome.

Methods: During the period from November 2012 to August 2016, 17 patients (17heels) were enrolled in a cohort clinical study at the orthopedic unit in AL-Sheikh Zayed and Al-Wassity Hospitals.

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Publication Date
Mon May 01 2023
Journal Name
Journal Of Engineering
The Effect of Type of Fiber in Density and Splitting Tensile Strength of SIFCON
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SIFCON is characterized as a construction material of high ductility and very high strength. It is suitable for concrete structures used for special applications. However, the density of SIFCON is much higher than that of Fiber Reinforced Concrete (FRC) due to the need for a large amount of high-density steel fibers. This work examines the split tensile behavior of modified weight slurry infiltrated fiber concrete utilizing a mixture of two types of fibers, steel fiber, and polyolefin fiber. For the investigation, 30 cylinders and 15 cubes were poured. The used volume fraction (V.F) is (6 %) and the use of five series once as each type separately and once a hybrid in proportions of 2/3 polyolefin with 1/3 steel fiber and

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Publication Date
Sat Jun 18 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Isolation of beta-sitosterol and evaluation of antioxidant Activity of Iraqi Campsis grandiflora flowers.
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Campsis grandiflora (Bignoniaceae) is a fast growing deciduous climber, the dried flowers have been used as a carminative, blood tonic, and febrifuge in Chinese traditional medicine. This plant has an anti-inflammatory, anti-oxidant, anti-depressant, and anti-bacterial effect; with a beneficial role in stagnant blood and endometriosis conditions. In this study, the detection of beta-sitosterol in the hexane extract of Iraqi C.grandiflora flowers was performed using thin layer chromatography (TLC) and high performance liquid chromatography(HPLC); while the isolation done by preparative layer chromatography then structure elucidation of isolated compound was done by FTIR and 1HNMR. Furthermore, assessment of th

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Publication Date
Thu Jan 01 2015
Journal Name
Journal Of Engineering
Formal Characteristics of the Architectural Type of contemporary Mosques within the concept of Topology
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Mosques could be considered as one of the most powerful architectural types throughout historical ages. With their highly symbolic formal legacy, Mosques  play an essential role in providing the Islamic city with its special identity. Nevertheless, the advent of digital technology and its ubiquity at different levels of architectural design marked the emergence of new tendencies in the Architecture of Mosques, represented by various models added to the storage of this architectural type. Consequently a review of these tendencies would be needed, aiming at pointing out the formal transformations and new suggested characteristics.

The paper investigates the surviving and the disappearing formal components of&n

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Publication Date
Tue Feb 05 2019
Journal Name
Journal Of The College Of Education For Women
Spatial contrast of the slums in the unity of the new municipal of Baghdad
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The slums one of the main problem plaguing the city of Baghdad in general and
the unity of municipality of New Baghdad, especially, where the characteristics of the study
area a prominent role in population growth and the emergence of slums where a private,
although the region suffer from the housing crisis is the lack of the number of housing units
compared to the number of families in which, With high land prices and the level of rent
which was accompanied by the absence of the law, which was followed by the year 2003, has
become the study area and one of the most municipalities of the city of Baghdad Contain
slums which took fills abandoned buildings and acquires vacant land agricultural ones and
allocated to d

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Publication Date
Thu Jun 18 2015
Journal Name
Journal Of Kerbala University
Effect of Carbamazepine drug on formation of decidual tissue in femal of Mus musculus
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Implantation of blastocyst is considered as a sensitive process in the life of growing embryo. Thus this critical period could be under threat from the harmful effect of many drugs ,among them is the carbamazepine which is used by many women for a treatment of epilepsy . The present experiment was designed to study the effect of this drug on the process of implantation ;especially during the days 7 and 9 of pregnancy. For those purpose 169 pregnant albino mice, of 25 gm weight for each one, were used .The mice were divided into control group given orally normal saline, and treated group given orally carbamazepine with concentration of 15 mg\kg. Samples from pregnant uteri containing the embryos were used. They were first fixed in Boun's sol

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Publication Date
Sat Jul 01 2000
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
UTTILIZATION OF LIPIDS AS SOURCE OF ENERGY DURING HIBERNATION OF RANA RIDIBUNDA PALLAS, 1771
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The aim of this study is to calculate the ene expenditure from fatty substance contents of the
frog. Rana ridibunda during its hibernation. It was found that, almost, all frogs enter
hibernation during the last week of December and emerge from hibernation during the first
week of March. Hence, January and February are considered the hibernation period.
December is the pre-hibernation period and March is the post-hibernation period. The
reduction in percent of body lipid during the hibernation period was 4.8% in males and 7.7%
in females. The reduction in percent of lipid of fat bodies during the hibernation period was
2.758% in males and 0.733% in females.
The calorific value of R. ridibunda lipid amounted to 1233

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Publication Date
Tue Oct 30 2018
Journal Name
Al-kindy College Medical Journal
The Effectiveness of Calcaneal Drilling for Treatment of Resistance Cases of Plantar Heel Pain
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Background: Plantar heel pain is a clinical syndrome characterized by pain and tenderness beneath the heel which is typically worse in the morning and improves after the first few steps in the day. It is a common and frequently disabling clinical complaint that may be caused by a broad spectrum of osseous or soft tissue disorders. Objective: To evaluate the effectiveness of an operation of multiple drilling of calcaneum for resistant plantar heel pain syndrome. Methods: During the period from November 2012 to August 2016, 17 patients (17heels) were enrolled in a cohort clinical study at the orthopedic unit in AL-Sheikh Zayed and AlWassity Hospitals. Result: Drilling of the calcaneum is a simple procedure achieving 70.6% cure in resistant as

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Publication Date
Sat Mar 01 2008
Journal Name
Iraqi Journal Of Physics
The effect of Cu concentration on some of the electrical properties of CdSe films
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The CdSe pure films and doping with Cu (0.5, 1.5, 2.5, 4.0wt%) of thickness 0.9μm have been prepared by thermal evaporation technique on glass substrate. Annealing for all the prepared films have been achieved at 523K in vacuum to get good properties of the films. The effect of Cu concentration on some of the electrical properties such as D.C conductivity and Hall effect has been studied.
It has been found that the increase in Cu concentration caused increase in d.c conductivity for pure CdSe 3.75×10-4(Ω.cm)-1 at room temperatures to maximum value of 0.769(Ω.cm)-1 for 4wt%Cu.All films have shown two activation energies, where these value decreases with increasing doping ratio. The maximum value of activation energy was (0.319)eV f

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