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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 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
Thu Feb 01 2024
Journal Name
Baghdad Science Journal
Significance and Conservation of Birds of the Genus of Bee-eater (MEROPS) in Uzbekistan
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The purpose of this article is to identify and evaluate the importance of birds of the genus Merops (European Bee-eater -Merops apiaster and Blue-cheeked Bee-eater -Merops persicus) in Uzbekistan, as well as to develop recommendations aimed at solving some problems associated with its conservation. As a result of the study, in the aspect of biocenotic relations, the natural significance of these species was revealed. The economic value is determined and analyzed in beekeeping farms. From the study of the remains of food contained in the stomachs, throats and nests of M.apiaster, a preliminary list of the main species of the food spectrum has been compiled. Based on the bioacoustic repellent "Korshun-8"

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Publication Date
Sun Dec 07 2008
Journal Name
Baghdad Science Journal
The effect of doping ratio of Cu on the structural properties of CdSe Films
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Films of CdSe have been prepared by evaporation technique with thickness 1µm. Doping with Cu was achieved using annealing under argon atmosphere . The Structure properties of these films are investigated by X-ray diffraction analysis. The effect of Cu doping on the orientation , relative intensity, grain size and the lattice constant has been studied. The pure CdSe films have been found consist of amorphous structure with very small peak at (002) plane. The films were polycrystalline for doped CdSe with (1&2wt%) Cu contents and with lattice constant (a=3.741,c=7.096)A°, and it has better crystallinty as the Cu contents increased to (3&5wt%) Cu. The reflections from [(002), (102). (110), (112), and (201)]planes are more prominen

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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
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
Wed Nov 13 2019
Journal Name
Al-kindy College Medical Journal
Outcome Of Surgical Treatment Of Tuberculosis Of The Spine In Patients With Motor Deficits
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Background: Significant numbers of patients with spinal tuberculosis (TB), especially in developing countries, still present late after disease onset with severe neurological deficits.

Objective:This study was conducted to assess the outcome of surgery in patients with tuberculosis of the spine with motor deficits.

Type of the study: Retrospective study.

Methods: We retrospectively analyzed data obtained in all the patients with severe motor deficits due to spinal TB admitted to and surgically treated in four hospitals in Baghdad/Iraq during the period from January 2012 to January 2014. History, examination, imaging, histological, postoperative, a

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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
Wed Jan 01 2020
Journal Name
Plant Archives
STUDY OF THE EFFECT OF COLD PLASMA ON THE REPRODUCTIVE ENDOCRINOLOGY OF MALE RATS
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Cold atmospheric plasma (CAP) is used widely in medical and biological fields because of non-thermal effected. Direct application of plasma is preferred in medical functions, so, direct application of cold plasma has obtained by the floating electrode dielectric barrier discharge (FE-DBD) system. The purpose of this paper to review the effect of (CAP) on the reproductive hormones (testosterone, LH, E2, progesterone, for male rats. The study appeared that no significant effect on E2 and progesterone hormone for all time of exposure, besides this significant difference in LH hormone (P<0.05) at 15 sec, (P<0.0001) at 30, 90 sec and (P<0.001) at 60 sec of exposure to plasma. Added to that significant difference (P<0.01) at 15, 30, 60 sec and no

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Publication Date
Wed Jun 07 2023
Journal Name
Journal Of Educational And Psychological Researches
Selective Visual Attention among Students of Colleges of Education At The University Of Mosul
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The research aims to identify the level of selective visual attention among students of the faculties of education at the University of Mosul. To achieve the goal of the research, the researchers chose a stratified random sample of students from the faculties of education at the University of Mosul for the academic year (2020-2021). The sample size was (652) students from the scientific and humanitarian specializations, the second and fourth stages. The researchers developed a test of multiple-choice to measure the selective visual attention, which consisted of (42) items. The results revealed that the students of the faculties of education for human sciences have an appropriate level of selective visual attention. There are statisticall

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Publication Date
Sun Jun 03 2012
Journal Name
Baghdad Science Journal
Approximate Solution of Some Classes of Integral Equations Using Bernstein Polynomials of Two-Variables
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The research aims to find approximate solutions for two dimensions Fredholm linear integral equation. Using the two-variables of the Bernstein polynomials we find a solution to the approximate linear integral equation of the type two dimensions. Two examples have been discussed in detail.

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