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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
Tue Dec 30 2008
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Cathodic Protection of Copper Pipes Carrying Saline Water in the Presence of Aerobic Bacteria
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Rates of zinc consumption during cathodic protection of a copper pipeline carrying saline water were measured by the loss in weight technique. The study of sacrificial anode cathodic protection of short copper tube using zinc strip extended axially in the pipe revealed that : (i) The increase of zinc consumption with time of exposure (1-3 h's) at different flow rates (turbulent flow) (300-600 l/hr) while the temperature , solution concentration and the pH were fixed at 20ºC, 3.5%wt NaCl, and pH=8 respectively in absence and presence of bacteria.(ii)Increase of zinc consumption with flow rates (300-600 l/hr) at different temperatures (10-40ºC) while solution concentration and time of exposure were fixed at 3.5 %wt NaCl and 3hr's respect

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Publication Date
Tue Jun 01 2021
Journal Name
Caspian Journal Of Environmental Sciences
Numerical response of predator chrysoperla mutata maclachlan to varying densities of lipaphis erysimi (Kalt.)
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Publication Date
Mon Sep 30 2024
Journal Name
Joiv : International Journal On Informatics Visualization
Evaluation of the Performance of Kernel Non-parametric Regression and Ordinary Least Squares Regression
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Researchers need to understand the differences between parametric and nonparametric regression models and how they work with available information about the relationship between response and explanatory variables and the distribution of random errors. This paper proposes a new nonparametric regression function for the kernel and employs it with the Nadaraya-Watson kernel estimator method and the Gaussian kernel function. The proposed kernel function (AMS) is then compared to the Gaussian kernel and the traditional parametric method, the ordinary least squares method (OLS). The objective of this study is to examine the effectiveness of nonparametric regression and identify the best-performing model when employing the Nadaraya-Watson

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Publication Date
Sun Jun 01 2008
Journal Name
Baghdad Science Journal
Study of Spectral and thermal properties of Selenium Diatomic Halides by Semi-empirical Treatment
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The spectroscopic properties, potential energy curve, dipole moments, total charge density, Electrostatic potential as well as the thermodynamic properties of selenium diatomic halides have been studied using code Mopac.7.21 and hyperchem, semi-empirical molecular orbital of MNDO-method (modified neglected of differential overlap) of parameterization PM3 involving quantum mechanical semi-empirical Hamiltonian. The relevant molecular parameters like interatomic distance, bond angle, dihedral angle and net charge were also calculated.

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Publication Date
Sat Oct 01 2022
Journal Name
Baghdad Science Journal
Determination of Optimal Time-Average Wind Speed Data in the Southern Part of Malaysia
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Mersing is one of the places that have the potential for wind power development in Malaysia. Researchers often suggest it as an ideal place for generating electricity from wind power. However, before a location is chosen, several factors need to be considered. By analyzing the location ahead of time, resource waste can be avoided and maximum profitability to various parties can be realized. For this study, the focus is to identify the distribution of the wind speed of Mersing and to determine the optimal average of wind speed. This study is critical because the wind speed data for any region has its distribution. It changes daily and by season. Moreover, no determination has been made regarding selecting the average wind speed used for w

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Publication Date
Sun Jan 01 2023
Journal Name
مجلة ميسان للدراسات الأكاديمية
Natural Fibers Reinforcement Of Denture Base Materials: Natural Wool Reinforcement:, A Review Of Literature
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Publication Date
Mon Jun 30 2014
Journal Name
Al-kindy College Medical Journal
The effect of cigarette smoking on the clinical outcome of pulmonary tuberculosis in Iraq
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Background: Tobacco smoking and tuberculosis (TB) are two major public health problems; Associations between smoking and tuberculosis including death from tuberculosis have been reported , A reduction in smoking could be expected to have a significant impact on TB incidence and prevalence .
Objectives: to assess the effect of smoking on tuberculosis.
Methods: This study was conducted from June 2011 to June 2012 in 200 patients, adult ( aged 17 years and more), newly diagnosed patients of pulmonary tuberculosis, at the chest and Respiratory Disease Specialized Center in Baghdad. Demographic data, presenting symptoms, data on smoking, and recurrence of disease were compared. Information on smoking status, tobacco smoking was collecte

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Publication Date
Sun Nov 27 2022
Journal Name
Al–bahith Al–a'alami
Gender stereotyping and its relationship to the level of performance of public relations employees
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This article focuses on the relationship of gender to the effectiveness of both women and men in public relations work. Its aim is to identify the extent to which public relations employees are aware of the concept of gender, and to reveal the role of the institution in determining certain roles for both women and men at work, as well as to find out which employees are most effective in public relations activities within the institution.

The researcher uses public relations employees and officials in Iraqi ministries as a research sample to capture the point of view of both parties on the effectiveness of workers in public relations based on the definition of gender. The sample consists of 396 individuals

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Publication Date
Tue Nov 14 2006
Journal Name
Ibn Al-haitham Journal For Pure And Applied Science
[PDF] من iasj.net Synthesis and Characterization of Some New Transition Metal Complexes of Amino
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الوصف New complexes of Cu (ll), Ni (II)„Co (II), and Zn (ll) with 2-amino-5-p-Flouro Phenyl 1, 3, 4-Thiadiazole have been synthesized. The products were isolated, studied and characterized by physical measurements, ie,(FT-IR)„UV-Vis and the melting points were determined. The new Schiff base (L) has been used to prepare some complexes. The prepared complexes were identified and their structural geometry were suggested

Publication Date
Thu Jan 20 2022
Journal Name
Tikrit Journal Of Agriculture Sciences
Effect of seaweed extract (algean) and (atonik) on vegetative growth and yield of cucumber
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