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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 Jun 15 2021
Journal Name
Al-academy
The semiotic of the Islamic blazon - a related analytical study between the Islamic blazon and its publicity message: رغده بنت فيصل بن خضر الدعواني
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This study discusses the semiotic of the Islamic blazon - a related analytical study between the Islamic blazon and its visual publicity message. The aim of the current study is to explore the related relationship between the Islamic blazon and its visual publicity message. The sample is contained Five of Islamic blazon in the Mamelukes period which is between 1250 to 1517. The methodology is descriptive-analytical, and the result is that there is a clear relation between the Islamic blazon with its visual publicity message. This study's recommendation is to go towards analyzing the meanings of the cultural legacies of the Islamic civilization, and researching the implicit meanings accompanying these features leads to a deeper understand

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Publication Date
Mon Dec 20 2021
Journal Name
Baghdad Science Journal
Synthesizing, Structuring, and Characterizing Bioactivities of .Cr(III), La(III), and Ce(III) .Complexes with Nitrogen, Oxygen .and Sulpher donor bidentate Schiff base ligands
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Two Schiff bases, namely, 3-(benzylidene amino) -2-thioxo-6-methyl 2,5-dihydropyrimidine-4(3H)-one (LS])and 3-(benzylidene amino)-6-methyl pyrimidine 4(3H, 5H)-dione(LA)as chelating ligands), were used to prepare some complexes of Cr(III), La(III), and Ce(III)] ions. Standard physico-chemical procedures including metal analysis M%, element microanalysis (C.H.N.S) , magnetic susceptibility, conductometric measurements, FT-IR and UV-visible Spectra were used to identify Metal (III) complexes and  Schiff bases (LS) and (LA). According to findings, a [Cr(III) complex] showed six coordinated octahedral geometry, while [La(III), and Ce(III) complexes]were structured with coordination number seven.  Schiff's bases a

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Publication Date
Sat Oct 08 2022
Journal Name
Journal Of Computational Design And Engineering
Twisted-fin parametric study to enhance the solidification performance of phase-change material in a shell-and-tube latent heat thermal energy storage system
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Abstract<p>Phase change material (PCM) is considered as one of the most effective thermal energy storage (TES) systems to balance energy supply and demand. A key challenge in designing efficient PCM-based TES systems lies in the enhancement of heat transmission during phase transition. This study numerically examines the privilege of employing twisted-fin arrays inside a shell-and-tube latent heat storage unit to improve the solidification performance. The presence of twisted fins contributes to the dominating role of heat conduction by their curved shapes, which restricts the role of natural convection but largely aids the overall heat-transfer process during solidification. The heat-discharge </p> ... Show More
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Publication Date
Mon Nov 01 2021
Journal Name
Journal Of Engineering
Performance Evaluation of Pole Placement and Linear Quadratic Regulator Strategies Designed for Mass-Spring-Damper System Based on Simulated Annealing and Ant Colony Optimization
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This paper investigates the performance evaluation of two state feedback controllers, Pole Placement (PP) and Linear Quadratic Regulator (LQR). The two controllers are designed for a Mass-Spring-Damper (MSD) system found in numerous applications to stabilize the MSD system performance and minimize the position tracking error of the system output. The state space model of the MSD system is first developed. Then, two meta-heuristic optimizations, Simulated Annealing (SA) optimization and Ant Colony (AC) optimization are utilized to optimize feedback gains matrix K of the PP and the weighting matrices Q and R of the LQR to make the MSD system reach stabilization and reduce the oscillation of the response. The Matlab softwar

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Publication Date
Sat Jan 01 2022
Journal Name
Journal Of The Mechanical Behavior Of Materials
The slenderness ratio effect on the response of closed-end pipe piles in liquefied and non-liquefied soil layers under coupled static-seismic loading
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Abstract<p>This study presents the findings of a 3D finite element modeling on the performance of a single pile under various slenderness ratios (25, 50, 75, 100). These percentages were assigned to cover the most commonly configuration used in such kind of piles. The effect of the soil condition (dry and saturated) on the pile response was also investigated. The pile was modeled as a linear elastic, the surrounded dry soil layers were simulated by adopting a modified Mohr-Coulomb model, and the saturated soil layers were simulated by the modified UBCSAND model. The soil-pile interaction was represented by interface elements with a reduction factor (R) of 0.6 in the loose sand layer and 0.7 in t</p> ... Show More
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Publication Date
Tue Jan 23 2018
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
ESTIMATION OF SOME CHEMICAL AND PHYSICAL PROPERTIES USING A WATER TREATMENT UNIT VORTISAND COMPARED TO THEIR CONCENTRATION IN WATER PRODUCED BY TRIDINTINAL DRINKING WATER PROJECTS IN BAGHDAD.: ESTIMATION OF SOME CHEMICAL AND PHYSICAL PROPERTIES USING A WATER TREATMENT UNIT VORTISAND COMPARED TO THEIR CONCENTRATION IN WATER PRODUCED BY TRIDINTINAL DRINKING WATER PROJECTS IN BAGHDAD.
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This study was conducted to determine the ability of water treatment system (Vortisand) to reduce some chemical and physical properties for tigris river raw water, It consisted of turbidity, electrical conductivity, pH, total hardness, calcium Hardness as well as temperature in order to determine the unit`s efficiency for reducing their concentration as compared to those in the water produced by some classical potable water projects (Dora and Wathba) in Baghdad. Samples were collected during the cold months (December 2016 and January 2017) and during the hot months (May and June 2017). The results showed that this system has the ability to reduce some properties such as turbidity, the values were 215NTU in raw water and decreased to NTU

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Publication Date
Mon Dec 20 2021
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
STUDY THE PHYSICAL AND CHEMICAL PROPERTIES AND DETERMINATION THE CYTOTOXICITY OF KOJIC ACID PRODUCED FROM THE LOCAL ISOLATE ASPERGILLUS FLAVUS WJF81 AND THEIR EFFECTS ON CONSUMER HEALTH.: STUDY THE PHYSICAL AND CHEMICAL PROPERTIES AND DETERMINATION THE CYTOTOXICITY OF KOJIC ACID PRODUCED FROM THE LOCAL ISOLATE ASPERGILLUS FLAVUS WJF81 AND THEIR EFFECTS ON CONSUMER HEALTH.
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Steps were taken to obtain the Kojic acid crystals from local fungal isolation A. flavus WJF81 by separating the fermentation products from the fungus mycelium from the production plant at the centrifuge at a speed of 5000 cycles for 10 minutes. The extraction was followed by ethyl acetate then supernatant concentrate by using rotary evaporator, and dried with heat oven 37ºC. Long, yellowish, pristine acid crystals were obtained that examined the optical microscope with a magnification force of 10x and 40x. The melting point of kojic acid was determined between 152.9-153.5 °C Results of the diagnosis of Kojic acid by applying High pressure liquid chromatography HPLC technique showed that the acid was at one peak, which was close to the

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Publication Date
Thu Dec 31 2020
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
ASTUDYON THERECORDOF EVALUATINGTHE SUPPLIERSACCORDING TO THE CONCEPT OF QUALITY AND BENEFITING FROM IT IN PRACTICE IN AL-FURAT STATE COMPANY AND FINDING POSSIBLE PROPOSALS FOR ITS DEVELOPMENT: ASTUDYON THERECORDOF EVALUATINGTHE SUPPLIERSACCORDING TO THE CONCEPT OF QUALITY AND BENEFITING FROM IT IN PRACTICE IN AL-FURAT STATE COMPANY AND FINDING POSSIBLE PROPOSALS FOR ITS DEVELOPMENT
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Success in selecting the best among the sources of supply is one of the most important factors in the efficiency of the procurement activity in the company, because the proper selection of the source of the supply significantly affect the achievement of what is desired by the factors of quality, quantity, price and service, and the ability of the competent supplier to meet everything associated with this Factors of commitments, hereby supporting the procurement function's efforts to fully discharge its responsibilities, and in view of adopting of Al-Furat company quality management system by applying the standards of ISO (9001: 2015) and purpose of getting the on-demand benefits from the application of international standards reg

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Publication Date
Tue Jan 01 2013
Journal Name
Bio-genetics Journal
Measuring the toxicity of Heat Stable Enterotoxin (a) produced by Enterotoxigenic Escherichia coli on human blood lymphocyte from normal and colorectal cancer patients in vitro
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This research was conducted to measure the safety of heat stable enterotoxin a (STa) produced by enterotoxigenic Escherichia coli, through studying its toxic effect on human blood lymphocyte, since it showed a promising effect in reducing the proliferation of colorectal cancer cells. the cytogenetic effects of (STa) by using five different concentrations (100, 200, 400, 800 and 1600μg/ml) in comparison with negative (PBS, Phosphate buffer saline) and positive (MMC, Mitomycin C) at concentration of 5μg/ml, controls on human blood lymphocytes obtained from both (10) normal healthy persons and (20) colorectal cancer patients was measured by employing the following parameters: mitotic index, blast index, chromosomal aberrations and micronucle

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Mon Feb 01 2021
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Meta Gene
Association analysis of FTO gene polymorphisms rs9939609 and obesity risk among the adults: A systematic review and meta-analysis” Meta Gene (2020) 7–7/100832
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Background: Obesity typically results from a variety of causes and factors which contribute, genetics included, and style of living choices, and described as excessive body fat accumulation of body fat lead to excessive body, is a chronic disorder that combines pathogenic environmental and genetic factors. So, the current study objective was to investigate the of the FTO gene rs9939609 polymorphism and the obesity risk. Explaining the relationship between fat mass and obesity-associated gene (FTO) rs9939609 polymorphism and obesity in adults. Methods: Identify research exploring the association between the obesity risk and the variation polymorphisms of FTO gene rs9939609. We combined the modified odds ratios (OR) as total groups and subgro

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