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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 Apr 04 2017
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
INVESTIGATION OF BACTERIAL CONTAMINANTS IN FREEZERS KEEPING FROZEN FOOD IN LOCAL MARKETS: INVESTIGATION OF BACTERIAL CONTAMINANTS IN FREEZERS KEEPING FROZEN FOOD IN LOCAL MARKETS
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This study aimed to evaluate the occurrence of microbial contamination in food keeping freezers in some local markets in Baghdad city/ Iraq, as well as the contamination of the hands of workers in markets, and the possibility of contamination caused by the transport of food. 30 samples of snow ice found in food keeping freezers in local markets was randomly collected, and 30 swabs from workers hands were taken from the same markets at the same time. Microbiological examination of ice samples was conducted as well as the hands of workers’swabs, and the bacteria were isolated and diagnosed through microbiological and biochemical tests followed. Microbial test results showed some isolates of bacteria in ice samples obtained from food keep

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Publication Date
Mon Apr 17 2017
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
INVESTIGATION THE CONTENT OF SOME HEAVY METALS IN COLORED PLASTIC TABLE DISHES.: INVESTIGATION THE CONTENT OF SOME HEAVY METALS IN COLORED PLASTIC TABLE DISHES.
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The aim of this study is to investigate the existence of some heavy metals (lead, cadmium, chromium) in colored plastic table dishes and study the migration of these metals to the food meals and the affecting factors in migration , such as storage period and food temperature. Six kinds of colored plastic table dishes were collected from Baghdad markets. The heavy metals in table dishes and in the prepared food meals put in them were estimated using atomic absorption spectrophotometer (Shimadzu A5000). The results indicated the existence of lead in all samples (1.61_1.00 mg/ kg) and chromium in three samples (0.85_0.97 mg/ kg) while other samples are free of chromium, and cadmium. Investigating the migration of these metals to food at dif

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Publication Date
Wed Jun 14 2023
Journal Name
Al-academy
Functional enhancement and its reflection on industrial product systems
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The research tagged (functional enhancement and its reflection on industrial product systems) focused on the possibility of enhancing industrial products in terms of form and functionality in a way that they are able to meet the needs of the user through the impact of technology and modern technologies on the functional enhancement of industrial products and their effectiveness in achieving formal and functional design variables, and producing products Industrial products are highly efficient and durable in order to improve them in order to meet the needs of the user, the transfer of technology between life forms and industrial products is desirable because the functional enhancement processes that occurred in general on industrial produ

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Publication Date
Mon Jan 09 2023
Journal Name
2023 15th International Conference On Developments In Esystems Engineering (dese)
Deep Learning-Based Speech Enhancement Algorithm Using Charlier Transform
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Publication Date
Wed Dec 22 2021
Journal Name
Antibiotics
Classic vs. Novel Antibacterial Approaches for Eradicating Dental Biofilm as Adjunct to Periodontal Debridement: An Evidence-Based Overview
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Periodontitis is a multifactorial chronic inflammatory disease that affects tooth-supporting soft/hard tissues of the dentition. The dental plaque biofilm is considered as a primary etiological factor in susceptible patients; however, other factors contribute to progression, such as diabetes and smoking. Current management utilizes mechanical biofilm removal as the gold standard of treatment. Antibacterial agents might be indicated in certain conditions as an adjunct to this mechanical approach. However, in view of the growing concern about bacterial resistance, alternative approaches have been investigated. Currently, a range of antimicrobial agents and protocols have been used in clinical management, but these remain largely non-v

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Publication Date
Thu Oct 31 2013
Journal Name
Al-khwarizmi Engineering Journal
Enhancement of a Power System Transient Stability Using Static Synchronous Series Compensator SSSC
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Static Synchronous Series Compensator (SSSC) is a well known device for effectively regulating the active power flow in a power system. In this paper, the SSSC linearized power flow equations are incorporated into Newton-Raphson algorithm in a MATLAB written program to investigate the control of active poweer flow and the transient stability of a five bus and a thirty bus IEEE test systems, during abnormal conduction (three phase fault near buses). A comparison of the results obtained for the base case without SSSC and with it to investigate the effectiveness of the device on both of the active power flow and the transient stability.

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Publication Date
Tue Dec 31 2013
Journal Name
Al-khwarizmi Engineering Journal
Enhancement of Iraqi Light Naphtha Octane Number Using Pt Supported HMOR Zeolite Catalyst
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The hydroconversion of Iraqi light straight run naphtha was studied on zeolite catalyst. 0.3wt.%Pt/HMOR catalyst was prepared locally and used in the present work. The hydroconversion performed on a continuous fixed-bed laboratory reaction unit. Experiments were performed in the temperature range of 200 to 350°C, pressure range of 3 to 15 bars, LHSV range of 0.5-2.5h-1, and the hydrogen to naphtha ratio of 300.

The results show that the hydroconversion of Iraqi light straight naphtha increases with increase in reaction temperature and decreases with increase in LHSV.

High octane number isomers were formed at low temperature of 240°C. The selectivity of hydroisomerization improved by increasing reaction pressu

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Publication Date
Tue Dec 01 2020
Journal Name
Iraqi Journal Of Physics
Enhancement of thermal stability and wettability for epoxy/Cu coated carbon fiber composites
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    This research study the effect of surface modification and copper (Cu) plating carbon fiber (CF) surface on the thermal stability and wettability of carbon fiber (CF)/epoxy (EP) composites. The TGA result indicates that the thermal-stability of carbon fiber may be enhanced after Cu coating CF. TGA curve showed that the treatment temperature was enhanced thermal stability of Ep/CF, this is due to the oxidation during heating. The Cu plating increased the thermal conductivity, this increase might be due to reduce in contact resistance at the interface due to chemical modification and copper plating and tunneling resistance.

   The increase of surface polarity after coating cause decreas

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Publication Date
Fri Mar 01 2019
Journal Name
Al-khwarizmi Engineering Journal
The Effect of Micro and Nano Material on Critical Heat Flux (CHF) Enhancement
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The Nano materials play a very important role in the heat transfer enhancement. An experimental investigation has been done to understand the behaviors of nano and micro materials on critical heat flux. Pool boiling experiments have used for several concentrations of nano and micro particles on a 0.4 mm diameter nickel chrome (Ni-Cr) wire heater which is heated electrically at atmospheric pressure. Zinc oxide(ZnO) and silica(SiO2) were used as a nano and micro fluids with concentrations (0.01,0.05,0.1,0.3,0.5,1 g/L), a marked enhancement in CHF have been shown in the results for nano and micro fluids for different concentrations compared to distilled water. The deposition of the nano particles on the heater surface was the rea

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Publication Date
Sun Nov 01 2015
Journal Name
Journal Of Engineering
Enhancement Solution to Improve Remediation of Soil Contaminated with Lead by Electrical Field
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A laboratory investigation of six different tests were conducted on silty clay soil spiked with lead in concentrations of 1500 mg/kg. A constant DC voltage gradient of 1 V/cm was applied for all these tests with duration of 7 days remediation process for each test. Different purging solutions and addition configurations, i.e. injection wells, were investigated experimentally to enhance the removal of lead from Iraqi soil during electro-kinetic remediation process. The experimental results showed that the overall removal efficiency of lead for tests conducted with distilled water, 0.1 M acetic acid, 0.2 M EDTA and 1 M  ammonium citrate as the purging solutions were equal to 18 %, 37 %, 42 %, and 29 %, respectively. H

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