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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
Wed Jun 07 2023
Journal Name
Journal Of Educational And Psychological Researches
Building a Training Program in the development of the Willpower of the Kindergarten Children
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The research aims to build a training program to develop the willpower in the kindergarten children. In order to achieve the objective of the research, the two researchers have developed a Training Program according to the following steps:

- Determining the general objective of the Training Program.

- Determining the behavioral objectives of the Training Program.

- Determining the content of the Training Program.

- Implementing the content of the Training Program sessions.

- Evaluating the Training Program.

The training program consisted of (15) sessions, each session included a set of parts (title, general objective, methods, time and place to implement the sessions, behavioral goals, tool

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Tue Jun 01 2021
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Iop Conference Series: Earth And Environmental Science
Study of the Biological Diversity of Benthic algae in the Tigris River, Baghdad - Iraq
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Abstract<p>The present work included a study of benthic algae on two substrates: rocks and clay on a section of the Tigris River at the Al-Atifiyah site in the fall of 2018. The result of this study was recorded 89 species belong to 50 genus of benthic algae on both substrates and composed of Bacillariophyceae (59.6%, 61.2%), Chlorophyceae (25.8%, 20.4%) and Cyanophyceae (14.5%, 18.3%) respectively on epilithic and epipelic algae. The present study was recorded the highest total algae cell density (1173.2 cells *10<sup>3</sup>/cm<sup>2</sup>) on epilithic algae while the lowest total algae cell density was recorded on epipelic algae (76.95 cells *10<sup>3</sup>/gm). For measure div</p> ... Show More
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Thu Nov 01 2018
Journal Name
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Assessment of Asthmatic Patients’ Quality Of Life in Jordan Fadel Hazza' Ali al-Mahameed.*
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Abstract A descriptive study was conducted in Al-Bashir teaching hospital in Amman city from 15th May 2004 to 15th August 2004 , in order to "Assess the adult asthmatic patients’ quality of life (QOL). Objective: This study aimed at identifying the domains of (Environmental, Physical, Daily Living Activity, Drug and Medication, Psychological , and Social), Methodology : A Purposive (Non-Probability) sample of (100) adult asthmatic patients visited the emergency department and outpatient clinic of chest department in Al-bashir hospital .A Questionnaire was constructed for the purpose of the study, and compris

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Publication Date
Tue Jan 01 2019
Journal Name
Indian Journal Of Public Health Research &amp; Development
Comparison of the Cyclic Fatigue of Protaper Next, 2Shape and Hyflex EDM Using Glyde
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Effect of adding Biohealth, zeolite and mineral fertilizer on some measurements of potato yield
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To know the effect of bio-enhancer (zeolite), biohealth, mineral fertilizers and their interactions, the possibility of replacing mineral fertilizers with bio-enhancers and bio-enhancers, and their effect on some potato yield measurements. A field experiment was conducted at one of the field stations of the College of Agricultural Engineering Sciences, University of Baghdad, near the electronic calculator center, research station (F) in Al-Jadriya region in the loam mixture soil during autumn season 2021-2022 AD, It was designed using a completely randomized block design (RCBD) with three replicates. The factors of the study experiment included three levels of zeolite (0, 6 tons ha-1, and 12 tons ha-1), which were symbolized by (Z0)

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Publication Date
Tue Dec 13 2011
Journal Name
Iraqi Journal Of Laser
The Efficacy of Er:YAG Laser on Intrapulpal Temperature Rise of Class V Cavity Preparation
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The objective of this study is to determine the efficacy of class V Er:YAG laser (2940 nm) cavity preparation and conventional bur cavity preparation regarding Intrapulpal temperature rise during cavity preparation in extracted human premolar teeth. Twenty non carious premolar teeth extracted for orthodontic purposes were used and class V cavity preparation was applied both buccal and lingual sides for each tooth .Samples were equally grouped into two major groups according to cavity depth (1mm and 2mm). Each major group was further subdivided into two subgroupsof ten teeth for each (twenty cavities for each subgroup). TwinlightEr:YAG laser (2940 nm) with 500mJ pulse energy, P.R.R of 10 Hz and 63.69 J/cm2 energy density was used. The ana

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Publication Date
Sun Mar 01 2009
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The Optimum Conditions for Production of Soya Peptone by Acidic Hydrolysis of Soya Proteins
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     This study was carried out to obtain the optimum conditions necessary for the process of soya protein hydrolysis by using hydrochloric acid (as a chemical catalyst) instead of the papain enzyme (as a biological catalyst), for the production of soya peptone. These conditions are implemented to test the effect of the variables of the process of hydrolysis on the nature and quality of the product.

        The production of soya peptone was studied for their importance in the process of preparing and producing the culture media used in medical and microbiological laboratories.

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Publication Date
Wed Aug 28 2019
Journal Name
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Influence of Liquid Asphalt on Resilient Modules and Permanent Deformation of Recycled Asphalt Concrete
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Tests were performed on Marshall samples and were implemented for permanent deformation and resilient modulus (Mr) under indirect tensile repeated loading (ITRL), with constant stress level. Two types of liquid asphalt (cutback and emulsion) were tried as recycling agents, aged materials that were reclaimed from field (100% RAP), samples were prepared from the aged mixture, and two types of liquid asphalt (cutback and emulsion) with a weight content of 0.5% were utilized to prepare a recycled mixture. A group of twelve samples was prepared for each mixture; six samples were tested directly for ITRL test (three samples at 25˚C and three samples at 40˚C), an average value for ITRL for every three samples was calculated (

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Publication Date
Mon Dec 26 2022
Journal Name
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The directorial vision of the theatrical text In the concept of a picture theater
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Sun Mar 01 2020
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Intended for getting good estimates with more accurate results, we must choose the appropriate method of estimation. Most of the equations in classical methods are linear equations and finding analytical solutions to such equations is very difficult. Some estimators are inefficient because of problems in solving these equations. In this paper, we will estimate the survival function of censored data by using one of the most important artificial intelligence algorithms that is called the genetic algorithm to get optimal estimates for parameters Weibull distribution with two parameters. This leads to optimal estimates of the survival function. The genetic algorithm is employed in the method of moment, the least squares method and the weighted

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