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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
Sun Aug 25 2019
Journal Name
Journal Of University Of Babylon For Engineering Sciences
Observation of Consolidation and Permeability Parameters of Soil Stabilized By Cutback Asphalt
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For design purposes, it`s necessary to know the compression rate of soil layers which might be happened when it`s subjected to effective stresses. Also, it`s essential to know the rate of flow through soil mass specially for the design of marine structures or earth embankment. These two important behavior could be predicted from the coefficient of consolidation (Cv) and the coefficient of permeability (k). This study shows the effect of cutback asphalt stabilization on Cv and k and other compressibility factors, the investigation was done for silty clay samples, specimens were prepared by mixing the soil with different percentage of asphalt from (0-10)% and subjected to one-dimensional consolidation test of 50mm diameter and 20mm height wer

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Publication Date
Mon Jun 01 2009
Journal Name
Al-khwarizmi Engineering Journal
Automatic Optimization System of Cutting Condition for Different Types of Machining Processes
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This research aims at calculating the optimum cutting condition for various types of machining methods, assisted by computers, (the computer program in this research is designed to solve linear programs; the program is written in v. basic language). The program obtains the results automatically, this occur through entering the preliminary information about the work piece and the operating condition, the program makes the calculation actually by solving a group of experimental relations, depending on the type of machining method (turning, milling, drilling). The program was transferred to package and group of windows to facilitate the use; it will automatically print the initial input and optimal solution, and thus reduce the effort and t

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Publication Date
Thu Apr 13 2017
Journal Name
Journal Of Multidisciplinary Engineering Science Studies (jmess)
The Effect Of Thickness On Some Physical Properties Of CdSe Thin Films
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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
The Effect of Preservation on the Shelf Life of Laboratory Processed Biscuit
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This study has been conducted to investigate the influence of preservatives(sodium propionate and potassium sorbate) at different levels to extend the storage life of laboratory processed biscuit.The results have shown that When%0.10 sodium propionate was added bacteria and fungi was not found for three months while found in the fourth month of storage.However bacteria and mold didnot grow until the sixth month of storage as %0.20 and %0.30 concentration was used. On the other side as %0.03 potassium sorbate was used,the growth of bacteria was cheched for 3 months and 4 months for molds..When %0.06 potassium sorbate was used no growth of bacterial or mold was found until the sixth month of storage . Three types of bacteria have been appeare

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Publication Date
Sat Sep 30 2023
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The reflection of environmental quality costs on the evaluation of environmental performance
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Abstract:

               The research aims to achieve defining the concept of environmental quality and associated costs. Studying the impact of environmental quality costs on the performance of economic units. Measuring the relationship between environmental quality and environmental performance of the units. Where the research problem is represented in the weak awareness of some economic units of the importance of environmental quality costs and their impact on evaluating environmental performance, and this leads to neglecting environmental considerations and not improving environmental performance effectively, which negatively affects the en

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Publication Date
Sun Dec 06 2015
Journal Name
Baghdad Science Journal
Study the genesis of the Moons of Jupiter and their Physical Properties
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A developed model has been put for the hypothesis of capturing moons in explaining the origin of Jupiter moons, and study the change of the orbital properties of these satellites as well as the distance from the planet. Jupiter moons were divided into two types according to their physical and orbital properties, they are the moons , which are formed from the same material as the planet, so it was named the original moons ,while the moons that have been captured from the surrounding space was renamed exotic moons . And the moons of exotic origin asteroid belt and the Kuiper belt in the region which is behind Neptune, the origin of each clique of moons is an asteroid fragmented after colliding previously with another body and

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Gender differences in achievements among students of the Iraqi college of medicine
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This study was conducted to test the hypothesis that the duration of time spent by the student inside the examination rooms answering the all kinds of written ex-amination questions has some kind of a positive effect on the final score he will get from that exam. And if there arc gender differences in this respect. Students and methods: Data on the final examinations of the autumn quarter was gathered on 892 examina-tions conducted at the end of this quarter , this included male participants of 566 and females of 326. Examinations were on twenty different subjects , including all of the first five years of the undergraduate students of Iraqi College of Medicine for the academic year 2002 — 2003 . The scheduled time of the examinations was

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Publication Date
Sat Aug 01 2015
Journal Name
Journal Of Engineering
Influence of Internal Sulfate Attack on Some Properties of High Strength Concrete
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One of the most important problems that faces the concrete industry in Iraq is the deterioration due to internal sulfate attack , since it reduces the compressive strength and increases the expansion of concrete. Consequently, the concrete structure may be damage .The effects of total and total effective sulfate contents on high strength concrete (HSC) have been studied in the present study. The research studied the effect of sulfate content in cement , sand and gravel , as well as comparing the total sulfate content with the total effective SO3 content. Materials used were divided into two groups of SO3 in cement ,three groups of SO3 in sand ,and two groups of SO3 in gravel. The results show that considering the total effective sulfate con

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Effect of Adding (Binder-Plastisizer-Lubricat) on the Physical Properties of Kaolin
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The study concern with the preparation of three type of mixtures; which are prepared from different percentage of polyvenil Butyral, Di-n-butyl phathalate and paraffin wax pastillated. The solvent used is Xylolzul analyses. After washing, Drying and milling the kaolin Dukhla, as a matrix in this study, and by using sieving Tech. The range of particle size used is less than and less than as a mesh batch. The added percentage from prepared mixture were 5% and 10% to 95% and 90% of the matrix respectively. Then disk samples were prepared by using a compaction pressure with heating. After cooling and drying the samples were undergo heat treatment in the range of (1250 – 1350) oC. The measurement of shrinkage and Dielectric properties sho

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Publication Date
Fri Mar 31 2017
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
The Influence of Eggshell Particle Sizes on the Adsorption of Organic Dye
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This work aimed to use effective, low-cost, available, and natural adsorbents like eggshells for removal of  hazardous organic dye result from widely number of  industries and study the influence of different eggshell particle size (75, 150) Mm.  The adsorbent was characterized by SEM, EDX, BET and FTIR . The initial pH of dye solutions  varying from 4 to 10 , the initial concentrations of methyl violet (MV) 2B range (20-80) mg/L, dosage range (0.5-10) g, contact time (30-180) min, and particles size of the adsorbent (75, 150) Mm were selected to be studied. Two adsorption isotherms models have been used to fit the experimental data. Langmuir and Freunlich models were found to more represent the experiments with high

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