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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 Feb 01 2015
Journal Name
Journal Of Economics And Administrative Sciences
The possibility of applying CAPP technology to improve the quality of the product
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     The research deals with A very important two subjects, computer aided process planning (CAPP) and Quality of product with its dimintions which identified by the producer organization, the goal of the research is to Highlight and know the role of the CAPP technology to improve quality of the product of (rotor) in the engines factory in the general company for electrical industries, The research depends case study style by the direct visits of researcher to the work location to apply the operational paths generated by specialized computer program designed by researcher, and research divides into four axes, the first regard to the general structure of the research, the second to the theoretical review, the t

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Publication Date
Fri Mar 01 2019
Journal Name
Al-khwarizmi Engineering Journal
Study the Effect of Hydrolysis Variables on the Production of Soya Proteins Hydrolysis
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This study was conducted to determine the effects of concentration of hydrochloric acids, temperature, and time on the hydrolysis of soya proteins (defatted soya flour) by determining the value of total protein nitrogen  concentration, and amino nitrogen concentration of protein, peptides, and amino acids, and then calculated the hydrolysis rate of proteins.

        The variables of the conditions of hydrolysis process was achieved in this study with the following range value of tests parameter:

  • Concentration of HCl solution ranged between 1-7 N,
  • Hydrolysis temperature ranged between 35-95 °C, and
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Publication Date
Tue Oct 30 2018
Journal Name
Iraqi Journal Of Physics
Influence of substrates on the properties of cerium -doped CdO nanocrystalline thin films
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Transparent thin films of CdO:Ce has been deposited on to glass and silicon substrates by spray pyrolysis technique for various concentrations of cerium (2, 4, and 6 Vol.%). CdO:Ce films were characterized using different techniques such as X-ray diffraction (XRD), atomic force microscopy(AFM) and optical properties. XRD analysis show that CdO films exhibit cubic crystal structure with (1 1 1) preferred orientation and the intensity of the peak increases with increasing's of Ce contain when deposited films on glass substrate, while for silicon substrate, the intensity of peaks decreases, the results reveal that the grain size of the prepared thin film is approximately (73.75-109.88) nm various with increased of cerium content. With a sur

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Publication Date
Wed Aug 30 2023
Journal Name
Al-kindy College Medical Journal
Factors associated with Exacerbation of Myasthenia Gravis in a Group of Iraqi Patients
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Background: Myasthenia gravis is an autoimmune disease of the neuromuscular junction that results in fluctuating muscle weakness as well as significant fatigue. Disease exacerbation is a critical condition, and the predisposing factors for it need to be identified to improve preventive measures.

Objectives:  Our study aims to determine the predisposing factors for myasthenia gravis exacerbations in a group of Iraqi patients.

Subjects and Methods: A total number of 30 myasthenia gravis patients were admitted to the hospital with an exacerbation of their symptoms, determined as the development of functional disability, dysphagia, or respiratory fai

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Wed Apr 01 2020
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Civil Engineering Journal
Model Development for the Prediction of the Resilient Modulus of Warm Mix Asphalt
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Increasing material prices coupled with the emission of hazardous gases through the production and construction of Hot Mix Asphalt (HMA) has driven a strong movement toward the adoption of sustainable construction technology. Warm Mix Asphalt (WMA) is considered relatively a new technology, which enables the production and compaction of asphalt concrete mixtures at temperatures 15-40 °C lower than that of traditional hot mix asphalt. The Resilient modulus (Mr) which can be defined as the ratio of axial pulsating stress to the corresponding recoverable strain, is used to evaluate the relative quality of materials as well as to generate input for pavement design or pavement evaluation and analysis. Based on the aforementioned preface, it is

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Publication Date
Wed Feb 20 2019
Journal Name
Iraqi Journal Of Physics
Preparation of polyaniline polymer and using it as a Vapor sensor of acids
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 Polyaniline organic Semiconductor polymer was prepared by oxidation polymerization by adding hydrochloric acid concentration of 0.1M and potassium per sulfate concentration of 0.2M to 0.1M of aniline at room temperature, the polymer was deposited at glass substrate, the structural and optical properties were studies through UV-VIS, IR, XRD measurements, films have been operated as a sensor of vapor  H2SO4 and HCl  acids.

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Publication Date
Mon Jun 12 2006
Journal Name
Iraqi Journal Of Laser
Effect of Preheating on the Parameters of Laser Keyhole Welding Process: Analytical Study
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In this work, results of a mathematical analysis of the role of workpiece preheating in laser keyhole welding were presented. This analysis considered the steady-state welding as well as certain range of boundary conditions over which preheating effect would be indicated. This work is an attempt to interpret the role of preheating to increase welding depth and perform keyhole welding with high quality using physical and thermal properties of steel alloys.

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Publication Date
Wed Apr 01 2015
Journal Name
Journal Of Economics And Administrative Sciences
Classification & Evaluation of Evidence of deprivation in Iraq (2009) by using Cluster analysis
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       The study aimed to reach the best rating for the views and variables in the totals characterized by qualities and characteristics common within each group and distinguish them from aggregates other for the purpose of distinguishing between Iraqi provinces which suffer from deprivation, for the purpose of identifying the status of those provinces in the early allowing interested parties and regulators to intervene to take appropriate corrective action in a timely manner. Style has been used cluster analysis Cluster analysis to reach the best rating to those totals from the provinces that suffer from problems, where the provinces were classified, based on the variables (Edu

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Publication Date
Mon Mar 30 2020
Journal Name
Plant Archives
Survey of the insect pests from some orchards in the middle of Iraq
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Publication Date
Sun Jun 12 2011
Journal Name
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The Effect of Chlorine Concentration on the Optical Constants of SnS Thin Films
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Chlorine doped SnS have been prepared utilizing chemical spray pyrolysis. The effects of chlorine concentration on the optical constants were studied. It was seen that the transmittance decreased with doping, while reflectance, refractive index, extinction coefficient, real and imaginary parts of dielectric constant were increased as the doping percentage increased. The results show also that the skin depth decrease as the chlorine percentage increased which could be assure that it is transmittance related.

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