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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 Dec 01 2020
Journal Name
Journal Of Engineering Science And Technology
Quantitative and qualitative assessment of groundwater: The case of Khanaqin alluvial (Iraq
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Publication Date
Mon Jan 01 2018
Journal Name
World Journal Of Dentistry
Factors affecting the Duration of Surgical Extraction of Impacted Mandibular Third Molars
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Aim The aim of this study is to evaluate the effect of demographic, clinical, and radiographic factors on the duration of surgical extraction of impacted lower third molars. Materials and methods This retrospective study included patients who underwent surgical removal of impacted lower third molars, and the investigated factors were demographic data including age and gender, radiographic data including the impacted tooth angulation and depth of impaction and ramus relation, and clinical data including the state of eruption of the impacted teeth. These factors were evaluated for association with the duration of surgery. Descriptive statistical analysis included percentages and mean ± standard deviation (SD). Student's t-test was used to co

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Publication Date
Tue Dec 06 2022
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of Nurses' Attitudes towards Patients’ End of life in Diyala Governorate
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Abstract:

Objectives: To assess nurses' attitude toward end of life phase. To find out  relationships between nurses attitude and socio demographic data (age, gender, level of education, years of experience).

Methodology: A descriptive cross-sectional study design is carried out to assess the attitude on nurses concerning patient at the end of life phase at critical care units, from the period of (1nd November 2021) to (1th February 2022). A probability sample random sampling technique used. Then, the number of participants in Baquba Teaching Hospital and general al khalis hospital were determined by using rando

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Publication Date
Mon Oct 02 2023
Journal Name
Journal Of Engineering
Numerical Analysis of the Stability of Bridge Foundation Pile under Earthquakes Effect
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This study was chosen because of the entry of our regions into the seismic zone recently, where Diyala governorate was hit by the Halabja earthquake in 2017 by 7.3Mw. Therefore, the impact of earthquakes will be studied on the AL-Mafraq bridge foundations piles located in Iraq- east of Baghdad in Diyala Governorate and the extent of its resistance to the Halabjah, EL-Centro, and Kobe earthquakes with acceleration 0.1g, 0.34g, and 0.58g respectively. After modeling and performing the analysis by using Midas Gts-Nx software, the settlement (mm) results at nine nodes (four nodes for the pile cap and five nodes for the piles) were obtained for each of Halabjah, EL-Centro, and Kobe earthquakes to know the resistance of the br

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Publication Date
Sun Nov 01 2015
Journal Name
Journal Of Engineering
Experimental Evaluation of Thermal Performance of Solar Assisted Vapor Compression Heat Pump
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The thermal performance of indirect expansion solar assisted heat pump, IX-SAHP, was investigated experimentally under Iraqi climate. An Indirect-Solar Assisted Heat Pump system was designed, built, instrumented and tested. Experimental tests were conducted by varying the controlling parameters to investigate their effects on the thermal performance of the IX-SAHP such as cooling water flow rate, heating water flow rate, ambient temperature and solar radiation intensity. The investigation covered values of cooling water flow rate of (2, 3, 4, 5 l/min) and heating water flow rate of (2, 3, 4, 5 l/min) under meteorological condition of Baghdad from November 2014 to January 2015.

The results indicated that the performance of the IX-

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Publication Date
Fri Dec 30 2011
Journal Name
Al-kindy College Medical Journal
The Role of Some Medicinal Plants in the Management of Peptic Ulcer
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Background: Plants used in folk medicine for
the treatment of peptic ulcer diseases is a very
promising approach to overcome the limitations of
classical medicines.
Aim: To explore the efficacy of medicinal
plants, namely turmeric, garlic and marshmallow,
in eradication of H. pylori.
Methods: This prospective study was carried out
on 225 of well-known dyspeptic patients who were
divided into four groups; a control group (received
classical medical therapy) and three other groups
that received one of the three medicinal plants,
plus the same therapy used in the control group.
The follow up was done by using a questionnaire
form, endoscopic examination, and determination
of serum levels of anti

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Publication Date
Wed Apr 01 2020
Journal Name
Journal Of Economics And Administrative Sciences
The Impact of Plagiarism on the Quality of Scientific Researches “Empirical Study”
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The purpose of this research is to study the quality of scientific research at the University of Baghdad in light of scientific piracy and plagiarism of research and results and attribute it to others intentionally or unintentionally. Proactive writing such as stealing ideas or synthesizing the results of one another over others and its negative impact on the quality of scientific outputs and the reputation of educational organizations through an exploratory study in the faculties of the University of Baghdad, scientific and humanitarian. As for the aims of the study, it was determined by determining the negative impact of piracy on scientific research. A Likert five-point scale was used in this research. The research community c

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Publication Date
Tue Dec 30 2008
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Effect of operation conditions on Catalytic Oxidation of Phenol in Aqueous Solution
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This work was conducted to study the oxidation of phenol in aqueous solution using copper based catalyst with zinc as promoter and different carrier, i.e. γ-Alumina and silica. These catalysts were prepared by impregnation method.
The effect of catalyst composition, pH (5.6-9), phenol to catalyst concentration ratio (2-0.5), air feed rate (30-50) ml/s, stirring speed (400-800) rpm, and temperature (80-100) °C were examined in order to find the best conditions for phenol conversion.
The best operating conditions which lead to maximum phenol conversion (73.1%) are : 7.5 pH, 4/6 phenol to catalyst concentration, 40 ml/s air feed rate, 600 rpm stirring speed, and 100 °C reaction temperature. The reaction involved an induction period

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Publication Date
Fri Feb 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
Comparison of Some Methods for Estimating the Scheff'e Model of the Mixture
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Because of the experience of the mixture problem of high correlation and the existence of linear MultiCollinearity between the explanatory variables, because of the constraint of the unit and the interactions between them in the model, which increases the existence of links between the explanatory variables and this is illustrated by the variance inflation vector (VIF), L-Pseudo component to reduce the bond between the components of the mixture.

    To estimate the parameters of the mixture model, we used in our research the use of methods that increase bias and reduce variance, such as the Ridge Regression Method and the Least Absolute Shrinkage and Selection Operator (LASSO) method a

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Crossref
Publication Date
Wed Nov 01 2017
Journal Name
Journal Of Engineering
Compressive Strength of Bottle-Shaped Compression Fields of Fiber Reinforced Concrete Members
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Applying load to a structural member may result in a bottle-shaped compression field especially when the width of the loading is less than the width of bearing concrete members. At the Building and Construction Department – the University of Technology-Iraq, series tests on fibre reinforced concrete specimens were carried out, subjected to compression forces at the top and bottom of the specimens to produce compression field. The effects of steel fibre content, concrete compressive strength, transverse tension reinforcement, the height of test specimen, and the ratio of the width of loading plate to specimen width were studied by testing a total of tenth normal strength concrete blocks with steel fibre and one normal s

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