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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 May 17 2023
Journal Name
Journal Of Engineering
Multicomponent Biosorption of Heavy Metals Using Fluidized Bed of Algal Biomass
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This paper aims to study the biosorption for removal of lead, cadmium, copper and arsenic ions using algae as a biosorbent. A series of experiments were carried out to obtain the breakthrough data in a fluidized bed reactor. The minimum fluidization velocities of beds were found to be 2.27 and 3.64 mm/s for mish sizes of 0.4-0.6 and 0.6-1 mm diameters, respectively. An ideal plug flow model has been adopted to characterize the fluidized bed reactor. This model has been solved numerically using MATLAB version 6.5. The results showed a well fitting with the experimental data. Different operating conditions were varied: static bed height, superficial velocity and particle diameter. The breakthrough curves were plotted for each metal. Pb2+ s

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Publication Date
Mon Sep 30 2019
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Development of East Baghdad Oil Field By Clusters of Horizontal Wells
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There are varieties of reasons lead for drilling horizontal wells rather than verticals. Increasing the recovery of oil, especially from thin or tight reservoir permeability is the most important parameter. East Baghdad oil field considered as a giant field with approximately more than 1billion barrel of a proved reserves accompanying recently to low production rate problems in many of the existing wells.    It is important to say that presence of of  horizontal wells in East Baghdad field especially by converting some of already drilled wells by re-entry drilling horizontal sections may provide one of best solutions for the primary development stage in East Baghdad field which may be followed by drilling new horizont

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Publication Date
Mon Oct 01 2012
Journal Name
Journal Of Engineering
Prediction of Smear Effect on the Bearing Capacity of Driven Piles
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This paper deals with prediction the effect of soil re-moulding (smear) on the ultimate bearing capacity of driven piles. The proposed method based on detecting the decrease in ultimate bearing capacity of the pile shaft (excluding the share of pile tip) after sliding downward. This was done via conducting an experimental study on three installed R.C piles in a sandy clayey silt soil. The piles were installed so that a gap space is left between its tip and the base of borehole. The piles were tested for ultimate bearing capacity according to ASTM D1143 in three stages. Between each two stages the pile was jacked inside the borehole until a sliding of about 200mm is achieved to simulate the soil re-moulding due to actual pile driving. The re

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Publication Date
Tue Jan 01 2019
Journal Name
Aip Conference Proceedings
Improvement of electrical features of SnO2 based varistor doped with Al2O3
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One of the important objectives of the varistor is for a sustainable environment and reduce the pollution resulting from the frequent damage of the electrical devices and power station waste. In present work, the influence of Al2O3 additives on the non –linear electrical features of SnO2 varistors, has been investigated, where SnO2 ceramic powder doped with Al2O3 in three rates (0.005, 0.01, and 0.05), the XRD test improved that SnO2 is the primary phase, while CoCr2O4, and Al2O3 represent the secondary phases. The electrical tests of all prepared samples confirmed that the increasing of Al2O3 rates and sintering temperature improves and increase the electrical features, where the best results obtained at Al2O3 (0.05) and 1000℃, the non

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Publication Date
Wed Apr 25 2012
Journal Name
The Nineteenth Scientific Conference The College Of Education \al-mustansiriyah University
Solution of Ordinary BVP's of Eighth Order Using Osculatory Interpolation Technique
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The aim of this paper is to present method for solving ordinary differential equations of eighth order with two point boundary conditions. We propose two-point osculatory interpolation to construct polynomial solution.

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Publication Date
Fri Sep 30 2022
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Kinetic Study of Transesterification Reaction of Edible Oil Using Heterogenous Catalyst
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AlPO4 solid acid catalyst was prepared in order to use it in transesterification reaction of edible oil after supporting it with tungsten oxide. The maximum conversion of edible oil was obtained 78.78% at catalyst concentration (5gm.), temperature 70°Ϲ, 30/1 methanol/edible oil molar ratio, and time 5hr. The study of kinetics of the transesterification reaction of edible oil indicates that the reaction has an order of 3/2, while the value of activation energy for  transesterification reaction is 51.367 kJ/mole and frequency factor equal 26219.13(L/ mol.minute).

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Publication Date
Sat Jul 03 2010
Journal Name
Baghdad Science Journal
Isochronal Studies of the Structural and Electrical Properties of CdTe Films
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The paper reports the influence of annealing temperature under vacuum for one hour on the some structural and electrical properties of p-type CdTe thin films were grown at room temperature under high vacuum by using thermal evaporation technique with a mean thickness about 600nm. X-ray diffraction analysis confirms the formation of CdTe cubic phase at all annealing temperature. From investigated the electrical properties of CdTe thin films, the electrical conductivity, the majority carrier concentration, and the Hall mobility were found increase with increasing annealing temperatures.

Publication Date
Mon Jan 01 2018
Journal Name
Ournal Of Advanced Research In Dynamical And Control System
Effect of magnetic field on peristaltic transport of bingham plastic fluid
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Publication Date
Sun Sep 01 2019
Journal Name
Civil Engineering Journal
Effect of PolyPhosphoric Acid on Rutting Resistance of Asphalt Concrete Mixture
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The action of high repeated trucks load associated with dramatically elevated ambient temperatures leads to the most harmful distress in asphalt pavements occurred in Iraq known as rutting. Essentially, it is produced from the accumulation of irrecoverable strains, which mainly occurred in the asphalt layers. That visually demonstrated as a longitudinal depression in the wheel paths as well as small upheavals to the sides. Poly Phosphoric Acid (PPA) has been used as a means of producing modified asphalt binders and the interest to use it has increased in recent years. The PPA provides modified asphalt binder, which is relatively cheaply produced compared to polymer-modified asphalt. In this paper, PPA was used by three-percentages 1

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Publication Date
Sun Mar 05 2017
Journal Name
Baghdad Science Journal
Histomorphological study of uropygial gland of pekin duck (Anas platyrhnchos domesticus)
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The study included 20 birds of Pekin duck (Anas platyrhnchos domesticus) for study the histological of uropygial gland (10 males + 10 females), the weights were between (1411-1582 gm) for males and (1350-1980 gm) female. Routine Histological Techniques was done and stained by Hematoxylin and Eosin (H&E), Periodic Acidic Schiff (PAS), Masson's trichrome stains. Histological sections of the uropygial gland of Pekin ducks showed that the gland consist of the capsule, parenchyma, isthmus and uropygial papillae. The capsule consist of Dense irregular connective tissue. The mean thickness of capsule around the gland lobes were (56.321?17.206µm) and around the uropygial papillae were (67.208?14.996 µm). The capsule tissues continuous in betwe

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