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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
Mon Jan 01 2024
Journal Name
Brazilian Dental Science
Evaluation of flexural strength and degree of conversion of temporary crown materials at different aging periods in artificial saliva
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Objective: Evaluate the effects of different storage periods on flexural strength (FS) and degree of conversion (DC) of Bis-Acryl composite and Urethane dimethacrylate provisional restorative materials. Material and Methods: A total of 60 specimens were prepared from four temporary crown materials commercially available and assigned to four tested groups (n = 15 for each group): Prevision Temp, B&E CROWN, Primma Art, and Charm Temp groups. The specimens were stored in artificial saliva, and the FS was tested after 24 h, 7 d, and 14 d. A standard three-point bending test was conducted using a universal testing machine. Additionally, the DC was determined using a Fourier transform infrared spectroscopy (FTIR) device. The data were analyzed st

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Publication Date
Mon Dec 21 2020
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
REVISION OF THE GENUS SINOXYLON DUFTSCHMID, 1825 (COLEOPTERA, BOSTRICHIDAE) WITH NEW RECORD OF SPECIES IN THE MIDDLE OF IRAQ
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Publication Date
Thu Jun 15 2017
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of the effect of preheating on micro leakage of Class II composites Restoration (A comparative in vitro study)
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Background: The aim of this in vitro study was to evaluate and compare the effect of preheating microleakage among three different filler size composites which include Filtektm Z250 micro hybrid, Z250xt Nano hybrid and nanocomposite Z350xt.  in Class II cavity preparation .

Materials and methods: sixty maxillary first premolars were prepared with class II cavities. Samples were divided into three groups according to material used    group A (FiltekZ250 micro hybrid). Group B(Z250xt Nano hybrid). Group C (nanocomposite Z350xt)and each group divided into two subgroups of ten teeth according to temperature of  composite:

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Publication Date
Sat Jun 25 2022
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Al-mağallaẗ Al-šāmilaẗ Li-l-ḥuqūq
The Intent to Harm Others as a Form of Abuse of Rights – A Study in Light of U.S. Law
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In a world of limited space, the owners are always surrounded by others next to them, and, consequently, there is hardly any activity which the owner may exercise on his land which would not affect the other owners. If he builds a building, that building may block the sun's rays or the air from the buildings next to it and owned by other people. And if he runs a business, the lands adjacent to that business may be overburdened with the accompanying noise or traffic. If oil is prospected in a land, the neighboring lands may be deprived of oil or their owners may be exposed to toxic fumes. Hence the importance of researching the intention of harming others, as it is one of the most important forms of abuse in the use of the right (especially

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Publication Date
Mon Jan 01 2018
Journal Name
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Studying of different factors affected in production of amylase enzyme from a local isolate of B. Subtillis A4 bacteria
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The present study aims to detection optimal conditions of production of amylase enzyme from isolate of B. subtillis A4. Nine carbonic sources were represented by starch, maltose, fructose, sucrose, glucose, arabinose, xylose, sorbitol and mannitol) at concentration of 1% for each source. It was found that the best was represented by starch carbonic, which showed higher activity and qualitative activity of 7.647 Unit/ ml and 461.56 Unit/ mg. Ten nitrogen sources were selected, including yeast extract, peptone, trypton, gelatin, urea and meat extract as organic sources Ammonium sulphate, Sodium nitrate, Potassium nitrate and Ammonium chloride as inorganic sources. These sources were added at aconcentration of 0.5% to the production medium. Th

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Publication Date
Mon Jan 01 2018
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Int. J. Agricult. Stat. Sci. V
The role of irrigation management processes and micronutrient fertilization on parameter of growth and yield of two wheat varieties
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Publication Date
Thu May 06 2010
Journal Name
Dirasat, Pure Sciences
A Study of the Effects of the Solar Cycle 22, on the Critical Frequencies of F1 Layer over Baghdad
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This paper aims to study the effects of the long term solar activity on the critical frequencies of ionospheric F1 layer over Baghdad city, during the solar cycle 22, within (1988- 1995). It is found that the critical frequency of this layer is closely related to the sunspots number during the years of the solar cycle 22, at a middle latitude region of the world. The study discussed the effect of sunspot numbers and solar events on the electron densities of F1 layer, which is the most important ionospheric parameter.

Publication Date
Wed Jun 01 2011
Journal Name
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Methods of using the periodic chart in the case of the missing values of the stable AR model (2)
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In this study, we investigate the behavior of the estimated spectral density function of stationary time series in the case of missing values, which are generated by the second order Autoregressive (AR (2)) model, when the error term for the AR(2) model has many of continuous distributions. The Classical and Lomb periodograms used to study the behavior of the estimated spectral density function by using  the simulation.

 

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Using of Index Biological Integrity of Phytoplankton (P-IBI) in the Assessment of Water Quality in Don River Section
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Publication Date
Sat Jul 23 2016
Journal Name
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Effect of cold and hot aqueous extract of garlic on the reproductive performance of immature male mice until puberty
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This study was investigated the role of garlic extracts on the reproductive functions, via the development of immature male mice (25 days old) un l puberty. Immature male mice were divided into 3 groups (n=25). Group 1 "control" was daily administrated with tap water. Group 2 was daily administrated with cold aqueous garlic extract. Group 3 was daily administrated with hot aqueous garlic extract. Each group was randomly consisted of 5 subgroups (n=5/ subgroup) and administrated for different periods i.e, 1, 2, 3, 4 and 5 weeks respectively. Animals were scarified after 24 h from last treatment. Our findings elucidated that, cold and hot aqueous garlic extracts, when administrated at 25 days old (Immature period) have different impact dep

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