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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 Mar 01 2020
Journal Name
Iop Conference Series: Materials Science And Engineering
Evolution and set up the maps for solar radiation of Iraq using Data observation and Angstrom model during monthly July2017
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Abstract<p>The development that solar energy will have in the next years needs a reliable estimation of available solar energy resources. Several empirical models have been developed to calculate global solar radiation using various parameters such as extraterrestrial radiation, sunshine hours, albedo, maximum temperature, mean temperature, soil temperature, relative humidity, cloudiness, evaporation, total perceptible water, number of rainy days, and altitude and latitude. In present work i) First part has been calculated solar radiation from the daily values of the hours of sun duration using Angstrom model over the Iraq for at July 2017. The second part has been mapping the distribution of so</p> ... Show More
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Publication Date
Sun Mar 31 2024
Journal Name
Iraqi Geological Journal
Permeability Prediction and Facies Distribution for Yamama Reservoir in Faihaa Oil Field: Role of Machine Learning and Cluster Analysis Approach
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Empirical and statistical methodologies have been established to acquire accurate permeability identification and reservoir characterization, based on the rock type and reservoir performance. The identification of rock facies is usually done by either using core analysis to visually interpret lithofacies or indirectly based on well-log data. The use of well-log data for traditional facies prediction is characterized by uncertainties and can be time-consuming, particularly when working with large datasets. Thus, Machine Learning can be used to predict patterns more efficiently when applied to large data. Taking into account the electrofacies distribution, this work was conducted to predict permeability for the four wells, FH1, FH2, F

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Publication Date
Tue Oct 22 2019
Journal Name
Scientia Pharmaceutica
Design, Synthesis, and Docking Study of Acyl Thiourea Derivatives as Possible Histone Deacetylase Inhibitors with a Novel Zinc Binding Group
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Histone deacetylase inhibitors with zinc binding groups often exhibit drawbacks like non-selectivity or toxic effects. Thus, there are continuous efforts to modify the currently available inhibitors or to discover new derivatives to overcome these problems. One approach is to synthesize new compounds with novel zinc binding groups. The present study describes the utilization of acyl thiourea functionality, known to possess the ability to complex with metals, to be a novel zinc binding group incorporated into the designed histone deacetylase inhibitors. N-adipoyl monoanilide thiourea (4) and N-pimeloyl monoanilide thiourea (5) have been synthesized and characterized successfully. They showed inhibition of growth of human colon adenoc

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Publication Date
Wed Dec 14 2022
Journal Name
Bulletin Of The Chemical Society Of Ethiopia
Synthesis, characterization, theoretical study and biological evaluation of Schiff base and their La(III), Ce(IV) and UO2(II) complexes
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ABSTRACT. A new three metal complexes of La(III), Ce(IV) and UO2(II) ions have been synthesized based on a Schiff base derived from the condensation of L-histidine and anisaldehyde. All prepared compounds were characterized by different spectroscopic techniques and Density-functional theory (DFT) calculations. The complexes were proposed to have an octahedral structure based on the investigated results. The optimized shape, numbering system, and dipole moment vector of Ligand and La, Ce, and UO2 (1:1) chelates were investigated. The Schiff base ligand and complexes exhibit moderate action against all of the bacteria tested, with P. aeruginosa, Klebsiella sp., and E. faecalis respectively being the order of inhibition.  

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Publication Date
Sun Dec 01 2019
Journal Name
Baghdad Science Journal
Studying the Crystal Structure, Topography, and Anti-bacterial of a Novel Titania (TiO2 NPs) Prepared by a Sol-gel Manner
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In this research, titanium dioxide nanoparticles (TiO2 NPs) were prepared through the sol-gel process at an acidic medium (pH3).TiO2 nanoparticles were prepared from titanium trichloride (TiCl3) as a precursor with Ammonium hydroxide (NH4OH) with 1:3 ratio at 50 °C. The resulting gel was dried at 70 °C to obtain the Nanocrystalline powder. The powder from the drying process was treated thermally at temperatures 500 °C and 700 °C. The crystalline structure, surface morphology, and particle size were studied by using X-ray diffraction (XRD), Atomic Force Microscopy (AFM), and Scanning Electron Microscope (SEM). The results showed (anatase) phase of titanium dioxide with the average grain size

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Publication Date
Wed Mar 09 2022
Journal Name
Journal Of Craniofacial Surgery
The Use of Osseodensification for Ridge Expansion and Dental Implant Placement in Narrow Alveolar Ridges: A Prospective Observational Clinical Study
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The osseodensification (OD) drilling technique was suggested as an alveolar ridge expansion technique, so the aim of this prospective clinical study was to evaluate the amount of bone expansion obtained by the OD drilling technique and its effect on implant stability in patients with narrow alveolar ridges. The width of the alveolar ridge was measured at the crest before and after implant site preparation, whereas the implant stability was measured using Osstell Beacon implant stability quotient (ISQ). The ISQ values were recorded immediately postoperatively and after 16 weeks. Twenty-three patients were included; they received 40 implants. The mean (± standard deviation [SD]) amount of expansion was 1.29 (± 0.41) mm, and the difference b

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Publication Date
Sat Jan 03 2026
Journal Name
Journal Of Molecular Structure
Synthesis, characterization, DFT calculations, molecular docking, ADMET analysis and biological activity of Schiff base metal complexes against colon cancer cells
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Publication Date
Sun Mar 01 2026
Journal Name
Journal Of Molecular Structure
Synthesis, characterization, DFT calculations, molecular docking, ADMET analysis and biological activity of Schiff base metal complexes against colon cancer cells
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Publication Date
Tue Jun 01 2021
Journal Name
Journal Of The College Of Languages (jcl)
A comparative reading of the social and political satire in the works of Abu al-Fadl Zrui Nasrabad and Ahmad Rajab (The tadhk: خوانش تطبیقی طنز اجتماعی – سیاسی در آثار ابوالفضل زرویی نصرآباد و احمد رجب(مورد مطالعه: تذکرة المقامات زرویی و نصف كلمة احمد رجب)
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           Satire is genre of the literary arts that has always been the source of human interest. Because  it is difficult to accept direct criticism, Satire appears as a literary tool in which vices, follies, abuses and shortcomings are held up to ridicule, with the intent of shaming individuals, corporations, government, or society itself into improvement. A satirical critic usually employs irony to attain this goal. Although satire is usually meant to be humorous, its greater purpose is often profitable social criticism, using wit to draw at

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Publication Date
Tue Apr 11 2023
Journal Name
Indonesian Journal Of Chemistry
Synthesis of Co (ll), Ni (ll), Cu (ll), Pd (ll), and Pt (lV) Complexes with 14, 15, 34, 35-Tetrahydro-11 H, 31 H-4, 8-diaza-1,3 (3,4)-ditriazola-2,6 (1,4)-dibenzenacyclooctaphane-4,7-dien-15, 35-dithione, and the Thermal Stability of Polyvinyl Chloride Modified Complexes
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In the current endeavor, a new Schiff base of 14,15,34,35-tetrahydro-11H,31H-4,8-diaza-1,3(3,4)-ditriazola-2,6(1,4)-dibenzenacyclooctaphane-4,7-dien-15,35-dithione was synthesized. The new symmetrical Schiff base (Q) was employed as a ligand to produce new complexes comprising Co(II), Ni(II), Cu(II), Pd(II), and Pt(II) metal-ions at a ratio of 2:1 (Metal:ligand). There have been new ligands and their complexes validated by (FTIR), (UV-visible), 1H-NMR, 13C-NMR, CHNS, and FAA spectroscopy, Thermogravimetric analysis (TG), Molar conductivity, and Magnetic susceptibility. The photostabilization technique to enhance the polymer was also used. The ligand Q and its complexes were mixed in 0.5% w/w of polyvinyl chloride in tetrahydrofuran

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