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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
Thu Dec 11 2025
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Circulating B-cell activating Factor in Multiple Myeloma Patients and Its Correlations with Serum Levels of β2-Microglobulin and Interleukin-6
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Background: Multiple myeloma (MM) is characterized by clonal proliferation of malignant plasma cells within the bone marrow. In most patients, monoclonal immunoglobulin heavy chains or light chains are produced and are associated with organ dysfunction. The growth factor B-cell activating factor (BAFF) plays an important role in the pathogenesis of multiple myeloma due to its ability to promote B-cell survival, expansion, and differentiation. Objective:  to measure the circulatory level of B-cell activating factor in multiple myeloma patients in relapsed and remission states and explore its possible correlations with the clinical staging, β2-microglobulin, and interleukin-6. Methods: This cross-sectional study was performed on 60

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Publication Date
Sat Apr 01 2023
Journal Name
Baghdad Science Journal
Synthesis, Spectroscopy of New Lanthanide Complexes with Schiff Base Derived From (4-Antipyrinecarboxaldehyde with Ethylene Di-Amine) and Study the Bioactivity
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The study involved preparing a new compound by combining Schiff bases generated from compounds for antipyrine, including lanthanide ions (lanthanum, neodymium, erbium, gadolinium, and dysprosium). The preparation of the ligand from condensation reactions (4-antipyrinecarboxaldehyde with ethylene di-amine) at room temperature, and was characterization using spectroscopic and analytical studies ( FT-IR, UV-visible spectra, 1H-NMR, mass spectrometry, (C.H.N.O), thermogravimetric analysis (TGA), in addition to the magnetic susceptibility and conductivity measurement of the synthesis complexes, among the results we obtained from the tests, we showed that the ligand behaves with the (triple Valence) lanthanide ions, the multidentate

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Publication Date
Fri Jan 13 2023
Journal Name
World Academy Of Sciences Journal
Potential effects of miR‑146 expression in relation to malondialdehyde as a biomarker for oxidative damage in patients with breast cancer
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Tue Sep 10 2024
Journal Name
Journal Of Mathematics And Computer Science
The role of human shield in prey‎, ‎crop-raiders and top predator species in southwestern Ethiopia's coffee forests‎: ‎a modeling study
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In this work, we have developed a model that describes the relationships between top predators (such as tigers, hyenas, and others), crop raiders (such as baboons, warthogs, and deer), and prey (such as deer) in the coffee forests of southwest Ethiopia. Various potential equilibrium points are identified. Additionally, the model's stability in the vicinity of these equilibrium points is examined. An investigation of the model's Hopf bifurcation is conducted concerning several significant parameters. It is found that prey species may be extinct due to a lower growth rate and consumption by top predators in the absence of human interference in the carrying capacity of prey. It is observed that top predators may be extinct due to human interfe

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Tue Aug 22 2023
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Experimental and finite element analysis of reinforced concrete multi-cell box girders retrofitted with carbon fiber reinforced polymer strips under torsion
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Publication Date
Sat Sep 30 2023
Journal Name
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Poetics and its functions In the book of "The Magic and Poetry" by Lisan Al-Din Ibn Al-Khatib (776 AH
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Studies on membrane stability and extraction of ciprofloxacin from aqueous solution using pickering emulsion liquid membrane stabilized by magnetic nano-Fe2O3
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Multicomponent Equilibrium Isotherms and Kinetics Study of Heavy Metals Removal from Aqueous Solutions Using Electrocoagulation Combined with Mordenite Zeolite and Ultrasonication
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Combining different treatment strategies successively or simultaneously has become recommended to achieve high purification standards for the treated discharged water. The current work focused on combining electrocoagulation, ion-exchange, and ultrasonication treatment approaches for the simultaneous removal of copper, nickel, and zinc ions from water. The removal of the three studied ions was significantly enhanced by increasing the power density (4–10 mA/cm2) and NaCl salt concentration (0.5–1.5 g/L) at a natural solution pH. The simultaneous removal of these metal ions at 4 mA/cm2 and 1 g NaCl/L was highly improved by introducing 1 g/L of mordenite zeolite as an ion-exchanger. A remarkable removal of heavy metals was reported

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Tue May 17 2022
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