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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 Jul 01 2021
Journal Name
Journal Of Mechanical Engineering Research And Developments
Numerical Investigation of Natural Convection Heat Transfer in Partially Filled Porous Enclosure Subjected to Constant Heat
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Steady natural convection in a square enclosure with wall length (L= 20 cm) partially filled by saturated porous medium with same fluid (lower layer) and air (upper layer) is investigated. The conceptual study of the achievements of the heat transfer is performed under effects of bottom heating by constant heat flux (q=150,300,450,600W/m2 ) for three heaters size (0.2,0.14,0.07)m with symmetrically cooling with constant temperature on two vertical walls and adiabatic top wall. The relevant filled studied parameters are four different porous medium heights (Hp=0.25L,0.5L, 0.75L, L), Darcey number (Da1) 3.025×10-8 and (Da2) 8.852×10-4 ) and Rayleigh number range (60.354 - 241.41), (1.304×106 – 5.2166×106 ) for Da1 and Da2 cases respecti

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Publication Date
Thu Aug 07 2025
Journal Name
Journal Of Baghdad College Of Dentistry
In vivo immunohistochemical investigation of the effect of the topical application of growth hormone on the osseointegration of cpTi implant
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Background: Dental implants are a suitable option for the replacement of some or all missing teeth. The successful insertion of a biocompatible material into living tissue with little to no evidence of rejection has revolutionized medicine and dentistry. An increase in bone response was observed with local administration of growth hormone around dental implants. Growth hormone may act as a bone stimulant in the placement of endosseous dental implants and enhances osseointegration. The aim of the study was to evaluate immunohistochemically the effect of the topical application of growth hormone on the osseointegration of cpTi implant. Materials and Methods: Eighty titanium screw implants were inserted in the tibia of the forty adult rabbits.

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Publication Date
Fri Jan 27 2012
Journal Name
Journal Of Huazhong University Of Science And Technology [medical Sciences]
An in vitro investigation into retention strength and fatigue resistance of various designs of tooth/implant supported overdentures
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Publication Date
Sun Jan 01 2017
Journal Name
Rsc Advances
Investigation of the post-annealing electromagnetic response of Cu–Co oxide coatings via optical measurement and computational modelling
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The annealing temperature (200–500 °C) effects of optical frequency response on the dielectric functions of sol–gel derived CuCoOx thin film coatings: experimental and modelling.

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Publication Date
Sun Mar 01 2020
Journal Name
International Journal Of Modern Physics E
Investigation of halo structure of neutron rich 14B, 15C, 19C and 22N nuclei in the two body model
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The two body model of (Core+n) within the radial wave functions of the cosh potential has been used to investigate the ground state features such as the proton, neutron and matter densities, the root mean square (RMS) nuclear proton, neutron, charge and mass radii of unstable neutron-rich 14B, 15C, 19C and 22N nuclei. The calculated results show that the two body model with the radial wave functions of the cosh potential succeeds in reproducing neutron halo in these nuclei.

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Publication Date
Sun Dec 30 2018
Journal Name
Journal Of Engineering
Investigation of R134a Flow Boiling Heat Transfer and Pressure Drop in the Evaporator Test Section of Refrigeration System
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This paper presents an experimental and theoretical analysis to investigate the two-phase flow boiling heat transfer coefficient and pressure drop of the refrigerant R-134a in the evaporator test section of the refrigeration system under different operating conditions. The test conditions considered are, for heat flux (13.7-36.6) kW/m2, mass flux (52-105) kg/m2.s, vapor quality (0.2-1) and saturation temperature (-15 to -3.7) ˚C. Experiments were carried out using a test rig for a 310W capacity refrigeration system, which is designed and constructed in the current work. Investigating of the experimental results has revealed that, the enhancement in local heat trans

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Publication Date
Sun Jan 01 2023
Journal Name
Journal Of Advanced Biotechnology And Experimental Therapeutics
Investigation of the relationship between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase with SARS CoV-2 infections
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SARS-CoV-2 stands for severe acute respiratory syndrome coronavirus 2 which is the causative agent of spreading coronavirus disease 2019 that is known as COVID-19 pandemic, the disease leads to severe acute respiratory illness. Matrix metalloproteinases- 9 (MMP-9) plays several important physiological functions. This enzyme could also be implicated in the "cytokine storm" in some way, which may represent one of the possible scianrios during coronavirus infection, in addition to its role in the mechanism of lung fibrosis on molecular basis.. The tissue inhibitors of metalloproteinase (TIMPs) are well characterized for controlling the activity of MMPs in extracellular matrix remodeling. They also considered as signaling molecules anal

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Publication Date
Fri Aug 30 2024
Journal Name
Iraqi Journal Of Science
Investigation of Flagellum genes FleN and FlgE and Gene Expression of FleN Gene in Pseudomonas Aeruginosa Clinical Isolates
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The opportunistic multidrug resistance pathogen Pseudomonas aeruginosa has one or several flagella, and the numbers of these sophisticated machines are regulated by the flagellar regulator gene FleN. The flagellar hook gene FlgE is important for its synthesis, motility and tolerance to antibiotics. Bacteriahave resistance to antibiotics, especially to cephalosporin beta-lactam antibiotics. For the current study, 102 clinical specimens were collected and identified using routine laboratory tests and confirmed by Vitek-2 compact system.  A total of 33 isolates of P. aeruginosa were identified. The antibiotic susceptibility test was done by the Vitek 2 Compact system. Flagellar gene detected by conventional PCR revealed that the FleN

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Publication Date
Sun Jan 01 2023
Journal Name
Journal Of Advanced Biotechnology And Experimental Therapeutics
Investigation of the relationship between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase with SARS CoV-2 infections
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SARS-CoV-2 stands for severe acute respiratory syndrome coronavirus 2 which is the causative agent of spreading coronavirus disease 2019 that is known as COVID-19 pandemic, the disease leads to severe acute respiratory illness. Matrix metalloproteinases- 9 (MMP-9) plays several important physiological functions. This enzyme could also be implicated in the "cytokine storm" in some way, which may represent one of the possible scianrios during coronavirus infection, in addition to its role in the mechanism of lung fibrosis on molecular basis.. The tissue inhibitors of metalloproteinase (TIMPs) are well characterized for controlling the activity of MMPs in extracellular matrix remodeling. They also considered as signaling molecules anal

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Publication Date
Wed Oct 05 2022
Journal Name
Heat Transfer
Numerical investigation of natural convection in a square enclosure partially filled with horizontal layers of a porous medium
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Abstract<p>Two‐dimensional buoyancy‐induced flow and heat transfer inside a square enclosure partially occupied by copper metallic foam subjected to a symmetric side cooling and constant heat flux bottom heating was tested numerically. Finite Element Method was employed to solve the governing partial differential equations of the flow field and the Local Thermal Equilibrium model was used for the energy equation. The system boundaries were defined as lower heated wall by constant heat flux, cooled lateral walls, and insulated top wall. The three parameters elected to conduct the study are heater length (7 ≤ <italic>ζ</italic> ≤ 20 cm), constant heat flux (150 ≤ <italic>q<</italic></p> ... Show More
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