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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
Tue Jul 20 2021
Journal Name
Materials Science Forum
Investigation into the Distribution of Erosion-Corrosion in the Furnace Tubes of Oil Refineries
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Crude oil is one of the most important sources of energy in the world. To extract its multiple components, we need oil refineries. Refineries consist of multiple parts, including heat exchangers, furnaces, and others. It is known that one of the initial operations in the refineries is the process of gradually raising the temperature of crude oil to 370 degrees centigrade or higher. Hence, in this investigation the focus is on the furnaces and the corrosion in their tubes. The investigation was accomplished by reading the thickness of the tubes for the period from 2008 to 2020 with a test in every two year, had passed from their introduction into the work. Where the thickness of more than one point was measured on each tube in the sa

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Publication Date
Sun Feb 10 2019
Journal Name
Iraqi Journal Of Physics
Investigation of the nuclear structure of 84-108Mo isotopes using Skyrme-Hartree-Fock method
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Over the last few decades the mean field approach using selfconsistent
Haretree-Fock (HF) calculations with Skyrme effective
interactions have been found very satisfactory in reproducing
nuclear properties for both stable and unstable nuclei. They are
based on effective energy-density functional, often formulated in
terms of effective density-dependent nucleon–nucleon interactions.
In the present research, the SkM, SkM*, SI, SIII, SIV, T3, SLy4,
Skxs15, Skxs20 and Skxs25 Skyrme parameterizations have been
used within HF method to investigate some static and dynamic
nuclear ground state proprieties of 84-108Mo isotopes. In particular,
the binding energy, proton, neutron, mass and charge densities

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Publication Date
Tue Sep 03 2024
Journal Name
Tropical Parasitology
Investigation the effect of the aqueous extract of Chara vulgaris (L.) on visceral leishmaniasis
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Abstract<sec><title>Background:

Visceral leishmaniasis (VL) is a parasitic disease that affects public health. It is described by weight reduction, irregular fever bouts, anemia, and amplification of the spleen and liver.

Materials and Methods:

Three concentrations (15.6, 31.2, and 62.5 μg/mL) were used to find the potency of an aqueous extract ofChara vulgarisalgae in the treatment of VL. A cytotoxicity assay was performed to show the cytotoxic effect of this extract on human cells. High-performance liquid chromatography (HPLC) test was done to determine the active compounds in the ext

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Publication Date
Tue Sep 03 2024
Journal Name
Tropical Parasitology
Investigation the effect of the aqueous extract of Chara vulgaris (L.) on visceral leishmaniasis
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Abstract<sec><title>Background:

Visceral leishmaniasis (VL) is a parasitic disease that affects public health. It is described by weight reduction, irregular fever bouts, anemia, and amplification of the spleen and liver.

Materials and Methods:

Three concentrations (15.6, 31.2, and 62.5 μg/mL) were used to find the potency of an aqueous extract ofChara vulgarisalgae in the treatment of VL. A cytotoxicity assay was performed to show the cytotoxic effect of this extract on human cells. High-performance liquid chromatography (HPLC) test was done to determine the active compounds in the ext

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Publication Date
Thu Nov 01 2018
Journal Name
Colloids And Surfaces B: Biointerfaces
Green synthesis of silver nanoparticles using turmeric extracts and investigation of their antibacterial activities
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Publication Date
Thu Feb 07 2019
Journal Name
Iraqi Journal Of Laser
Evaluation of Low Level Laser Therapy using 785 nm Diode Laser on the Enhancement of Chronic Wound Healing
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Low-intensity laser irradiation has been explored as an alternative, non-invasive method to encourage chronic wounds to heal. This study aimed to evaluate the effects of low level laser therapy (biostimulation) using semiconductor diode laser with wavelength (785 nm) on the enhancement of chronic wound healing. Fifty patients with chronic wounds were selected to be treated with Low Level Laser Therapy. Their ages ranged between 1 to 76 years. The wound sites were distributed in the lower limb, upper limb, trunk , perineum and head (70%,14%,12%,2%,2%, respectively). Application of laser therapy by noncontact method few millimeters from the skin for 15 minutes per one session twice weekly for two months ; ie,16 sessions for each patient. R

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Publication Date
Thu Nov 01 2018
Journal Name
Journal Of Craniofacial Surgery
Novel Application of Platelet-Rich Fibrin as a Wound Healing Enhancement in Extraction Sockets of Patients Who Smoke
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The objectives of this study were to assess the potential of platelet-rich fibrin (PRF) on acceleration of soft tissue healing after tooth extraction and to evaluate its effectiveness in reducing the prevalence of dry socket among smoker patients. Twenty smoker male patients aged (18–72) years with multiple teeth extraction were participated in this clinical research. They underwent trans-alveolar extraction of 40 teeth. The extraction sockets were divided in each patient into 2 groups: the study group in which extraction sockets were treated with PRF and the control group: in which extraction sockets left to heal naturally without PRF. Platelet-rich fibrin enhan

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Publication Date
Fri Aug 17 2018
Journal Name
Research On Chemical Intermediates
Sensitization of Mn with CdS nanoparticles via electrochemical deposition technique for photocurrent enhancement of nanomaterial’s-sensitized photoelectrochemical cells
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Publication Date
Mon Apr 03 2023
Journal Name
Journal Of Educational And Psychological Researches
The Effectiveness of a Developed Unit in The Arabic Language Textbook for The Enhancement of 21st Century Skills
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Abstract

This research aims to develop a unit as part of a sixth-grade Arabic language textbook and measure its effectiveness in the development of twenty-first-century skills of female students. The author adopted the experimental approach with a quasi-experimental design of the pre-post single-group. A list of the major skills was derived from the framework for the 21st-century skills of the mother tongue that was developed by the Partnership for 21st-Century Skills and reviewed and adjusted by some specialists. According to their views, the unit was developed. The study targeted 15 sub-skills falling under three main skills. The results of the study showed the effectiveness of the developed unit in the develo

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Publication Date
Wed May 01 2024
Journal Name
Solid State Ionics
Enhancement of ionic conductivity and electrochemical stability of PVA/HPMC/PANI/CuSO4 gel polymer for rechargeable batteries electrolytes
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Gel polymer electrolytes (GPEs) have drawn a lot of interest due to their special qualities, which include high conductivity that is comparable to liquid electrolytes, excellent mechanical stability, and high flexibility. Using the solution casting approach, we have synthesized copper ion conducting gel polymer electrolyte (GPE) films made of polyvinyl alcohol (PVA) as the polymer host. An ionic salt, copper sulphate (CuSO 4 ), and a plasticizing solvent, PANI/ [BMIM] [BF 4 ] polyionic liquid, were employed. The structural, electrical, and electrochemical properties of the GPE films were carefully examined. The significant XRD crystalline peak decreased and disappeared upon the addition of PANI/[BMIM] [BF 4 ] polyionic liquid, suggesting th

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