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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 May 31 2012
Journal Name
Al-khwarizmi Engineering Journal
An Experimental Study on the Effect of Shape and Location of Vortex Generators Ahead of a Heat Exchanger
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An experimental study is carried out on the effect of vortex generators (Circular and square) on the flow and heat transfer at variable locations at (X = 0.5, 1.5, 2.5 cm) ahead of a heat exchanger with Reynolds number ranging from 62000< Re < 125000 and heat flux from 3000 ≤ q ≤ 8000 W/m2 .

In the experimental investigation, an apparatus is set up to measure the velocity and temperatures around the heat exchanger.                     

The results show that there is an effect for using vortex generators on heat transfer. Also, heat transfer depends on the shape and location. The circular is found t

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Publication Date
Fri Mar 30 2001
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Construction of Nomograms Describing the Effect of Different Variables on the Behavior of a KCl/Polymer Drilling Fluid
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Publication Date
Tue Jan 01 2019
Journal Name
Desalination And Water Treatment
Numerical modeling of performance of olive seeds as permeable reactive barrier for containment of copper from contaminated groundwater
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Publication Date
Fri Jan 08 2016
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Effect of Aqueous Leaves Extract of Coriandrum sativum on Histological Structure and Liver Function of Male Albino mice
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Medicinal plants are used to treat various diseases although little is known about their toxicity. Coriandrum sativum is one of the most commonly plants that is used to treat several physiological disorders. Thus, this study was conducted to evaluate the effect of aqueous extract of C. sativum on the structure and function of liver in male albino mice. Thirty male mice were randomly divided into three groups: Group 1 untreated (control), Group 2 and 3 were administrated orally with the aqueous extract of the plant at dose 125 and 250 mg/kg. b. w. For 30 days. The effect of the extract on liver weights, biochemical parameters as well as histological study were assessed. There were no significant difference (P>0.05) observed in relative organ

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Publication Date
Sat Jan 01 2022
Journal Name
Agricultural Engineering
The Effect of Adjuvant Concentration on Changes of Spray Characteristics and Spraying Parameters for Selected Types of Nozzles
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Abstract<p>The paper presents the results of the research on the influence of the adjuvant concentration on the size of the drops produced by the spray nozzles of agricultural sprayers. For the tests, adjuvant Normaton with the composition of total nitrogen, amide nitrogen (N-NH<sub>2</sub>) and phosphorus pentoxide (P<sub>2</sub>O<sub>5</sub>) was used. The adjuvant was added to the water taken from the municipal water supply system of the city of Lublin. The tests were carried out for three concentrations, i.e. 75%, 100%, and 125% of the adjuvant concentration recommended by the manufacturer, and water without the adjuvant. The surface tension of water with adjuva</p> ... Show More
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Publication Date
Mon Oct 01 2018
Journal Name
The Saudi Dental Journal
Evaluation of some mechanical properties of a new silicone elastomer for maxillofacial prostheses after addition of intrinsic pigments
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Objective: The approximate life span of a silicone maxillofacial prosthesis is as short as1.5–2 years of clinical service, then a new prosthesis should be fabricated. The most common reasonfor re-making the prosthesis is silicone mechanical properties degradation. The aim of this studywas to assess some mechanical properties of VST-30 silicone for maxillofacial prostheses after addi-tion of intrinsic pigments.Methods: Two types of intrinsic pigments (rayon flocking and burnt sienna); each of them wasincorporated into silicone. One hundred and twenty samples were prepared and split into 4 groupsaccording to the conducted tests (tear strength, hardness, surface roughness, and tensile strengthand elongation percentage) with 30 samples for ea

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Publication Date
Fri Dec 15 2023
Journal Name
Al-academy
The extent of theatrical and musical arts contribute to the diagnosis And treatment of psychological problems Inmates of
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 The research aims to identify the extent to which the theatrical and musical arts contribute to diagnosing and treating psychological problems among the residents of children’s villages in Jordan, and the methodologies adopted by the theatrical and musical arts to achieve this. It moves on to prove the theory that theatrical and musical arts have an impact on improving the psychology of the residents of children’s villages in Jordan by reviewing the theories and opinions that address the subject from a scientific point of view proven by experiences and expertise. The research took place in the period between (2019-2020), and the spatial limits came within the (SOS) children's villages in Jordan. The importance of the research is to

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Publication Date
Wed Oct 14 2020
Journal Name
Plant Archives
EVALUATION OF THE EFFICIENCY OF SOME CHEMICAL (FYLEX), NANOPARTICLES (MGO) AND BIOLOGICAL FACTORS IN INHIBITING OF ASPERGILLUS FLAVUS
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The Fylex extract exert a high inhibition effect against A . flavus growth on PDA medium, as the fungus growth was completely inhibited by 100% at a concentration of 0.2 and 0.3% of studied extract, while the lowest inhibition percentage (71%) was found at a concentration of 0.1%. Whereas magnesium oxide nanoparticles showed the highest inhibition ratio of A. flavus (100%) was detected at 0.2% and the lowest inhibition ratio (81.66%) was at concentration 0.5%. Moreover, the addition of G. lucidum powder to PDA medium with a concentration of 2.5 mg increased the inhibition rate of A. flavus growth which was 54.4%, while the lowest inhibition ration (18.22%) was found at a concentration of 1000 mg. The milky liquid (brocade milk) of Calotropi

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Publication Date
Fri May 17 2019
Journal Name
Biochem. Cell.arch
THE EFFICACY OF GOLD NANOPARTICLES IN INHIBITING THE TOXICEFFECT OF TAMOXIFEN ON THE KIDNEYS OF MALE ALBINO MICE
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Publication Date
Fri Jan 03 2020
Journal Name
Annals Of Tropical Medicine And Public Health
Genomic Fingerprinting of Interleukin IL-12RB2 of Nasal Mucosal Stem Cells in Nasal Polyposes (NPs) of Iraqi Patients
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The inflammatory reactions cause nasal polyposes (NPs), which contained the paranasal sinuses and the nasal mucous membrane. They consist of recurrent multiple masses originating in the paranasal sinuses then spread from the middle meatus to the nasals cavity, which leads to the nasal blockage that causes the restriction of airflow to the olfactory area. This study aims at clarifying the role of IL-12RB2 polymorphism by using PCR technology in nasal mucosal stem cells in nasal polyps of Iraqi patients and use it as a biomarker. Fifty-eight cases of this study are referred to as nasal surgery, which selected from Dept.of Otolaryngology, Baghdad City, Iraq from May 2013 to January 2014. They were grouped into Control group (022 samples

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