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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 15 2022
Journal Name
Al-adab Journal
Metaphors and comparisons as a means of rethinking the phenomena of the surrounding world
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The article characterizes metaphors and comparisons as a means of rethinking the phenomena of the surrounding world; two directions are named within which metaphors and comparisons are studied: 1) the linguo-classification direction combines several classifications of metaphors and comparisons, which are basically focused on comparing two denotations through the meanings of word forms that are part of the trope; 2) the theoretical and conceptual direction is associated with the concept of conceptual displacement and is the basis of the theoretical and methodological study of metaphor and comparison, i.e. the modern theory of metaphor is being formed; The main attention is focused on the comparative concept of Aristotle, which postul

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Publication Date
Fri Jan 01 2016
Journal Name
Iraqi Journal Of Agricultural Sciences
Influence of cytokinins and sucrose concentrations on bulblet characters of In Vitro Hippeastrum Hybridum
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Publication Date
Fri Sep 24 2021
Journal Name
Indonesian Journal Of Chemistry
Molecular Imprinted of Nylon 6 for Selective Separation of Procaine by Solid-Phase Extraction
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The study is based on the selective binding ability of the drug compound procaine (PRO) on a surface imprinted with nylon 6 (N6) polymer. Physical characterization of the polymer template was performed by X-ray diffraction and DSC thermal analysis. The imprinted polymer showed a high adsorption capacity to trap procaine (237 µg/g) and excellent recognition ability with an imprinted factor equal to 3.2. The method was applied to an extraction column simulating a solid-phase extraction to separate the drug compound in the presence of tinoxicam and nucleosimide separately and in a mixture of them with a recovery rate more than the presence of tinoxicam and nucleosimide separately and in a mixture of them with a recovery rate of more t

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Publication Date
Wed Jan 01 2014
Journal Name
Iosr Journal Of Applied Chemistry (iosr-jac)
Synthesis and Characterization of new metals complexes of [N-(4- chlorobenzoylamino)-thioxomethyl]valine (cbv)
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A new ligand [N-(4-chlorobenzoyl amino) -thioxomethyl] valine (cbv) is synthesized by reaction of 4- chloro benzoyl iso thio cyanate with valine acid. The ligand is Characterized by elemental analysis ,FT-IR, and 13C 1H NMR spectra, some transition metals complex of this ligand were prepared and Characterized by FTIR , UV-Visible spectra , conductivity measurement's ,magnetic susceptibility , atomic absorption and determination of molar ratio (M:L), from results obtained , the following formula [M(cbv)2] where M+2 =Mn, Fe ,Co , Ni , Cu,Zn,Cd, and Hg and the proposed molecular structure for these complexes as tetrahedral geometry, except copper complex is have square planer geometry

Publication Date
Thu Jan 20 2011
Journal Name
Journal Of Planner And Development
Architectural void is a revolution in the formation of the facades of digital architecture
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Architecture has evolved through the ages as forms, relationships, materials and mechanisms according to the data of each era and up to the era of digital technology, where the change in proportions and aesthetic dimensions of contemporary architectural formation due to the capabilities of digitization has created innovative plastic properties using the void formation in the facades and the introduction of void as a formative and aesthetic element, which led to The emergence of new creative concepts and ideas that contradict traditional ideas and are consistent with the spirit of the times, led to a revolution in the world of architectural form at the level of (architectural ideas and the generation of shapes, materials and construction

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Publication Date
Mon Feb 14 2022
Journal Name
Journal Of Educational And Psychological Researches
The Effect of S.N.I.P.S Strategy on the Achievement of Fifth Grade Students in Geography
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The present research aims at identifying the impact of S.N.I.P.S strategy on the achievement of fifth grade students in natural geography

For the purpose of verifying the objective of the research, the researcher put the following zero hypothesis: There is no statistically significant difference at the level of (0.05) between the mean score of experimental group who study according to the (S.N.I.P.S) strategy, and the mean score of control group who study according to the traditional method in the achievement test.

In order to verify the validity of this null hypothesis, the researcher adopted the experimental method. Two groups of (60) fifth grade literary students were collecte

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Publication Date
Wed Nov 07 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Oral health status of patients after replacement of removable partial dentures after three years
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Objective(s): To assess the effect of removable partial dentures on the abutment teeth in comparison with that of the
remaining dentition, and to investigate the effect of regular check up on periodontal health for patients using this
type of prosthesis.
Methodology: One hundred patients wearing removable partial dentures for at least three years included in the
study. Teeth used as direct or in direct retainers for the removable partial denture were considered as the study
group, while the remaining dentition in the same jaw was considered as the control group. The following periodontal
parameters were registered for each tooth, plaque and gingival indices, clinical attachment level and tooth mobility.
Patients were

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Publication Date
Wed Dec 29 2021
Journal Name
Al-khwarizmi Engineering Journal
Evaluation of the Main Causes of Diesel Engine Injector Failure using Fault Tree Analysis
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The maintenance of the diesel engine parts in any electric power station contains many problems that lead to stopping. Several reasons lead to such problems; these reasons should be analyzed and evaluated in order to eliminate their effects. This paper is based on evaluation of the main causes that lead to diesel engine injector failure as a main part of electric power stations, using fault tree analysis (FTA). The FTA is the most broadly utilized strategies in the industrial area to perform reliability analysis of complex designing frameworks. A fault tree is a logical representation of the relationship of basic events that lead to a given unwanted event (i.e., top event).

Starting with introducing the FTA and how it could be uti

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Publication Date
Sun Sep 04 2011
Journal Name
Baghdad Science Journal
Study the Effect of Ocimum basilscm oil in the Sensory properties of Laboratory Biscuit
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The study aims at showing the effect of basil oil on the sensory properties of the laboratory biscuits. the results show the sensory valuation before and after the storage. the (A4) equation exceeds 15% of T exchange (3 , 4 , 5 g. basil 19 , 55 g . fats )in most of the studied sensuous qualities. Then, the (A5) equation of 20% exchange percentage (4.60g. basil oil + 18.40g. fats). Then, the (A3) equation of 10% exchange percentage (2.30g. basil oil + 20.70g. fats). Then the (A2) equation of 5% exchange percentage (1.5g. basil oil + 21.85g. fats). Finally, the control equation (A1) received the lower value of sensuous evaluation and general acceptance. Abstract differences also appeared at denotation level 0.05 between the (A2)

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Publication Date
Thu Dec 01 2011
Journal Name
Journal Of Engineering
EFFECT OF COOLING RATE ON MECHANICAL PROPERTIES OF EUTECTIC AND HYPOEUTECTIC Al-Si ALLOYS
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In this research the effect of cooling rate and mold type on mechanical properties of the eutectic
and hypoeutectic (Al-Si) alloys has been studied. The alloys used in this research work were (Al- 12.6%Si
alloy) and (Al- 7%Si alloy).The two alloys have been melted and poured in two types of molds with
different cooling rates. One of them was a sand mold and the other was metal mold. Mechanical tests
(hardness, tensile test and impact test) were carried out on the specimens. Also the metallographic
examination was performed.
It has been found that the values of hardness for the alloys(Al-12.6%Si and Al-7%Si) which poured in
metal mold is greater than the values of hardness for the same alloy when it poured in a heated

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