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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 Sep 30 2004
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Production of Formaldehyde by Catalytic Conversion of Methanol
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Publication Date
Sun Feb 10 2019
Journal Name
Journal Of The College Of Education For Women
The Sources of the Narrative of Siffin Agreement
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We can conclude that version A is substantially genuine while version B is spurious. an Attempt has been made above to show relevance of this to our understanding of the agreement itself .
The central issue of sunna to which recourse was to be had must of course be connected with development of the meaning of the word sunna from the broader (way of Proceeding ) and (generally agreed practice).
Any sweeping judgements about the invalidity of reports transmitted by shiis or supposed shii are out of place. theestablishment of realistic criteria for the appreciation of early sources for Islamic history is subject which is still in Its infancy

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
new Estimator of the parameter of negative exponential
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the main of this paper is to give a comprehensive presentation of estimating methods namely maximum likelihood bayes and proposed methods for the parameter

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Publication Date
Tue Mar 01 2016
Journal Name
Journal Of Engineering
Analysis of Recorded Inflow Data of Ataturk Reservoir
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Since the beginning of the last century, the competition for water resources has intensified dramatically, especially between countries that have no agreements in place for water resources that they share. Such is the situation with the Euphrates River which flows through three countries (Turkey, Syria, and Iraq) and represents the main water resource for these countries. Therefore, the comprehensive hydrologic investigation needed to derive optimal operations requires reliable forecasts. This study aims to analysis and create a forecasting model for data generation from Turkey perspective by using the recorded inflow data of Ataturk reservoir for the period (Oct. 1961 - Sep. 2009). Based on 49 years of real inflow data

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Publication Date
Sat Dec 01 2012
Journal Name
Journal Of Economics And Administrative Sciences
Impact of Electronic commerce In Imposition of taxes
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That the possibility of imposing a tax on electronic commerce is increasing interest in it by governments in developed and developing countries alike, and there is interest in a logical by governments and bodies of taxation, in particular in developing countries erosion potential tax in the tax base resulting from the adoption of e-commerce if not mutation rules and tax legislation, local and international to take into account this important economic developments and how to keep up, said the combination of the taxation system is the only way to increase revenue needed to finance government spending on goods and services needed by society.

The most important conclusions reached by the rese

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Publication Date
Wed Mar 01 2023
Journal Name
Baghdad Science Journal
Minimum Neighborhood Domination of Split Graph of Graphs
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Let  be a non-trivial simple graph. A dominating set in a graph is a set of vertices such that every vertex not in the set is adjacent to at least one vertex in the set. A subset  is a minimum neighborhood dominating set if  is a dominating set and if for every  holds. The minimum cardinality of the minimum neighborhood dominating set of a graph  is called as minimum neighborhood dominating number and it is denoted by  . A minimum neighborhood dominating set is a dominating set where the intersection of the neighborhoods of all vertices in the set is as small as possible, (i.e., ). The minimum neighborhood dominating number, denoted by , is the minimum cardinality of a minimum neighborhood dominating set. In other words, it is the

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Publication Date
Thu Mar 13 2025
Journal Name
Adab Al-rafidain
Guilt in The Condamned of ALtona of Sartre
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Drama "The Condamned of Altona" shows many different aspects of the 20th century. It contrasts strong, self-assured characters with weak, unsure ones to address absurdism and existentialism. Also, this piece shows the misery of the decade by showing Frantz, one of the play's heroes, taking his own life. Through suicide, disillusionment, and worry, the play depicts the upheaval of the 20th century, which was marred by numerous crises. The play's depiction of the jail and its inmates exemplifies the regret that accompanied the two world wars . Not only does guilt serve as a metaphor for the wrongs done by the Germans, but it also serves as a metaphor for the French inactivity during the occupation. And also the writers who did not devote thei

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Publication Date
Thu Jun 27 2019
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
REVIEW OF OPISTHOGLYPHOUS SNAKES (REPTILIA, OPHIDIA ) OF IRAQ
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Seven species of semi venomous Opisthoglypha snakes (Reptilia, Ophidia) of Iraq are listed with important characteristics in morphology due to geographical and individual variation of species, as well, the confusion in the scales count of Telescopus tessellatus martini (Schmidt, 1939) of Iraq are discussed.

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Publication Date
Fri Feb 01 2013
Journal Name
Proceedings Of The Institution Of Civil Engineers - Ground Improvement
Treatment of collapse of gypseous soils by grouting
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Gypseous soil is a collapsible soil, which causes large deformations in buildings that are constructed on it. Various methods have been used to minimise this effect, such as replacing the gypseous soil or using soil stabilisation (grouting or soil improvement). This study was carried out on four types of gypseous soils that have different properties and various gypsum contents. The testing was carried out on remoulded samples to evaluate the compressibility of gypseous soil under different conditions. The samples were grouted with acrylate liquid. The relationships between the injection pressure and the radius of flow, between time of injection and radius of flow, and between time and quantity of acrylate liquid are investigated on

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Publication Date
Sun Dec 22 2019
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis and Characterizations of Dipeptide Derivative of Gentamicin
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Abstract

      The target derivative are gentamicin linked with L-Val- L-Ala by an ester linkage. These were synthesized by esterification method, which included the reaction of -OH hydroxyl group on (carbon No.5) of gentamicin with the acid chloride of the corresponding dipeptide, The preparation of new derivative of gentamicin involved protected the primary & secondary amine groups of Gentamicin, by Ethylchloroformate (ECF) to give N-carbomethoxy Gentamicin which was used for further chemical synthesis involving the free hydroxyl groups.

Then prepared dipeptide (L-Val- L-Ala) by conventional solution method in present DCC & HoBt then reacted with thionyl

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