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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
Mon Nov 08 2021
Journal Name
Caspian Journal Of Environmental Sciences 20 (1),
Evaluate the effect of alcoholic extraction of walnut on gonadal hormones of treated rats
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Publication Date
Thu Apr 13 2023
Journal Name
Sustainability
Experimental Study of the Effect of Tack Coats on Interlayer Bond Strength of Pavement
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The performance and lifetime of the flexible asphalt pavement are mainly dependent on the interfacial bond strength between layer courses. To enhance the bond between layers, adhesive materials, such as tack coats, are used. The tack coat itself is a bituminous material, which is applied on an existing relatively non-absorbent surface to ensure a strong bond between the old and newly paved layer. The primary objective of this study was to evaluate the effects of various types of tack coat materials on interlayer bond strength and to determine the optimal application rate for each type. The tack coat types used in this paper were RC-70, RC-250, and CSS-1h. Both laboratory-prepared and field-constructed hot mix asphalt concrete pavements usin

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Publication Date
Sun Jun 06 2010
Journal Name
Baghdad Science Journal
Algebraic Coincidence Periods Of Self – Maps Of A Rational Exterior Space Of Rank 2
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Let f and g be a self – maps of a rational exterior space . A natural number m is called a minimal coincidence period of maps f and g if f^m and g^m have a coincidence point which is not coincidence by any earlier iterates. This paper presents a complete description of the set of algebraic coincidence periods for self - maps of a rational exterior space which has rank 2 .

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Publication Date
Thu Sep 15 2022
Journal Name
Al-adab Journal
Vocabulary of the modern Russian language from the point of view of stylistic diversity
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Сатья посвящена выделению и описанию функциональных стилей русского языка. В работе будет предствлена стилистическая характеристика заимствованной лексики, которая в некоторых случаях заменяет собственно русские слова, что может приводить к затемнению смысла высказывания, эвфемизации его, кроме того, заимствования заполняют определенные стилистические книши, образовавшиеся в связи со структурны

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Publication Date
Sun Jun 03 2012
Journal Name
Baghdad Science Journal
Approximate Solution of Some Classes of Integral Equations Using Bernstein Polynomials of Two-Variables
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The research aims to find approximate solutions for two dimensions Fredholm linear integral equation. Using the two-variables of the Bernstein polynomials we find a solution to the approximate linear integral equation of the type two dimensions. Two examples have been discussed in detail.

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Publication Date
Sun Aug 25 2024
Journal Name
University Of Samarra
Preparation, diagnosis and testing of the biological ‎activity of new complexes of Schiff bases
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‎ Sixteen new complexes with the general formula [M(L)2(H2O)2] were ‎prepared resulting from the reaction of the two new Schiff base ligands, which ‎are‏: -‏ L1= (E)-5-((2-hydroxybenzylidene)amino)-2-phenyl-2,4-dihydro-3H-pyrazol-3-one)‎ L2 = (E)-5-((2-hydroxy-3-methoxybenzylidene)amino)-2-phenylpyrazolidin-3-one) ‎ ‎ With divalent metal ions (manganese, cobalt, nickel, copper, zinc, cadmium, ‎mercury) and (tetravalent platinum).‎‏ ‏ ‎ Ligands was derived from the reaction of the amine (5-amino-2-phenyl-2,4-‎dihydro-3H-pyrazol-3-one) with Salicylaldehyde and ortho-vanillin, which is ‎linked to the metal ions via the nitrogen atoms are the isomethene group and ‎the oxygen is the hydroxide group of t

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Publication Date
Sat Sep 30 2023
Journal Name
College Of Islamic Sciences
Features of visual formation in the poetry of the poets of the Umayyad era
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Abstract

The Umayyad poets tried to invest all artistic tools in order to achieve a measure of creativity in their texts. The phenomenon of visual composition is breaking the familiar writing system, with the aim of increasing the number of possible connotations. The visual in the Umayyad poetry tries to replace it through expression with the visual image, and its manifestations were manifested by the multiplication of punctuation marks in the body of the poetic text and the tearing of the single poetic line by cutting it into several sentences or repetition.

Keywords: visual formation, poetic writing, Umayyad poetry, recipien

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Publication Date
Wed Jun 01 2022
Journal Name
Political Sciences Journal
The Problem of Political Empowerment of Women with Disabilities in Light of Iraqi Legislation
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Democracy in any country is measured by the cultural, social and economic level reached by women in it in general and women with disabilities in particular, and the extent of their participation in political life and political decision-making. As a result of the patriarchal power that societies have known, including Iraq, history has witnessed multiple types and forms of discrimination against women, which differed from one country to another, this matter has pushed women and since the beginning of the last century the issue of women's rights has been raised at the global, regional and national levels, through holding international conferences and agreements In order to empower women in all social, economic and political fields.

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Publication Date
Mon Aug 30 2021
Journal Name
Al-kindy College Medical Journal
Quality of Life of Parents of Children with Type I Diabetes Mellitus, Baghdad 2017
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Background: Diabetes is defined by the World Health Organization as a metabolic disorder characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. Families are co-regulating systems in which the stresses and strains of one family member affect the well-being of another member of the family. Caregivers of children with chronic illness report experiencing more parental stress than parents of healthy children.

Objective: A descriptive cross-sectional study had been conducted in four centers of endocrine diseases in Baghdad city and data was collected by using self-administered questionnaire regarding qua

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Publication Date
Thu Feb 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
The impact of Communities of practice the knowledge in adoption of, Strategic Change choices
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  The research aimed to diagnose and interpretation of impact nature between Communities of practice dimensions (participation and spreading knowledge, confidence, social capital build) deportation strategic change choices (reengineering business process, business re-structuring, business innovation) in construction companies in the Iraqi Ministry of Construction and Housing, the research tested 4 construction companies working in investing sector in Iraq, the research applied on a sample of 102 persons who participated in Communities of practice distributed in several administrative levels (directors, division directors, project directors and engineers) the research used questionnaire as a main tool for dat

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