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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 Jun 25 2020
Journal Name
International Journal Of Drug Delivery Technology
Development of a Simple Colorimetric Determination of Dexamethasone
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A simple, environmentally benign, cost-effective, and sensitive colorimetric determination for the pharmaceutical drug dexamethasone sodium phosphate (DXP) has been developed by the formation of a colored complex with fluoranil. The process was sensitive and linear over the range 1 to 40 μg/mL, excellent correlation coefficient 0.9989, recovery% 99.80 ± 1.3, limit of detection (LOD) and limit of quantification (LOQ) were 0.23 and 0.9 μg/mL, respectively, and good RSD ~1.63%. The experimental conditions were optimized after an intensive study. The approach was validated statistically for the quantification of the analyte in its pure and/or pharmaceutical form. Despite the proposed approach is selective, it still can be applied for

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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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Publication Date
Fri Jan 05 2024
Journal Name
Al-academy
Designs treatment of the internal spaces of pharmacies
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The pharmacy is the face for the health buildings and hospitals, The linking professional relationships and functional, it is been from the important places that most people go it, so according to that we must format its interior design in form that suitable with the need of most people use it or work in it, and this the search goal, dashing from the search subject which to hide finding designer treatment for the pharmacies interior spaces, to give share in the functional improvement performance or aesthetic. We define the search goals to share in educate the pharmacist in the effect of interior design for improvement of interior environment, in addition to the search consider as designer trying add to the other trying the interior desig

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Publication Date
Wed May 01 2019
Journal Name
Iop Conference Series: Materials Science And Engineering
Urban renewal of the historic centre of Rusafa
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Abstract<p>The historical centers represent the present of the past, which is embodied in its buildings and spaces, which are places of continuous life bearing the history of the city with all its material and objective dimensions, making it living centers that form an essential part of the body of the city and give it a vision for another time and it represents a cultural heritage that should be preserved and maintained. The research started from the reality that indicates the great change in the land uses of the region and the deterioration of the situation and change in use in addition to the neglect of its role and historical status, the study aims to study the subject of urban renewal of he</p> ... Show More
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Publication Date
Wed Mar 01 2023
Journal Name
Baghdad Science Journal
Sum of Squares of ‘m’ Consecutive Woodall Numbers
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        This paper discusses the Sums of Squares of “m” consecutive Woodall Numbers. These discussions are made from the definition of Woodall numbers. Also learn the comparability of Woodall numbers and other special numbers. An attempt to communicate the formula for the sums of squares of ‘m’ Woodall numbers and its matrix form are discussed. Further, this study expresses some more correlations between Woodall numbers and other special numbers.

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Publication Date
Sun Sep 15 2019
Journal Name
Al-academy
Aesthetic and Functional Dimensions of Environmental Waste in the Products of Students of the Department of Art Education: فردوس خضر الجوفي
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The practice of art is an inevitable result imposed by the circumstances surrounding the human being, as he needs some knowledge associated with raw materials, tools and methods to develop skills in the formation of elements of the work of art in new ways that give a decent artistic appearance to the work of art. Through the exploratory study carried out by the researcher, which included asking the following question to the third grade students, Department of Art Education:

What types of materials are used in handicrafts and from which sources are they obtained? Through the answers, the problem of research was founded as follows:

-Are the products of students of the Department of Art Education in the handicraft material d

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Publication Date
Mon Jan 02 2017
Journal Name
Journal Of Educational And Psychological Researches
The effectiveness of the structural model of learning in the acquisition of geographical concepts among students of the first grade average)
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The current research aims to find out ( the effectiveness of the structural model of learning in the acquisition of geographical concepts at the first grade average students ) , and achieving the goals of research has been formulating the null hypothesis of the following :

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Publication Date
Fri Sep 15 2023
Journal Name
Al-academy
The aesthetics of abstract expressionism and its representations in the artistic productions of the students of the Department of Art Education
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The research section tagged (Aesthetics of Abstract Expressionism and its Representations in the Artistic Products of Students of the Department of Art Education) into four chapters and it included in..
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Publication Date
Tue Nov 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
Proposal of Using Principle of Maximizing Entropy of Generalized Gamma Distribution to Estimate the Survival probabilities of the Population in Iraq
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In this research we been estimated the survival function for data suffer from the disturbances and confusion of Iraq Household Socio-Economic Survey: IHSES II 2012 , to data from a five-year age groups follow the distribution of the Generalized Gamma: GG. It had been used two methods for the purposes of estimating and fitting which is the way the Principle of Maximizing Entropy: POME, and method of booting to nonparametric smoothing function for Kernel, to overcome the mathematical problems plaguing integrals contained in this distribution in particular of the integration of the incomplete gamma function, along with the use of traditional way in which is the Maximum Likelihood: ML. Where the comparison on the basis of the method of the Cen

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Publication Date
Thu Dec 01 2011
Journal Name
Journal Of Economics And Administrative Sciences
application of business managment in the field of football with studuy of the case of spanish club (Real Madrid) و (Barcelona
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Football has progressed from being a ritual and a celebration to become an amateur sport, a professional sport, and now, increasingly, a commercial sport. In the analysis of football business model, the systemic approach should be adopted. If sport is regarded as one of the business sectors, then the application of business system methodology can be fully justified. The interest to create strong football business system calls for the search of the ways of popularizing football business model and boosting the economic potential of its participants. In the research literature tend to ignore the business processes within the sports business. Besides, the systemic approach in football business is usually limited to p

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