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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
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Biodiversity of Rotifera and Cladocera in the upper region of Euphrates River- Iraq
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Five representative sampling stations were selected in upper region of Euphrates river. Bimonthly sampling were collected from December 2000 to December 2001. Rotifera showed high density in December 2000 while high density of cladocera which recorded in October .The results of relative abundance index showed that rotifera: Polyarthera dolichoptera , Keratella cochlearis , K. valga, Cephalodella auriculata and cladocera: Bosmina longirostris , B.coregoni ,Chydorus spharicus, were more abundant in study stations. The results of constancy index showed 4 taxa belonged to rotifera and 2 taxa belonged to cladocera which were considered constant in the Euphrates river, where the other species varied between accessory and accidental speci

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Publication Date
Wed May 01 2019
Journal Name
Proceedings Of International Structural Engineering And Construction
FLEXURAL DUCTILITY OF STRUCTURAL CONCRETE MEMBERS SUBJECTED TO LIMITED CYCLES OF REPEATED LOADING
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For structural concrete members that may expose to serious earthquake, overload or accident impact, the design of ductility must be given the same importance as the flexural strength. The aim of this investigation is to study the change in ductility of structural concrete flexural members during their exposure to limited cycles of repeated loading. Twenty full-scale beam specimens have been fabricated in to two identical groups; each group consisted of ten specimens. The first group was tested under monotonic static loading to failure and regarded as control beams, while the specimens of the second group were subjected to ten cycles of repeated loading with constant load interval, which ranged between 40% and 60% of ultimate load. S

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Publication Date
Thu Sep 15 2022
Journal Name
Bionatura
Submission and Phylogenetical of Local Isolated Trichophyton interdigitale of Iraqi Patients in NCBI
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Dermatophytes are species with slight genetic variation, and are yet several uncertainties about the differences among species. This study aims to isolate and diagnose the Trichophyton interdigitale by molecular technique and to reveal the phylogenetic distance and similarity of the Iraqi isolates to other isolates from the globe, in addition, to submit the obtained sequences to the NCBI database. This study included 86 with multiple lesions on different parts of the body. The results showed different variations within the ITS gene between the isolates. It was concluded that Trichophyton interdigitale in Iraqi isolates had two types of substitution variations (Transition and Transversion) different than global isolates. Moreover, it

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
The Chronic Effects of Salinity in the Biology of ?? Rotifers Brachionus calyciflorus Pallas
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The present study included the effect of chronic exposure for two concentrations of NaC? salt on the biology of fresh water zooplankton species Brachionus calyciflorus (from ^otifera). The concentrations 0.5 , 0.75%o were used for chronic exposure to investigate its effects on the life tables, range of the rate of expectation for further life and reproduction. The rotifer B. calyciflorus was sensitive to salinity and may tried to protect the species by increasing the size (2.22 ind./clutch lor control group and 2.9? for 0.5%o concentration) and number of clutches produced ?.1? clutch/female for control group and 2.9 ' ' ' for 0.75 %0 concentration) beside stimulation the animal to produce the first clutch of eggs earlier? ? small reduction

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Publication Date
Tue May 31 2022
Journal Name
International Journal Of Research In Social Sciences & Humanities
A Critical Discourse Analysis Study of Silence in Selected Texts of Virginia Woolf
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BN Rashid, Social Sciences, 2022

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Publication Date
Mon Nov 14 2022
Journal Name
Biomedicine
Molecular characterization of HBB gene mutations in beta-thalassemia patients of Southern Iraq
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Introduction and Aim: Beta-thalassemia is a serious inherited genetic disorder and an increasing health burden globally. Beta -thalassemia is caused by genetic globin abnormalities within the hemoglobin beta (HBB) gene. This study aimed to characterize the HBB gene mutations in beta -thalassemia among southern Iraqi patients. Materials and Methods: The study included 30 beta -thalassemia patients referred to the Thi-Qar Center for Genetic Diseases, Iraq and 15 control samples from a random group of apparently healthy individuals. Genomic DNA was isolated from blood sample collected from each individual. The DNA was amplified for specific regions of the HBB gene and the amplified products sequenced. The sequences generated were analysed for

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Publication Date
Thu Jan 06 2011
Journal Name
Arpn Journal Of Agricultural And Biological Science
EFFECT OF FEEDS CONTAINING DIFFERENT FATS ON CERTAIN CARCASS PARAMETERS OF JAPANESE QUAIL
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The aim of this study was to determine the effect of different dietary fat on carcass traits in Japanese quail (Coturnix coturnix japonica). A total of 168 7-week-old Japanese quail (48 males and 120 females) were used in this study. They were evenly distributed into 4 treatment groups, with 3 replicates per group containing 4 males and 10 females each. The birds were fed a basal diet with different fats (sunflower, flax, corn, and fish oils) at a 3% level for 13 weeks. On the last day of the experiment, 12 birds were randomly selected from each treatment group (6 males and 6 females) and slaughtered to determine carcass characteristics included in this study, which were carcass weight, dressing percentage with or without giblets, and the r

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Publication Date
Sun Dec 01 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Reflection of the application of the IFRSs on financial ratios and performance indicators
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The research aims to delve into the nature of international financial reporting standards and the unified accounting system adopted in the Iraqi environment and financial ratios in the theoretical side. In the practical aspect, the results of some financial ratios of Basrah Gas Company were compared with the adoption of the financial statements prepared on the basis of the consolidated accounting system with the prepared financial statements Based on the International Financial Reporting Standards (IFRS). The research has reached a number of conclusions, including a difference in the accounting rules and practices between IFRS and the consolidated accounting system in force in Iraq. The adoption of IFRS has led to a decrease in profitabi

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Publication Date
Wed Jun 01 2016
Journal Name
Journal Of The College Of Languages (jcl)
The tragedies of love and death in the tragedy of Federico Garcia Lorca
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Abstract:

    Federico Garcia Lorca is considered in european and american literary circles as revolutionary symbol of contemporary literature writer through close association with the concerns of his country and the world, and also through the violent propensity to freedom, emancipation and innovation. This personal multi-talent has a significant impact in the spanish literary movement, in particularly, and in world, in general. If Lorca has andalusia blood, is no stranger to contemporary arab man to read to him, and contemplates his experience analyst and literary critic. This research is serious study of this character. There is no doubt the reader will put in front of many facts about personali

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Publication Date
Wed May 01 2019
Journal Name
Proceedings Of International Structural Engineering And Construction
FLEXURAL DUCTILITY OF STRUCTURAL CONCRETE MEMBERS SUBJECTED TO LIMITED CYCLES OF REPEATED LOADING
...Show More Authors

For structural concrete members that may expose to serious earthquake, overload or accident impact, the design of ductility must be given the same importance as the flexural strength. The aim of this investigation is to study the change in ductility of structural concrete flexural members during their exposure to limited cycles of repeated loading. Twenty full-scale beam specimens have been fabricated in to two identical groups; each group consisted of ten specimens. The first group was tested under monotonic static loading to failure and regarded as control beams, while the specimens of the second group were subjected to ten cycles of repeated loading with constant load interval, which ranged between 40% and 60% of ultimate load. S

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