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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
Tue Dec 01 2015
Journal Name
Journal Of Engineering
Effect of Metakaolin on the geotechnical properties of Expansive Soil
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Expansive soil spreads in Iraq and some countries of the world. But there are many problems can be occurred to the structures that built on, so we must study the characteristics of these soils due to the  problems that may be caused to these structures which built on these kinds of soil and then study the methods of treatment. The present study focuses on improving  the geotechnical properties of expansive soils by treating it Metakaolin(M). Metakaolin (M) has never been used before as an improvement material  for stabilizing the expansive soil . Metakaolin  is a pozzolanic material. It’s obtained by calcination of kaolinite clay at temperatures from 700°C to 800°C. Kaolin chemical composition is

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Publication Date
Thu Jun 30 2022
Journal Name
Iraqi Geological Journal
Assessment of the Contamination of Baghdad Soils with Lead Element
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The present study aims to study the content and spatial distribution of lead (Pb) contamination in the soils of some Baghdad cities (Middle of Iraq). Twenty soil samples were randomly collected from different land-use in the studied area at a depth between 5 to 30 cm. Ten samples are collected from Al-Rissafa side areas (Adhamiya, Al-Wazeeria (Battery Manufacturer), Shikh Omer, Ziyouna, Karada, Shaab, Sadr city, Al-Za’franiya, Al-Dora expressway, and Alselikh ) and other ten samples are collected from Al-Krakh side areas Al-Dora, Al-Masafi junction, Al-Dora, Sayidia, Al-Salam university college, Al-Bayaa (Industrial District), Jehad, Amirya, Abu Ghraib, Al-hurriya, and Kadhimiya. The soil samples have been analyzed for the lead (P

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Publication Date
Tue Jul 01 2003
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
THE ABDOMINAL NERVE GANGLIA OF SOME CARABIDAE (COLEOPTERA) OF IRAQ
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The abdominal nerve cord of some species of Iraq Carabids has been studied to evaluate
the variation in the number of the abdominal ganglia among the species and to find out
relation of these variations with the classical taxonomy of the family Carabidae into tribes.

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Publication Date
Thu Sep 15 2022
Journal Name
Al-academy
Attributes of the figure in the work of Afifa Aleiby
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The experiments and artistic performances in contemporary Iraqi painting varied between objective simulation and experimentation in other invisible worlds through metaphor and employment to express the latent implications between the human relationship with the tangible and the intangible. The research problem contained the answer to the following questions to understand the formal features in Afifa Laibi's drawings: What are the formal features of Afifa Laibi's drawings and what are the intellectual transformations that she embodied in presenting her subjective subjects? Did the Iraqi and global environmental changes and influences contribute to the forms of Afifa Laibi? The importance of the research also lies in the study of one of th

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Publication Date
Fri Nov 09 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Assessment of Severity of Anemia Among Children Under 5 Years
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Objective(s): The aim of this study was to assess the severity of anemia among children under 5 years and to find
out relationship between severity of anemia in children with socio-demographic variables such as: child gender,
age, supplement diet, hookworm, pica, parent's education level, father's and mother's occupation, and family
monthly income with severity of anemia
Methodology: A descriptive cross sectional study was conducted at the primary health care centers in Alsadr city
for the period of 1
st July 2011 to the 1st November 2011.Non probability (purposive) sample of (630) children who
aged under 5 years and who attended to primary health care centers of Alsadr city. The data were collected
through using

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Publication Date
Tue Jun 21 2022
Journal Name
Journal Of Planner And Development
Knowing the shape of the physical identity of the city
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This  research deals with the form of the physical identity which is concerned with the features and characteristics that distinguish the shape of the city from other existing cities and reveal its similarity with the self (itself) and objective difference with others.  Accordingly, these features must be sophisticated and variable resulting the shape of the city, while preserving the continuity of time, and eventually leads to the emergence of the whole shape. Physical identity is conceptually equivalent with the terms "personality" and "sense of place".  The research determined the criteria for evaluating the physical identity as follows:              

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Publication Date
Thu Jun 29 2017
Journal Name
College Of Islamic Sciences
The prohibition of cheating in the Sunnah of the Prophet
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In The Name of Allah Most Gracious Most Merciful

Cheating is one of the forbidden actions and reprehensible morals that are forbidden by Islamic law, because it involves an assault on rights, whether they are the rights of God Almighty or the rights of God.

people, or self-rights, and because it involves harming others.

Since the Sunnah of the Prophet is the second source of Islamic law, many of the noble hadiths of the Prophet forbid and prohibit cheating.

This study sheds light on it.

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Publication Date
Fri Jun 30 2023
Journal Name
College Of Islamic Sciences
The Role Of Atheism In The Demolition Of Societal Security
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The enemies of religion are still following the approach of undermining the Islamic faith in various ways through the diversity of methods of smear campaigns by raising suspicions to obliterate the Islamic identity and threaten security and stability of social life under the Islamic religion in Islamic societies, as we find that they have employed the doctrine of atheistic thought in order to distance people from the path of truth, distort the features of religion, destabilize psychological security and family stability, and thus destroy societal security by questioning the tolerant faith at times, and by raising suspicions at other times.

Hence, this research came to review the legal duty that requires Islamic scholars to protec

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Publication Date
Wed Mar 11 2020
Journal Name
Periodicals Of Engineering And Natural Sciences
Applied multivariate analysis of variance in experiment of randomized design
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The general aim of an experimental design in this paper was to estimate the different treatments effects on the responses by statistical methods. The estimates must be averting biases and the random errors minimized as much as possible. We used multivariate analysis of variance (MANOVA) to analyze design of experiments for several responses. In this paper, we provided three fertilizers (mineral, humic, micro-elements) applied on Yellow Maize experiment. This experiment was conducted by completely randomized design (CRD). We tested four responses (Chlorophyll in paper, total ton / ha, paper area / cm2 and plant height / cm) together to find significant test between them. The partial correlations are between Chlorophyll in paper and total ton

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Publication Date
Sat Sep 01 2018
Journal Name
Journal Of Pharmaceutical Sciences And Research
Preparation and characterization of oro-dispersible tablets of bromhexine hydrochloride
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