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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
Sun Jul 28 2019
Journal Name
Open Access Macedonian Journal Of Medical Sciences
Value of Combination of Standard Axial and Thin-Section Coronal Diffusion-weighted Imaging in Diagnosis of Acute Brainstem Infarction
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AIM: To determine the value of the combination of thin-section 3 mm ‎coronal and standard ‎axial DWI and their impact in facilitating the diagnosis of ‎‎acute brainstem infarction. METHODS: A cross-sectional study conducted from the 1st of April 2017 to the end of February 2018 on 100 consecutive patients (66% were male, and 34% were female) with isolated acute ischemic infarction in the ‎brainstem. The abnormal MRI findings concerning the ischemic lesions were interpreted on standard axial 5 mm and thin-section coronal 3mm DWI. RESULTS: The mean age of the studied group was 69.2 ± 4.3 for male and 72.3 ± 2.5 years. The standard axial DWI can diagnose 20%, 6.7% and 6.7% of the infarctions in midbrain, pons an

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Publication Date
Tue Jan 01 2019
Journal Name
International Journal Of Civil Engineering And Technology
PREDICTION OF BEARING CAPACITY, ANGLE OF INTERNAL FRICTION, COHESION, AND PLASTICITY INDEX USING ANN (CASE STUDY OF BAGHDAD, IRAQ).
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In the last few years, the use of artificial neural network analysis has increased, particularly, in geotechnical engineering problems and has demonstrated some success. In this research, artificial neural network analysis endeavors to predict the relationship between physical and mechanical properties of Baghdad soil by making different trials between standard penetration test, liquid limit, plastic limit, plasticity index, cohesion, angle of internal friction, and bearing capacity. The analysis revealed that the changes in natural water content and plastic limit have a great effect on the cohesion of soil and the angle of internal friction, respectively. . On the other hand, the liquid limit has a great impact on the bearing capacity and

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Publication Date
Sun Sep 06 2015
Journal Name
Baghdad Science Journal
Evaluation of the level of Some Heavy Metals in Tobacco of Domestic and Imported Cigarette Brands Used in Iraq
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Smoking-related diseases can be attributed to the inhalation of many different toxins, including heavy metals, which have a host of harmful health effects. The primary objective of this study was to determine whether local and imported cigarette brands used in Iraq , have they elevated levels of metals or not .Three metals Lead (Pb) , Cadmium (Cd) and Chromium(Cr) were determined in tobacco of seventeen brands of imported cigarettes commonly available in Iraq and three Iraqi domestic cigarettes , which were randomly taken from retail market in Baghdad by using flame atomic absorption spectrometry. The produced data of imported and local cigarette brands were discussed and compared together and with studies from elsewhere .The result

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Publication Date
Sat Jul 23 2016
Journal Name
Association Of Genetic And Environmental Resources Conservation (
Effect of cold and hot aqueous extract of garlic on the reproductive performance of immature male mice until puberty
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This study was investigated the role of garlic extracts on the reproductive functions, via the development of immature male mice (25 days old) un l puberty. Immature male mice were divided into 3 groups (n=25). Group 1 "control" was daily administrated with tap water. Group 2 was daily administrated with cold aqueous garlic extract. Group 3 was daily administrated with hot aqueous garlic extract. Each group was randomly consisted of 5 subgroups (n=5/ subgroup) and administrated for different periods i.e, 1, 2, 3, 4 and 5 weeks respectively. Animals were scarified after 24 h from last treatment. Our findings elucidated that, cold and hot aqueous garlic extracts, when administrated at 25 days old (Immature period) have different impact dep

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Publication Date
Wed Oct 01 2014
Journal Name
Al–bahith Al–a'alami
Study of the patterns of media frames used in the production of Arabic spring breaks in Al Arabiya channel
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production of the spot in the news channels - a study of patterns of spot media used in the production of spring breaks Arab Al-Arabiya

 The spacers news in Arabic, one of the messages that seek channel output are fit and policy on the one hand and meet the needs of viewers for information intensive and image influential to find out the latest developments on the Arab arena, especially the Syrian revolution on the other and thus The viewer for the type of coverage the stomach through a newsletter about the event on the one hand to keep following up on her and eager to watch the other hand

 

 

And sou

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Publication Date
Tue Mar 15 2022
Journal Name
Al-academy
The semiotics of the visual image of women in the discourse of empowerment, Saudi Arabia Kingdom as a model
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We studied, in this paper, the semiotics of the visual image of women in the discourse of empowerment, through three models of advertising images expressing the particularities of the Saudi Arabian environment.

We aim to know how the mark operates and how it is interpreted, as a semantic process in which the meaning ranges from description to interpretation, and we studied two hypotheses:

-The advertising image is a structure in which the mark corresponds to the reality and the discourse to the context.

-The significance is not found in the visual sign or in the textual sign of the advertising image, but in the creative event that opens up to the social, cultural, and psychological context, and creates a field of dia

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Publication Date
Mon Mar 01 2010
Journal Name
Journal Of Economics And Administrative Sciences
The economic feasibility of substituting different residues replaces part of the barley In the fattening of the Arabian lambs
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This experiment was carried out at the Grdarash field belongs to the Agricultural researches directorate/general Agriculture directorate-Erbil in September (2007)، 27 Arabic lambs aged (5-6 months) With average initial weight (39.178 Kg/lamb) were used. Lambs were divided in to (3) groups (9 lambs/group). Control group was fed on (85% barely، 10% bran and 5% straw)، and second and third groups were fed on various by-product in replacement with barely in loss and block shape respectively.

The total gain of three groups were (392708.32، 634826.52 & 445613.72 ID resp

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Publication Date
Thu Sep 01 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of alkaline phosphatase, salivary flow rate and salivary potential of hydrogen in relation to severity of chronic periodontitis
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Publication Date
Sun Jul 01 2012
Journal Name
Journal Of Engineering
Preparation of Design Charts for Estimation of the Length of an Upstream Impervious Blanket in a Homogenous Earth Dam
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Publication Date
Wed Jul 01 2020
Journal Name
Proceedings Of The Institution Of Mechanical Engineers, Part H: Journal Of Engineering In Medicine
Comparison study of classification methods of intramuscular electromyography data for non-human primate model of traumatic spinal cord injury
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Traumatic spinal cord injury is a serious neurological disorder. Patients experience a plethora of symptoms that can be attributed to the nerve fiber tracts that are compromised. This includes limb weakness, sensory impairment, and truncal instability, as well as a variety of autonomic abnormalities. This article will discuss how machine learning classification can be used to characterize the initial impairment and subsequent recovery of electromyography signals in an non-human primate model of traumatic spinal cord injury. The ultimate objective is to identify potential treatments for traumatic spinal cord injury. This work focuses specifically on finding a suitable classifier that differentiates between two distinct experimental

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