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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
Fri Jun 01 2012
Journal Name
European Journal Of Scientific Research
Occurrence of Cryptosporidium spp among people live in north of Baghdad
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In this study 737 stool specimens were collected from people attending some primary health care centres and hospitals in North of Baghdad, during the period from beginning of April 2009 till the end of March 2010. Different factors were examined to be related with the prevalence of Cryptosporidiosis which were (number of family member, travelling history, source of drinking water and domestic animal present). Significant relations (p≤0.05) were observed between infection rate and the following factor: -Number of family member: The high percentage of Cryptosporidium spp positive cases were seen in families composed of (15-19) and (more than 20) individual which were 28.32% and 16.37% respectively when compared with other family clusters -T

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Publication Date
Fri Aug 31 2012
Journal Name
Al-khwarizmi Engineering Journal
Study of Mechanical Properties of (Al-Cu-Mg) Alloy Matrix Composite
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The present research had dealt with preparing  bars  with the length of about  (13 cm) and  adiametar  of  (1.5 cm) of composite materials with metal  matrix  represented by (Al-Cu-Mg) alloy cast enforced by (ZrO2) particles with chosen weight  percentages (1.5, 2.5 ,3.5, 5.5 %). The base  cast and the composite  materials were prepared by casting method by uses vortex  Technique inorder to  fix up (ZrO2) particles in homogeneous way on  the  base cast. In addition to  that, two main groups of composite materials were prepared depending on the particles size of (ZrO2) , respectively.       &n

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Publication Date
Mon Feb 04 2019
Journal Name
Journal Of The College Of Education For Women
The Study of Traffic on The Roads The Governorate Of Karbala
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The study of traffic on the roads the governorate of Karbala, Where is the study of traffic on the roads measure is necessary to determine the extent of the road and highlighting the importance of its role in the transfer of individuals from original to destination as well as the importance of the region that attracted its movement. This research aims to analyze the traffic in the governorate of Karbala through the study and analysis of surveys of traffic that were made in the governorate. Based on this analysis, it has been reached to identify volumes of the traffic and its density and how the roads are efficient and accommodating these volumes, the results of the traffic survey of the studied roads in the area of the study have shown t

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Publication Date
Sun Jun 01 2014
Journal Name
Baghdad Science Journal
Distribution of Some Heavy Metals in Tigris River middle of Iraq
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This study was conducted from February 2010 to December 2010. Water Samples were collected every two months in three stations in Baghdad city. The study involved the assessment of concentrations of some heavy metals such as: Chromium, Cadmium, Copper, Iron, Lead, Manganese, Nickel and Zinc. the values of chromium were undetected for the entire of the study, while the rest of the heavy metal were ranged between 0.001 -0.438 mg / l, ND -0.077 mg / L, ND -0.778 mg / l, 0.36 - 0.011 mg / l, 0.011-0 .08mg/ l, ND - 0.1985 mg / l, ND -0.0416 mg / l, respectively. The results showed that the concentrations of heavy metals were fluctuated during the study period, except Lead which have high concentrations and exceeded the permit limits in all statio

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Publication Date
Sun Mar 13 2011
Journal Name
Baghdad Science Journal
Curing of mice skin infections using ethanol flower extract of chamomile
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This experiment was conducted in order to estimate azulene and apigenin in chamomile flowers. Ethanol extracts were examined singly or in combination with some drugs in their biological activity against some pathogens causing skin infection. Ethanol extract was applied at a concentration of 40 mg/ml for the treatment of induced skin infection of mice. Among the topicals used, Claforan was found the most effective on microorganisms causing skin diseases; ethanol extract was more effective than the drug Candimazole solution 1%. HPLC was used for the determination of azulene and apigenin active compounds of chamomile plant.

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Publication Date
Sun Aug 30 2020
Journal Name
Journal Of Economics And Administrative Sciences
The Influence of Emotional Intelligence in promoting the Empowerment of Employees
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The subject of the research seeks to indicate the level of influence of emotional intelligence in the empowerment of workers in the Ministry of Industry and Minerals General Company for Food Products. The research problem is illustrated by knowing all of the following:

  • The level of the relationship between emotional intelligence in promoting the empowerment of employees of the Ministry of Industry and Minerals.
  • The impact of emotional intelligence on the empowerment of workers in the ministry.
  • Recognize the interest of the management of the Ministry of Industry and Minerals in emotional intelligence and the

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Publication Date
Sun Apr 30 2017
Journal Name
Journal Of Engineering
The Effect of Fin Design on Thermal Performance of Heat Sink
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      An experimental and computational study is conducted to analyze the thermal performance of heat sinks and to pick up more profound information in this imperative field in the electronic cooling. One important approach to improve the heat transfer on the air-side of the heat exchanger is to adjust the fin geometry. Experiments are conducted to explore the impact of the changing of diverse operational and geometrical parameters on the heat sink thermal
performance. The working fluid used is air. Operational parameters includes: air Reynolds number (from 23597 to 3848.9) and heat flux (from 3954 to 38357 W/m
2 ). Conformational parameters includes: change the direction of air flow and the area of conduct

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Publication Date
Mon Dec 05 2022
Journal Name
Baghdad Science Journal
Cluster Analysis of Biochemical Markers as Predictor of COVID-19 Severity
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Numerous blood biomarkers are altered in COVID-19 patients; however, no early biochemical markers are currently being used in clinical practice to predict COVID-19 severity. COVID-19, the most recent pandemic, is caused by the SRS-CoV-2 coronavirus.  The study was aimed to identify patient groups with a high and low risk of developing COVID-19 using a cluster analysis of several biomarkers. 137 women with confirmed SARS CoV-2 RNA testing were collected and analyzed for biochemical profiles. Two-dimensional automated hierarchy clustering of all biomarkers was applied, and patients were sorted into classes. Biochemistry marker variations (Ferritin, lactate dehydrogenase LDH, D-dimer, and C- reactive protein CRP) have split COVID-19 patien

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Publication Date
Sat Aug 01 2015
Journal Name
Journal Of Engineering
Reducing of Manufacturing Lead Time by Implementation of Lean Manufacturing Principles
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Many organizations today are  interesting to implementing lean manufacturing principles  that should enable them to eliminating the wastes to reducing a  manufacturing lead time.  This paper concentrates on  increasing  the competitive level of the company in globalization markets and improving of the productivity by reducing the manufacturing lead time. This will be by using the main tool of lean manufacturing which is value stream mapping (VSM) to identifying all the activities of manufacturing process (value and non-value added activities) to reducing elimination of wastes (non-value added activities) by converting a manufacturing system to pull instead of push by applying some of pull system strategies a

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Publication Date
Wed May 24 2023
Journal Name
College Of Islamic Sciences
Metaphor in the interpretation of the long sea of Ibn Ajiba
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Scientists have delved too much into reality and metaphor, and perhaps a topic of Arabic rhetoric has not received the attention and care of scholars as much as the topic of truth and metaphor. The metaphor opens wide horizons of expression in front of the writer so that he has several means by which he can express the one experience, so his imagination takes off depicting the intelligible as tangible, the seen as audible, and the audible as seen. That image presented by the creative writer.
The first thing to note is that the emergence of metaphor as a rhetorical term was at the hands of the Mu'tazila. Muslims differed about the issue of metaphor in the Holy Qur’an, and the beginning of the dispute was about the verses in which the

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