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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
Mon May 11 2020
Journal Name
Baghdad Science Journal
New Concepts of Fuzzy Local Function: Types of fuzzy local function
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The main idea of this paper is to define other types of a fuzzy local function and study the advantages and differences between them in addition to discussing some definitions of finding new fuzzy topologies. Also in this research, a new type of fuzzy closure has been defined, where the relation between the new type and different types of fuzzy local function has been studied

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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
Sun Sep 01 2024
Journal Name
Gazi University Journal Of Science
Effect of Natural Bitumen on the Performance of Hot Asphalt Mixture‏
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For over a century, the global consumption of asphalt binder in asphalt mixture production has been substantial. In the Heet region (west of Iraq), two distinct forms of natural asphalt (NA) deposits exist: rock asphalt and sulfur spring asphalt. This study focused on using NA sourced from sulfur springs. The aim was to investigate the potential of incorporating NA into local asphalt mixtures. To achieve this, NA was heated to 163°C for varying durations. After heat treatment, laboratory tests were conducted on NA. The findings suggest that by heating NA for 20 hours, it conforms to Iraqi specifications in terms of physical properties. Furthermore, compared to conventional petroleum asphalt, treated NA showed greater

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Publication Date
Sat Jul 28 2018
Journal Name
Journal Of Engineering
Effectiveness of Meso-Scale Approach in Modeling of Plain Concrete Beam
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The main aim of this research paper is investigating the effectiveness and validity of Meso-Scale Approach (MSA) as a modern technique for the modeling of plain concrete beams. Simply supported plain concrete beam was subjected to two-point loading to detect the response in flexural. Experimentally, a concrete mix was designed and prepared to produce three similar standard concrete prisms for flexural testing. The coarse aggregate used in this mix was crushed aggregate. Numerical Finite Element Analysis (FEA) was conducted on the same concrete beam using the meso-scale modeling. The numerical model was constructed to be a bi-phasic material consisting of cement mortar and coarse aggregate. The interface between the two c

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Publication Date
Fri Jul 01 2022
Journal Name
Journal Of Engineering
Influence of Stone Powder on the Mechanical Properties of Clayey Soil
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In this experimental study, the use of stone powder as a stabilizer to the clayey soil studied. Tests of Atterberg limits, compaction, fall cone (FCT), Laboratory vane shear (LVT), and expansion index (EI) were carried out on soil-stone powder mixtures with fixed ratios of stone powder (0%, 5%, 10%, 15%, and 20%) by the dry weight. Results indicated that the undrained shear strength obtained from FCT and LVT increased at all the admixture ratios, and the expansion index reduced with the increase of the stone powder.

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Publication Date
Mon Aug 01 2011
Journal Name
Journal Of Engineering
IMPLEMENTATION OF ROOT FINDING ALGORITHM OF MINIMUM PHASE FILTER USING VHDL
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Root-finding is an oldest classical problem, which is still an important research topic, due to its impact on computational algebra and geometry. In communications systems, when the impulse response of the channel is minimum phase the state of equalization algorithm is reduced and the spectral efficiency will improved. To make the channel impulse response minimum phase the prefilter which is called minimum phase filter is used, the adaptation of the minimum phase filter need root finding algorithm. In this paper, the VHDL implementation of the root finding algorithm introduced by Clark and Hau is introduced.
VHDL program is used in the work, to find the roots of two channels and make them minimum phase, the obtained output results are

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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
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
Fri May 31 2019
Journal Name
Journal Of Engineering
Geological Model of the Tight Reservoir (Sadi Reservoir-Southern of Iraq)
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A3D geological model was constructed for Al-Sadi reservoir/ Halfaya Oil Field which is discovered in 1976 and located 35 km from Amara city, southern of Iraq towards the Iraqi/ Iranian borders.

Petrel 2014 was used to build the geological model. This model was created depending on the available information about the reservoir under study such as 2D seismic map, top and bottom of wells, geological data & well log analysis (CPI). However, the reservoir was sub-divided into 132x117x80 grid cells in the X, Y&Z directions respectively, in order to well represent the entire Al-Sadi reservoir.

Well log interpretation (CPI) and core data for the existing 6 wells were the basis of the petrophysical model (

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Publication Date
Tue Sep 01 2020
Journal Name
Baghdad Science Journal
Identification of Acinetobacter baumannii and Determination of MDR and XDR Strains
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The current study focuses on the bacterium Acinetobacter baumannii due to its importance as a nosocomial infections source in addition to its increased resistance against antibiotics. Different clinical and hospital environment samples were collected, and cultured on A. baumannii selective media: Leed Acinetobacter agar and Herellea agar. A. baumannii have been identified by traditional methods, followed by confirmation using molecular identification to detect blaoxa-51 like gene which is considered a diagnostic gene since it is present in genome of all A. baumannii strains. The result was, nineteen bacterial isolates of A.baumannii were obtained, from twenty-seven suspected isolate

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