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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 Jun 01 2021
Journal Name
Iop Conference Series: Materials Science And Engineering
Hydraulic characteristics of the lower part of Diyala River
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Abstract<p>A one-dimensional hydraulic model was conducted to simulate the flow in Diyala River. The research aims to study the flow capacity along Diyala River and especially concerning on reach of the river within Baqubah City during flood seasons by using HEC-RAS, 5.07 software. Moreover, specifying the hydraulic problems and then the necessary treatments to overcome them were suggested. A 190 km length of the reach of Diyala River was included in this study, starts from Diyala submerged weir to the confluence of Diyala-Tigris River south of Baghdad City. Good agreement resulted between the measured and the simulation results with a determination coefficient (R2) value of 0.84 with Manning Co</p> ... Show More
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Publication Date
Sat Jan 01 2022
Journal Name
Journal Of Advanced Pharmacy Education And Research
Formulation and evaluation of mucoadhesive buccal tablet of Anastrozole
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Publication Date
Tue Jul 17 2012
Journal Name
مجلة مركز بحوث التقنيات الاحيائية
Effecienty of Immobilization technique of Bacillus Sublilis Asperginase producer
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Abstract Twenty Bacillus isolated were obtained from different sample food and water. Bacillus B1 isolated was the highest asparaginase producer, it was identified as a strain of B. subtilis. The highest production of asparaginase was observed when mineral salt medium containing 0.3% asparagen, pH 8 and incubated at 40°c for 24 hrs. B. subtilis B1 cells were immobilized by entrapment methods (calcium alginate and agar), and by adsorption on solid surface such as sawdust and cotton. The result showed that the immobilized cells by adsorption on sawdust was the best, the immobilized cell retained 88% of asparginase activity after 48h while free cell retained 65%. Cells immobilized by adsorption on sawdust was incubated at different temperatu

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Publication Date
Tue Dec 01 2015
Journal Name
Journal Of Engineering
Operation of the Iraqi Part of Al-Huweizah Marsh
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Al-Huweizah Marsh is considered as the largest in Iraq. This research aims to maintain thesustainability of Al-Huweizah Marsh under all circumstances and within the limits of the
available natural resources from the Iraqi side and the absence of feeding from the Iranian sidedue to the recent Iranian separation dike along the international boundaries within the marsh.
Twelve scenarios have been suggested as a first step to restore the whole marsh. But the
uncontrolled Iranian feeders and exiguity of their discharges recently, it was necessary to studyonly the northern part of the marsh as an alternative case to ensure reasonable amounts of waterfor the purpose of maintaining and restore the marsh. Hydrological routing model was

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Publication Date
Sun Jun 12 2011
Journal Name
Baghdad Science Journal
Measurement of Uranium Concentration in Soil of Middle of Iraq using CR ?V 39 Track Detector
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The aim of this research is to determine the uranium concentration in soil and water samples taken from different locations from the middle and south of Iraq using fission fragments track registration. Twelve samples of soil and water were taken from middle and South of Iraq. The nuclear reaction used as a source of nuclear fission fragments is U-235 (n.f) obtained by bombardment U-235with thermal neutrons from (Am-Be) neutron source with flux (5X103 n.cm-2.s-1). The concentration values were calculated by a comparison with standard samples recommended by IAEA.The results of the measurements show that the uranium concentration in soil samples were in Thekar (16.38 ppm), AL-Basra (16.1ppm) and (0.78 ppm) in Baghdad, from the results

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Publication Date
Thu Jun 30 2011
Journal Name
Al-kindy College Medical Journal
Effect of war on treatment of pulmonary tuberculosis, and evaluation of Directly-observed therapy in Baghdad
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Background: Directly observed therapy-short course (DOTS) had been adopted by World Health Organization (WHO) as hopeful strategy for treatment of tuberculosis (TB) since early nineties. Iraqi health authorities started DOTS implementation since 2001 in Baghdad. Coverage expanded gradually till 100% in 2004. War and unstable security condition hit Iraq since March 2003. Objective: The objective of this study was To evaluate the DOTS implementation program in Baghdad in different periods including 2 unstable periods for proper assessment of war and instability on treatment of TB. Patients and methods: This study had been conducted in Baghdad during four different periods (before and during 2003 war, after war; without and with DOTS). Dire

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Publication Date
Tue Mar 30 2010
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
The Effect of Operating Conditions of Urea Dewaxing on the Pour Point of Light Lubricating Oil
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An investigation was conducted for dewaxing of lubricating oil fraction by urea to reduce the pour point.In this study mixture of 45 % methyl ethyl ketone (MEK) and 55 % toluene was used as a solvent. The studied variables are mixing time (10-70 min), solvent to oil volume ratio (0.5:1- 2:1), urea to wax weight ratio (2- 6) and constant mixing speed 1500 rpm. By analysis of the experimental results, the best operating conditions achieved are mixing time 40 min, solvent/oil 2:1 volume ratio, and urea/wax 4:1 weight ratio. At these conditions the pour point of the lubricating oil decreases from 24 ° C to -13 °C.

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Publication Date
Sun Feb 01 2015
Journal Name
Journal Of Engineering
Effect of Saturation of Sandy Soil on the Displacement Amplitude of Soil Foundation System under Vibration
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In this study, the response and behavior of machine foundations resting on dry and saturated sand was investigated experimentally. A physical model was manufactured to simulate steady state harmonic load at different operating frequencies. The effect of relative density, depth of embedment, foundation area as well as the imposed harmonic load was investigated. It was found that the amplitude of displacement of the foundation increases with increasing the amplitude of dynamic force and operating frequency meanwhile it decreases with increasing the relative density of sand, degree of saturation, depth of embedment and contact area of footing. The maximum displacement was noticed at 33.34 to 41.67 Hz. The maximum displacement amplitude respons

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Publication Date
Sat May 30 2020
Journal Name
Neuroquantology Journal
The Effect of Re-Use of Lossy JPEG Compression Algorithm on the Quality of Satellite Image
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In this study, an analysis of re-using the JPEG lossy algorithm on the quality of satellite imagery is presented. The standard JPEG compression algorithm is adopted and applied using Irfan view program, the rang of JPEG quality that used is 50-100.Depending on the calculated satellite image quality variation, the maximum number of the re-use of the JPEG lossy algorithm adopted in this study is 50 times. The image quality degradation to the JPEG quality factor and the number of re-use of the JPEG algorithm to store the satellite image is analyzed.

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Publication Date
Sat Dec 01 2018
Journal Name
Al-khwarizmi Engineering Journal
The Influence of Alkaline Treatment of Recycled Natural Materials on the Properties of Epoxy Resin Composites
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Natural fibers and particles reinforced composites are being broadly used due to their bio and specific properties such as low density and easy to machine and production with low cost. In this work, water absorption and mechanical properties such as tensile strength, flexural strength and impact strength of recycled jute fibers reinforced epoxy resin were enhanced by treating these fibers with alkaline solution. The recycled jute fibers were treated with different concentration of (NaOH) solution at (25 0C) for a period of (24) hours. From the obtained results, it was found that all these properties are improved when fibers treated with (7.5wt% NaOH) related to untreated fibers. Conversely, the mentioned properties of composit

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