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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 01 2017
Journal Name
International Journal Of Applied Pharmaceutics
DEVELOPMENT AND PHYSICAL CHARACTERIZATION OF A PERIODONTAL BIOADHESIVE GEL OF GATIFLOXACIN
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Objective: The aim of this study was to develop a bioadhesive gel of gatifloxacin for the treatment of periodontal diseases.Methods: Periodontal gels of gatifloxacin were prepared using different hydrophilic polymers such as carbopol 940 (CP 940), carboxymethyl cellulose (CMC) and hydroxypropylmethyl cellulose (HPMC) in varied concentrations, either alone or as a combination. The prepared gels were evaluated for their physical appearance, pH, drug content, viscosity, bioadhesiveness and in vitro drug release profile. The influence of the type and the concentration of polymer on the drug release as well as on viscosity and mucoadhesiveness of prepared gels were investigated.Results: The prepared gels showed acceptable physical proper

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Publication Date
Mon Jul 19 2021
Journal Name
Surgical Neurology International
Efficacy of Gamma Knife radiosurgery in the management of pituitary prolactinoma
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Background:

Gamma Knife radiosurgery (GKR) has been widely used in the management of a variety of intracranial tumors, including pituitary adenomas. Pituitary prolactinoma (Prs) is one of the most common types of these adenomas.

Methods:

This prospective study included 50 patients with pituitary Prs over a period from June 2017 to June 2018 at the Neurosciences Hospital, Baghdad/Iraq. The GKR procedure was performed using the Leksell Gamma Knife® Perfexion™, 192 beams of Cobalt 60 radiation were delivered through the intact skull to the pituitary Prs.

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Publication Date
Tue Dec 16 2008
Journal Name
Journal Of Planner And Development
The system of urban stability in the Kurdistan Region of Iraq
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The developing countries can be distinguished by spatial disparities and by this a wide gap between urban and rural settlements were produced as well as the appearance of primate cities. The effect of spatial development as a dynamic and continuous process can be perceived in the state of population distribution inside settlements inter and intra regions as well as the hierarchy of urban settlements according to time series. The research proved that the improvement judgment of the structure of the urban system using Gene factor is not accurate because it cannot be accounted for the internal components of the system which make a contrariety between the whole judgment (country) and partial components (Provinces including Sulaimaniy

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Publication Date
Sat Jan 14 2017
Journal Name
Chemical And Biomolecular Engineering
Influence of Nano Additives on Unconfined Compressive Strength of Asphaltic Soil
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Collapsible behaviour of soil is considered as one of the major problems in the stability of roadway embankment, the lack of cohesion between soil particles and its sensitivity to the change of moisture content are reasons for such problem. Creation of such cohesion may be achieved by implementation of liquid asphalt and introduction of Nano additives. In this work, silica fumes, fly ash and lime have been implemented with the aid of asphalt emulsion to improve the unconfined compressive strength of the collapsible soil. Specimens of 38 mm in diameter and 76 mm height have been prepared with various percentages of each type of Nano additive and fluid content. Specimens were subjected to unconfined compressive strength determination at dry a

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Publication Date
Mon Sep 30 2019
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Development of East Baghdad Oil Field By Clusters of Horizontal Wells
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There are varieties of reasons lead for drilling horizontal wells rather than verticals. Increasing the recovery of oil, especially from thin or tight reservoir permeability is the most important parameter.

East Baghdad oil field considered as a giant field with approximately more than 1billion barrel of a proved reserves accompanying recently to low production rate problems in many of the existing wells.

   It is important to say that presence of of  horizontal wells in East Baghdad field especially by converting some of already drilled wells by re-entry drilling horizontal sections may provide one of best solutions for the primary development stage in East Baghdad field which may be followed by drilling n

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Publication Date
Tue May 16 2023
Journal Name
Journal Of Engineering
Improvement of Resistance Spot Welding by Surfaces Treatment of AA1050 Sheets
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Resistance spot welding (RSW) aluminum alloys has a major problem of inconsistent quality from weld to weld, because of the problems of the non-uniform oxide layer. The high resistivity of the oxide causes strong heat released which influence significantly on the electrode lifetime and the weld quality. Much effort has been devoted experimentally to the study of the sheet surface characteristics for as-received sheet and surface pretreatment sheet by pickling in NaOH and glassblasted with three thicknesses (0.6, 1.0, and 1.5 mm) of AA1050. Three different welding process parameters energy setup as a low, medium, and high were carried. Tensile-shear strength tests were performed to indicate the weld quality. Moreover, microhardness tests,

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Publication Date
Sun Feb 03 2019
Journal Name
Iraqi Journal Of Physics
A study of the characterization of CdS/PMMA nanocomposite thin film
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Nanocomposites of polymer material based on CdS as filler
material and poly methyl methacrylate (PMMA) as host matrix have
been fabricated by chemical spray pyrolysis method on glass
substrate. CdS particles synthesized by co-precipitation route using
cadimium chloride and thioacetamide as starting materials and
ammonium hydroxide as precipitating agent. The structure is
examined by X-ray diffraction (XRD), the resultant film has
amorphous structure. The optical energy gap is found to be (4.5,
4.06) eV before and after CdS addition, respectively. Electrical
activation energy for CdS/PMMA has two regions with values of
0.079 and 0.433 eV.

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Publication Date
Mon Oct 01 2018
Journal Name
Plant Archives
A comparative anatomical study of three types of gymnospermplantscycasrevoluta,thujaoreintalisand cupressussemperviens
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Scopus
Publication Date
Thu Jul 01 1999
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
Hymenopterous parasites of cockroaches in Iraq with description of new species
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An attempt was made to determine the insect parasites of cockroaches in Iraq. As a result of this survey three species of Hymenoptera representing two separate families, which have been reared from ootheca of cockroaches were recovered. These were: Evania dimidiata Fabricius, Evania appendigaster (Linnaeus) (Evaniidae) and Anastatus longicornis sp. n. (Eupelmidae) which described here as a new species from Iraq.

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Publication Date
Tue Jan 01 2019
Journal Name
Lambert
The concept of Evil in J.R.R.Tolkien Novel Lord of the Rings
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Evil pervades the narrative scene in Tolkien. Hence; his major themes in The Lord of the Rings are shown to be the Evil Nature of Power, the Tyranny of Technology and War as a Destructive Agent. Evil is not as powerful as good. The Boethian conception of evil comes through evil beings such as Melkor Morgoth in The Silmarillion or Sauron ,who cannot do good things but only pervert or mock things; In The Lord of the Rings; Tolkien seems to suggest that there is no absolute evil. The other conception of evil is the Manichaen, a conception which receives more emphasis in Tolkien's trilogy and which sees the world as a battle-ground for warring forces of good and evil. Tolkien frequently personifies the Ring as if it were acting with a will of i

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