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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
Sat Jan 01 2011
Journal Name
Journal Of Environmental Engineering
Influence of Clay Lens on Migration of Light Nonaqueous Phase Liquid in Unsaturated Zone
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Publication Date
Thu Jun 30 2016
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
The Effect of Asphaltene on the Stability of Iraqi Water in Crude Oil Emulsions
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In the present work, asphaltenes and resins separated from emulsion samples collected from two Iraqi oil wells, Nafut Kana (Nk) and Basrah were used to study the emulsion stability. The effect of oil resins to asphaltene (R/A) ratio, pH of the aqueous phase, addition of paraffinic solvent (n-heptane), aromatic solvent (toluene), and blend of both (heptol) in various proportions on the stability of emulsions had been investigated. The conditions of experiments were specified as an agitation speed of 1000 rpm for 30 minutes, heating at 50 °C, and water content of 30%.  The results showed that as the R/A ratio increases, the emulsion will be unstable and the amount of water separated from emulsion increases. It was noticed that the em

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Publication Date
Sun Jul 01 2001
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
HAEMOPROTEIDS OF THE AVIAN FAMILY RALLIDAE IN IRAQ WITH DESCRIPTION OF A NEW SPECIES
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A survey of haemoproteids among the eight species of Iraq rallids were carried out in the
middle, south, and west of Iraq. Two haemoproteods were recorded, Haeomproteus porzanae
(Galli-Valerio, 1907) as a new record for Iraq and the new species H. baghdadensis described
from Fulica atra L. collected in the middle of Iraq.

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Publication Date
Sat Oct 01 2022
Journal Name
Al–bahith Al–a'alami
THE MENTAL IMAGE OF THE IRAQI PUBLIC CONCERNING THE HOUSE OF REPRESENTATIVES: (Section I)
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This research is a result of other studies made about the iraqi public and its relationship with different states institutions, until recently, such studies were almost non-existent. The main characteristic that distinguishes scientific research is that it involves a specific problem that needs to be studied and analysed from multiple aspects. What is meant by identifying the problem, is to limit the topic to what the researcher wants to deal with, rather than what the title suggests as topics which the researcher doesn’t want to deal with. The problem of this research is the absence of thoughtful and planned scientific programs to build a positive mental image of the institutions of the modern state in general and the House of Represe

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Publication Date
Sat Nov 03 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Prevalence of Hypochondriasis Disorder among Iraqi Former Prisoners of Iraq-Iran War, 1980-1988
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Objective : To find out the prevalence of Hypochondriasis among Iraqi repatriated prisoners of
Iraq-Iran war, and the relationship with some variables.
Methodology: A descriptive study was carried out from Jan. 2nd , 2006 through May 4th , 2006. A
non-probability accidental sample of 400 repatriates who had visited; Ministry of Human Rights,
Ministry of Health, and Ministry of Defense. A questionnaire was constructed for this purpose, which
consisted of 6 items for demographic data, and 14 items for measuring Hypochondriasis. Reliability
and validity of the questionnaire had been determined through the pilot study (Test and retest) and the
experts panel. Data were collected with using the constructed questionnaire an

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Publication Date
Sun Dec 05 2010
Journal Name
Baghdad Science Journal
Effect of parasites on the of digestive system in Iraqi bulbul Pycnonotus lecuotis mesoptamiae
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This study included collecting of 150 specimens of the Iraqi Bird Bulbule Pycnonotus lecuotis mesoptamiae (Pycnotidae , Passeriformes), from the 1st of November 2004 to 30th of October 2005 in the city of Baghdad and its suburbs, in concern of identifying the internal parasite of the digestive tract of these birds and studying the diseases resulted from the infection. The study showed that the bird Bulbule is Parasitized by Four types of Cestodes ,two of them are recorded in this kind of bird in Iraq for the first time ,Paradicranotinae anormalis and Haploparaxis sp. , and the other two are Raillietina tetragona and Allohymenolepsis sp. ,and by two types of Pin Worm(Trematode) that are identified for the first time in the Bird Bulb

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Publication Date
Wed Jun 01 2022
Journal Name
Journal Of The College Of Languages (jcl)
Concept of Time in the Poetry of Abdulhaq Hamid: Abdülhak Hamid'in Şiirlerinde Zaman İncelenmesi
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     After Organization literature era, two literary schools appeared in Turkey and Abdulhaq Hamid is one of this period most prominent poets. During his stay in France with a group of colleagues sent by Turkish Government, he was greatly influenced by the French modern literature and the French modern literary authors.

     The study discusses the concept of time in the poetry of Abdulhaq Hamid. Reading his poetry, it can be noticed that time is important where he frequently refers to day and night, morning and evening as time insinuations. Hence, the present paper gives a brief study of the poet’s life, and sheds lights on his poems that deal with time- concept.

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Publication Date
Thu Apr 21 2016
Journal Name
Iraqi Journal Of Agricultural Sciences
EFFECT OF SHEEP MANURE EXTRACT ON THE GROWTH AND NUTRIENTS CONTENT OF TOMATO SEEDLINGS
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The experiment was conducted under shading (with the aid of Saran) condition on a nursery managed by the Baghdad Mayoralty during the season of 2014-2015 to study the effect of composed sheep manure extract on the growth and leaf nutrients content of tomato seedlings var. Wijdan. The experiment was composed of 6 treatments included the extract of sheep manure by hot (425C)and lmbient(205C) temperature water .The extract was diluted to the half by water and foliar applied to seedlings (multible application) or to the soil . Treatments also included the application of NPK chemical fertilizers as recommended and a control treatment through applying distilled water as foliar .The experiment was designed according to the randomized compl

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Publication Date
Fri Jul 21 2023
Journal Name
Journal Of Engineering
Study the Effect of Ceramic Coating on the Performance and Emissions of Diesel Engine
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In this study, the effect of ceramic coating on the performance and gases emission on diesel engine was investigated. A four-stroke, direct injected, single cylinder, diesel engine was tested at constant speed and at different load conditions without coating. Then, the inlet and exhaust valves faces were coated by about 500µm with ceramic materials. Ceramic layers were made of YttriaStabilized Zirconia (YSZ), and NiCrAl as a bond coat. The coating technique adapted in this work is the flame spray method. The engine with valves ceramiccoated research was tested for the same operation conditions of the engine (without coating). The results indicate a reduction in both fuel consumption by about 7.6% and particulate emissions by about (13

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Publication Date
Sun Jun 30 2013
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
The Effect of Promoters on the Activity of Prepared Zeolite Catalyst in FCC Process
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Faujasite type NaY zeolite catalyst was prepared from locally available kaolin, then the prepared NaY zeolite have been modified by exchanging of sodium ion with ammonium to produce NH4Y zeolite. NH4Y zeolite was converted to HY zeolite by ion exchanging with oxalic acid. Zinc and nickel promoters have been added to the prepared HY zeolite catalyst, and the effect of these promoters on the catalytic activity of the prepared HY catalyst was studied in fluid catalytic cracking process using light gas oil as a feedstock. The experimental results show that the promoted catalyst gives higher gas oil conversion and gasoline yield than HY zeolite catalyst at the same reaction temperature and WHSV. It was also found that the promoted catalyst gi

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