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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 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
Histological and histomorphometric studies of the effects of hyaluronic acid on osseointegration of titanium implant in rabbits
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Background: One of the unique prosthesis for tooth or teeth replacement is the dental implant. Our attempt is using a biomaterial system that is easily obtained and applicable and has the ability to provoke osteoinductive growth factor to enhance bone formation at the site of application. One of these natural polymers is hyaluronic acid. Material and methods: Sixty machined surface implants from commercially pure titanium rod inserted in thirty NewZealand rabbits. Two implants placed in both tibia of each rabbit. The animals scarified at 1, 2 and 4 weeks after implantation (10 rabbits for each interval). For all of animals the right tibia’s implant was control (uncoated) and the left one was experimental (coated with 0.1ml Hyaluro

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Publication Date
Sun Jan 01 2023
Journal Name
Aip Conference Proceedings
Impact of geographical locations of the water treatment plants in Baghdad City on quality of supplied water
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In this study, the water treatment plants located on the Tigris River within Baghdad city were subjected to qualitative and quantitative assessments. Based on location, the plants from upstream to downstream are Al-Karkh, East Tigris, Al-Karamah, Al-Wathbah, Al-Wehdah, Al-Kadiseyah, Al-Dora, and Al-Rashid. Data from 2009 to 2020 on the turbidity, total dissolved solids, Alkalinity, hardness, chloride, calcium, and temperature were used in the qualitative assessment while data on the treated water production and population served were used in the quantitative assessment. The above Data was acquired from the Municipality of Baghdad. The turbidity was mainly used as a fair gauge to assess the performance of the water treatment plants in Baghda

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Publication Date
Sun Oct 02 2011
Journal Name
Journal Of Educational And Psychological Researches
The Effect of a consulting program for decreasing withdrawal behavior of the children with autism of kindergarten
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       unacceptable social behaviors, particularly withdrawal behavior that appears in children with autism represent a major problem hindering the process of communication with those around them and therefore the process of mergence  with them be difficult.

     The withdrawal causes a real affect deficit for children with autism limits the possibility of development of their intellectual and mental growth due to their solitude and the weakness of their focus in the acquisition of pedagogical skills and lack the necessary social skills to maintain the relations of friendship and enjoyment of them.

      withdrawal children fail to participate

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Publication Date
Thu Dec 01 2016
Journal Name
Journal Of Engineering
Numerical and Experimental Investigations of the Effect of PVD and Vacuum Pressure on the Degree of Saturation
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    Soft clays are generally characterized by low shear strength, low permeability and high compressibility. An effective method to accelerate consolidation of such soils is to use vertical drains along with vacuum preloading to encourage radial flow of water.  In this research numerical modeling of prefabricated vertical drains with vacuum pressure was done to investigate the effect of using vertical drains together with vacuum pressure on the degree of saturation of fully and saturated-unsaturated soft soils.  Laboratory experiments were conducted by using a specially-designed large consolidometer cell where a central drain was installed and vacuum pressure was applied. All tests were conducted

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Publication Date
Sat Dec 02 2023
Journal Name
Kufa Journal Of Arts
The Figurative Metaphor in the Discourse of Enlightenment of Hashem Salih in the Light of Cognitive Linguistics
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Publication Date
Fri Jul 21 2023
Journal Name
Journal Of Engineering
The Effect of Different Types of Aggregate and Additives on the Properties of Self-Compacting Lightweight Concrete
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The major aim of this research is study the effect of the type of lightweight aggregate (Porcelinite and Thermostone), type and ratio of the pozzolanic material(SF and HRM) and the use of different ratios of w/cm ratio(0.32 and 0.35) on the properties of SCLWC in the fresh and hardened state. SF and HRM are used in three percentage 5%,10%, and 15% as a partial replacement by weight of
cement for all types of SCLWC. The requirements of self-compatibility for SCC are fulfilled by using the high performance superplasticizer (G51) at 1.2liter per 100 kg of cement. The values of air dry density and compressive strength at age of 28 days within the limits of structural lightweight concrete. The air dry density and compressive strength at a

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Publication Date
Sun Dec 01 2019
Journal Name
Baghdad Science Journal
Diversity, Abundance, and Distribution of Cladocera at the end of the Tigris River North of Basrah – IRAQ
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Seasonal variations of the species composition and abundance of Cladocera were studied in two stations at the end of the Tigris River and one station at the confluence of the Tigris with Euphrates area, at the beginning of the Shatt Al-Arab River in Al-Qurnah North of Basrah Province, from October 2015 to August 2016. Samples of zooplankton were collected by plankton net 100-µm. mesh size. The population density of Cladocera ranged between 1 Ind /m³ during summer and 211 Ind./m³ during winter at station 1 (Al-Jewaber Bridge). A total of 16 species of Cladocera belonging to 12 genera were recorded in the study. The average density of Cladocera ranged from 23.2 ind./m3 at Station 2 (Hamayon Bridge) to 53.7 Ind./m3

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Publication Date
Tue Jan 01 2019
Journal Name
Biochemical And Cellular Archives
Effect of cultar on growth and production of two cultivars of Ranunculus plant under different environmental conditions
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Publication Date
Sun Dec 04 2016
Journal Name
Baghdad Science Journal
The Efficiency of Terpenes Extracts of Eucalyptus Camaldulensis Seed to control Larval Stage of Callosobruchus maculates (Coleoptera:Bruchidae)
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The current study has beenconduced to evaluate the effect of extracted crude terpens at the concentrations of 6,8% of seeds of Eucalyptuscamaldulensison the 4th larval instar oftheCallosobruchusmaculates and the percentage of the cowpea seed germination.The Results showed that the terpens extract of the concentration of 8% increases the mortality rate of the fourth larval instar and it reach to 63.3%, and then decrease of to 26.6,20% at concentration of 6%and forcontrol treatment respectively The percentage of adult emergence reduces to 0% at the concentration of 8% compared with control treatment in which it reach to 66.6%. The extraction atbothconcentrations 6,8% does not affect the germination rate

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Publication Date
Tue Nov 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
mathematical model for segmentation of the overall planning of puplic redemption company- ministry of industry and minerals
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Abstract

The study presents a mathematical model with a disaggregating approach to the problem of production planning of a fida Company; which belongs to the ministry of Industry. The study considers disaggregating the entire production into 3 productive families of (hydraulic cylinders, Aldblatt (dampers), connections hydraulics with each holds similar characteristics in terms of the installation cost, production time and stock cost. The Consequences are an ultimate use of the available production capacity as well as meeting the requirements of these families at a minimal cost using linear programming. Moreover, the study considers developing a Master production schedule that drives detailed material and production requi

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