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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 Mar 01 2014
Journal Name
International Journal Of Advanced Research
Ex vivo study of the importance of sphingolipid in Leishmania amastigote
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Leishmania is the causative agent of leishmaniasis, a widely distributed disease. Amastigote forms of Leishmania are intracellular and reside within the macrophage of the vertebrate host. Previous studies showed that certain Leishmania species may scavenge host factors for survival, specially sphingolipids, the key element of the eukaryotic membranes. In this study we have investigated the survival of new world L. mexicana amastigotes in murine macrophage cell-line in the presence and absence of foetal bovine serum (FBS). Results showed that there was no significance in the infectivity of amastigotes and also the number of parasite per cell; such findings suggest that L. mexicana amastigotes have its own pathway of sphingolipid intake and c

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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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Publication Date
Thu Jan 30 2014
Journal Name
Al-kindy College Medical Journal
Efficacy & safety of Desmopressin in the treatment of pediatric nocturnal enuresis
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Back ground: primary nocturnal enuresis (PNE) is a socially distressing condition that can be troubling for children & their families. It affects 15-26% of five years olds. Several approaches are used to treat PNE including behavioral modification, alarms & drug therapy. Aim of the study: to determine the efficacy and safety of nasal desmopressin treatment in children with PNEPatients : fifty-four children with primary nocturnal enuresis with a mean age of ( 8.2) years ( range 6-15), underwent a 2 week observation period followed by entrance into a randomized controlled study, comparing desmopressin & placebo, lasting 4 weeks. The efficacy of the drug was measured in reduction of the number of wet nights per week. The enureti

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Publication Date
Tue Jul 01 2014
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
SURVEY OF THE GENUS PHYTOMYZA FALLEN,1810 (DIPTERA: AGROMYZIDAE) OF IRAQ
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    The aim of this study to survey the leaf miner Phytomyza Fallen of Iraq, many leaf plants which infested by leaf miners  were collected from several regions of Iraq.  The paper showed there are  four species of this genus during the work: Phytomyza horticola Gourear,1840; Ph. atricornis Meigen, 1838; Ph. rufipes Meigen,1830; Ph. ranunculi (Schrank,1803)

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Publication Date
Tue Dec 30 2008
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Design Criteria of an Activated Carbon Bed for Dechlorination of Water
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Granular carbon can be used after conventional filtration of suspended matter or, as a combination of filtration - adsorption medium. The choice of equipment depends on the severity of the organic removal problem, the availability of existing equipment, and the desired improvement of adsorption condition.
Design calculations on dechlorination by granular - carbon filters considering the effects of flow rate, pH , contact time, head loss and bed expansion in backwashing , particle size, and physical characteristics were considered assuming the absence of bacteria or any organic interface .

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Publication Date
Thu May 18 2023
Journal Name
Journal Of Engineering
Field Study of Novel Storage Tank of Solar Water Heating System
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In this paper thermo-hydrodynamic characteristics were investigated experimentally for a new type shell-helical coiled tube heat exchanger used as a storage tank of closed loop solar water heater system. Triple concentric helical coils were made of copper tubes of (12.5mm OD and 10mm ID) with coils diameter of (207, 152.2, 97mm) for outer, middle and inner coils respectively. The experiments were carried out during a clear sky days of (March and April 2012). The parameters studied in this work are: history of average temperature of shell side of the storage tank, collector heat gain, heat rejected from coils to shell side of the storage tank, collector efficiency, thermal effectiveness of the heat exchanger (storage tank), and pressure d

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Publication Date
Sat Mar 30 2002
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Study of the Factors Affecting the Efficiency of Reverse Osmosis Process
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Publication Date
Sat Mar 19 2022
Journal Name
Al-khwarizmi Engineering Journal
The Effect of Mass Ratio on Phytoremediation of Nickel Contaminated Water
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Water pollution is one of the global challenges that the society must address in the 21st century aiming to improve the water quality, reduce human pollutants and ecosystem health impacts. In phytotoxicity test, the plant of Iresine herbstii was exposed to remove nickel from simulated wastewater using two different ratios (mass of plant to the mass of nickel) (,Rp/Ni) for 21 days with sub-surface batch system. During the exposure period, the removal of Ni concentrations (2, 5 and 10 mg/L) for two mass ratio (2,800 and 34,000) were (83.6%, 77.2%, 78.0%) and (86.8%, 97% and 95.6%), respectively. final result of the rate was found that the highest removal occurred, 97%, at a mass ratio of 34,000 and

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Publication Date
Mon Jan 01 2018
Journal Name
Journal Of Cosmetics, Dermatological Sciences And Applications
Treatment of Kaposi’s Sarcoma by Combination of Zinc Sulfate and Propranolol
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Publication Date
Fri Mar 01 2019
Journal Name
Al-khwarizmi Engineering Journal
Study of Fatigue Fractography of Mild Steel Used in Automotive Industry
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Fatigue failure is almost considered as the predominant problem affecting automotive parts under dynamic loading condition. Thus, more understanding of crack behavior during fatigue can strongly help in finding the proper mechanism to avoid the final fracture and extent the service life of components. The main goal of this paper is to study the fracture behavior of low carbon steel which is used mostly in automotive industry. For this purpose, the fractography of samples subjected to high and low stress levels in fatigue test then was evaluated and analyzed. Hardness and tensile tests were carried out to determine the properties of used steel. Also, the samples were characterized by microstructure test and XRD analysis to examine the con

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