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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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Sun Apr 01 2007
Journal Name
Journal Of Engineering
Effect of Prestressing Force on Torsion Resistance of Concrete Beams
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Sun Jan 27 2019
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Journal Of The College Of Education For Women
The issue of creation of AL-Muatazala and AL-Shaira
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words of God the Quranic text , is genera words have many faces and connotations a ccording to references, cutures and Ages.That the Quranic text is fixed , But the connotations are moveable the scientists agreed about the miracle of the Qurantic text , But they differd of the Position of miracLe including the muatazala and Al- Ashaira who have adopted the idea of sytem and miracle of linguistic . Most of them were lingustics, grammerians and writers as: AL- Jahith, AL- Faraa Abivbeida , Ibn kutaba , AL -Rumani , AL -katabi , AL- Bakilaai , AL- Gargani and Others.
They also differed in what the words of Allaah mean . Is the Quranic text creature or updated ,it is the issue that exhausted the effort.of muslim scientists though its imbo

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Tue Jul 01 2014
Journal Name
Bulletin Of The Iraq Natural History Museum
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Thu Oct 08 2020
Journal Name
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Tue Jan 29 2019
Journal Name
Journal Of The College Of Education For Women
The Cognitive Conception Anxiety of the University of Baghdad Students
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The rabid development in life and technology arouse the anxiety, stress, and fear of people. Accordingly the maladjustment and deceived conceptions appear in their behaviors which influence their selves and others.
These changes and development in society influence the university students' life, personality, thoughts and behavior. An exceeding in anxiety and fear has negative effect on everyday life activities and. negative effect on both mind and body.
The problem of the study is centered around cognitive conception anxiety of the university students.
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Publication Date
Wed Jun 30 2010
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Kinetic and Isotherm Modeling of Adsorption of Dyes onto Sawdust
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Sawdust has the ability to adsorb the dyestuff from aqueous solution. It may be useful low cost adsorbent for the treatment of effluents, discharged from textile industries. The effectiveness of sawdust has been tested for the removal of color from the wastewater samples containing two dyes namely Direct Blue (DB) and Vat Yellow (VY). Effect of various parameters such as agitation time, adsorbent dose and initial concentration of each dye has been investigated in the present study. The adsorption of dyes has been tested with various adsorption isotherm models. The Langmuir isotherms model is found to be the most suitable one for the dye adsorption using sawdust and the maximum adsorption capacity is 8.706 mg/g and 6.975 mg/g for DB and V

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Publication Date
Fri Nov 01 2019
Journal Name
Recent Technologies In Sustainable Materials Engineering
Evaluation of Tensile Strength and Durability of Microbial Cement Mortar
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Publication Date
Mon Nov 21 2022
Journal Name
College Of Islamic Sciences
Sources of audio images in the poetry of the Islamic
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      الحمدُ للهِ رب العالمين ، والصلاة والسلام على نبيه الأمين محمد r وعلى آله الطيبين الطاهرين ، وأصحابه الغر الميامين:

             تعد الصورة السمعية مفهوما بيانيا نجده في البلاغة العربية واضحاً مؤثرا، مؤديا دورا جوهريا في إيصال الفكرة التي يروم الأديب إيصالها إلى المتلقي   ولا تبدو السمعية واضحة إلاّ إذا نظر إليها في حالة أدبيه تهز كيان الشاعر &nbsp

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Publication Date
Fri Sep 05 2008
Journal Name
Journal Of Kerbala University
Synthesis of New type of tetrazoles starting from D-ribose
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This work includes synthesis of sugar tetrazole derivative, D-ribose reacted with acetone in the presence of sulfuric acid H2SO4 to give 2, 3-O-isopropylidene-D-ribose (1). The Aldol condensation of (1) with formaldehyde in methanolic K2CO3 solution gave 2-hydroxymethyl (2, 3-O-isopropylidene-D-ribose)(2). Which was tosylated by Tosyl chloride in pyridine to yield compound (3), SN2 reaction of (3) with sodium cyanide in DMSO afforded compound (4). The [2+ 3] cycloaddition reaction of (4) with sodium azide gave the targeted compound (5). All prepared compounds have been characterized by: TLC, Specific rotation, Microelemental analysis and [FTIR and 1 H NMR spectroscopy]

Publication Date
Mon Aug 27 2018
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Synthesis, Characterization and Antibacterial Activity of Carbamate Derivatives of Isatin
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In search of novel antibacterial agent, a series of new isatin derivatives (3a-d) have been synthesized by condensation isatin (2,3-indolinendione) with piperidine (hexahydropyridine), hydrazine hydrate and Boc-amino acids respectively. Compounds synthesized have been characterized by IR spectroscopy and elemental analysis. In addition, the in vitro antibacterial properties have been tested against E. coli, P. aeruginosa, and Bacillus cereus, S. aureus by employing the well diffusion technique. A majority of the synthesized compounds were showing good antibacterial activity and from comparisons of the compounds, compound 3d has been determined to be the most active compound.

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