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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
Tue Mar 15 2011
Journal Name
Wassit Journal For Humanities
A Trace of Modern European Literary Currents in Arthur Miller's Death of a Salesman
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Publication Date
Fri Mar 31 2023
Journal Name
Iraqi Geological Journal
Subsurface Structural Image of Galabat Field, North East of Iraq Using 2D Seismic Data
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This research had been achieved to identify the image of the subsurface structure representing the Tertiary period in the Galabat Field northeast of Iraq using 2D seismic survey measurements. Synthetic seismograms of the Galabat-3 well were generated in order to identify and pick the reflectors in seismic sections. Structural Images were drawn in the time domain and then converted to the depth domain by using average velocities. Structurally, seismic sections illustrate these reflectors are affected by two reverse faults affected on the Jeribe Formation and the layers below with the increase in the density of the reverse faults in the northern division. The structural maps show Galabat field, which consists of longitudinal Asymmetrical narr

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Publication Date
Thu Jan 01 2015
Journal Name
Journal Of Faculty Of Medicine Baghdad
Outcome of buccal mucosal patch graft in the Management of recurrent hypospadias urethrocutaneous fistula
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Background: urethrocutaneous fistula after hypospadias surgery repair is the most common complication and remains a frustrating problem for surgeon and the patient. The problem is exacerbated because the urethrocutaneous fistula may recur which adds more demands surgery. Objectives: The purpose of this study is to evaluate of the use of oral mucosal graft for management of recurrent urethrocutaneous fistula after hypospadias repair. Patients and Methods: twelfth patients with age ranging from 4 year to 15 years were presented with history of recurrent fistula. Most of fistula were located in proximal penile and penoscrotal region (58.3%) . those patients were repaired by using oral mucosal graft with mean postoperative follow up period up t

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Fri Dec 03 2021
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The Skill of Making a Decision and its Relationship of Academic Achievement Among Students
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Thu Jan 01 2015
Journal Name
Iraqi Postgraduate Medical Journal
Effects of Coriandrum Sativum on the Spermatogenesis of Rat Testis: Histological and Morphometrical Studies
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ABSTRACT: BACKGROUND: Coriandrum Sativum is a native of Mediterranean region and is grown in North Africa, central Europe, and Asia as culinary herb and medicament. In addition to the other health-supporting reputation, coriander has hypoglycemic, hypolipidemic, and aphrodisiac effects. OBJECTIVE: To study the effect of Coriandrum Sativum on process of spermatogenesis. MATERIALS AND METHODS: Coriandrum sativum was given daily to mature male rats in a dose of 50mg/ 100g body weight for 14 days. 10% formalin fixed paraffin-embedded tissue sections were performed for histological and morphometrical studies. RESULTS: Histological study showed wider seminiferous tubules & increased spermatocytes population with an increased sperm density

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Wed Mar 18 2020
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Natural Products of Lactococcus Overcome Nosocomial Infection in Some of Baghdad Hospitals in Iraq
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Nosocomial infections (NIs) are hospital-acquired associated infections, and also contracted due to the infections or toxins that exist in some location, like hospital. Therefore in our study, 4 Lactic acid bacteria (LAB) isolates were obtained from dairy product (Lactobacillus brevis, L. acidophilus, Lactococcus raffinolactis and Lactococcus lactis) and were tested for Bacteriocin production to select Lactococcus lactis among them. Cell free supernatant (CFS), Lipid and partial purification of protein La. Lactis had high inhibitory effect against test pathogens (E. coli, Bacillus cereus, Staphylococcus aureus and Streptococcus). 30 isolates that diagnosed by Vitec, were isol

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Publication Date
Sat Oct 01 2011
Journal Name
Iraqi Journal Of Physics
The Role of Annealing Temperature on the Optical Properties of Thermally Deposited CdTe Films
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A polycrystalline CdTe film has been prepared by thermal evaporation technique on glass substrate at substrate temperature 423 K with 1.0 m thicknesses. The film was heated at various annealing temperature under vacuum (Ta =473, 523 and K). Some of physical properties of prepared films such as structural and optical properties were investigated. The patterns of X-ray diffraction analysis showed that the structure of CdTe powder and all films were polycrystalline and consist of a mixture of cubic and hexagonal phases and preferred orientation at (111) direction.
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Publication Date
Sat Dec 01 2018
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Obstacles of banking insurance and its affection analysis of financial ratios in insurance companies
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Find the impediments Activity vital and important, but focuses a bancassurance activity, diagnosis and its impact on the financial ratios indicators for insurance companies. The researcher has adopted in his research on several financial ratios used to analyze the financial performance of a (relative profitability, liquidity ratio and the ratio of solvency) of the company Iraqi insurance for a period of one year (2009) to a year (2015), based on the annual reports and financial statements (balance sheet revealed income), financial statements for insurance premiums for banks research sample of this research has addressed several topics of theoretical and practical body through which the researcher obstacles to banking and insurance experi

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Sat Oct 19 2024
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Synthesis, Characterization and Study of Thermal Properties of New Silicone Polymers and Their Nanocomposites
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Fri Mar 01 2024
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On Existence of Prime K-Tuples Conjecture for Positive Proportion of Admissible K-Tuples
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Number theorists believe that primes play a central role in Number theory and that solving problems related to primes could lead to the resolution of many other unsolved conjectures, including the prime k-tuples conjecture. This paper aims to demonstrate the existence of this conjecture for admissible k-tuples in a positive proportion. The authors achieved this by refining the methods of “Goldston, Pintz and Yildirim” and “James Maynard” for studying bounded gaps between primes and prime k-tuples. These refinements enabled to overcome the previous limitations and restrictions and to show that for a positive proportion of admissible k-tuples, there is the existence of the prime k-tuples conjecture holding for each “k”. The sig

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