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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 2022
Journal Name
Ssrn Electronic Journal
Developing a Predictive Model and Multi-Objective Optimization of a Photovoltaic/Thermal System Based on Energy and Exergy Analysis Using Response Surface Methodology
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Fri Jan 01 2021
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FORECASTING THE EXCHANGE RATES OF THE US DOLLAR AGAINST THE IRAQI DINAR USING THE BOX-JENKINS METHODOLOGY IN TIME SERIES WITH PRACTICAL APPLICATION
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The goal of the study is to discover the best model for forecasting the exchange rate of the US dollar against the Iraqi dinar by analyzing time series using the Box Jenkis approach, which is one of the most significant subjects in the statistical sciences employed in the analysis. The exchange rate of the dollar is considered one of the most important determinants of the relative level of the health of the country's economy. It is considered the most watched, analyzed and manipulated measure by the government. There are factors affecting in determining the exchange rate, the most important of which are the amount of money, interest rate and local inflation global balance of payments. The data for the research that represents the exchange r

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Sun Mar 03 2013
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Sedimentological and diagenetic study of the Early Middle Miocene Jeribe Limestone Formation in selected wells from Iraq northern oilfields (Ajil; Hamrin; Jadid; Khashab)
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Five subsurface sections covering the entire length of the Jeribe Limestone Formation (Early Middle Miocene) were studied from four oilfields in northern Iraq. It is hoped to unravel this formation microfacies ; depositional environment; diagenetic attributes and their parental processes; and the relationship between these processes and the observed porosity patterns. The microfacies were found to include mudstone, wackestone, packstone, and grainstone, which have been deposited respectively in open platform, restricted platform, and edge platform which represent the lagoonal environment, while the deposits of the lower parts of the Jeribe formation especially in well Hamrin- 2 reflect a deeper fore slope environment. By using the lithofac

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Mon Dec 31 2012
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Experimental Study on the Impact of External Geometrical Shape on Free and Forced Convection Time Dependent Average Heat Transfer Coefficient during Cooling Process
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In this research, an experimental study was conducted to high light the impact of the exterior shape of a cylindrical body on the forced and free convection heat transfer coefficients when the body is hold in the entrance of an air duct. The impact of changing the body location within the air duct and the air speed are also demonstrated. The cylinders were manufactured with circular, triangular and square sections of copper for its high thermal conductivity with appropriate dimensions, while maintaining the surface area of all shapes to be the same. Each cylinder was heated to a certain temperature and put inside the duct at certain locations. The temperature of the cylinder was then monitored. The heat transfer coefficient were then cal

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Thu Nov 01 2012
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Lactic Acid 5% Mouthwash is an Effective Therapeutic and Prophylactic Agent in Treatment of Recurrent Aphthous Ulcer (Single blind placebo controlled therapeutic study)
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Synthesis and Characterization of Some Metal Complexes with their Sulfamethoxazoleand 4,4'-dimethyl-2,2'-bipyridyl and study Cytotoxic Effect on Hep-2 Cell Line
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The ligand 4-amino-N-(5-methylisoxazole-3-yl)-benzene-sulfonamide(L1) (as a chelating ligand) was treated with Pd(II),Pt (IV) and Au(III) ions in alcoholic medium in order to prepare a series of new metal complexes. Mixed ligand complexes of this primary ligand were prepared in alcoholic medium in presence of the co-ligand 4,4'-dimethyl-2,2'-bipyridyl(L2) with Cu(II) ,Pd(II) and Au(III) ions. The complexes were characterized in solid state using flame atomic absorption, elemental analysis C.H.N.S, FT-IR, UV-Vis Spectroscopy, conductivity and magnetic susceptibility measurements. The nature of some complexes formed in ethanolic solution has been studied following the molar ratio method, also stability constant was studied and the complexes f

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Sat Aug 01 2020
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Humic acid coated sand as a novel sorbent in permeable reactive barrier for environmental remediation of groundwater polluted with copper and cadmium ions
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Plantation of humic acid nanoparticles on the inert sand through simple impregnation to obtain the permeable reactive barrier (PRB) for treating of groundwater contaminated with copper and cadmium ions. The humic acid was extracted from sewage sludge which is byproduct of the wastewater treatment plant; so, this considers an application of sustainable development. Batch tests signified that the coated sand by humic acid (CSHA) had removal efficiencies exceeded 98 % at contact time, sorbent dosage, and initial pH of 1 h, 0.25 g/50 mL and 7, respectively for 10 mg/L initial concentration and 200 rpm agitation speed. Results proved that physicosorption was the predominant mechanism for metals-CSHA interaction because the sorption data followed

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Mon Dec 14 2020
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Healthy lifestyle behaviors are major predictors of mental wellbeing during COVID-19 pandemic confinement: A study on adult Arabs in higher educational institutions
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In the past infectious diseases affected the quality of lifestyle during home confinement. The study conducted examines the influence of home confinement during the COVID-19 pandemic outbreak on lifestyle, mental wellbeing, nutritional status, and sleeping pattern.

Method

An online multicategorical questionnaire was distributed to collect demographic information combined with the following tools: Food Frequency Questionnaire (FFQ), International Physical Activity Questionnaire (IPAQ), WHO-5 wellbeing score, and Pittsburgh Sleep Quality Index (PSQI). A snowball non-discriminate sampling procedure was

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The Evaluation of the immune response in Golden Hamsters experimentally infected with Leishmania donovani was determined in this study, particularly, the cellular immune response. Follow up has maintained to determine the Delayed Type of Hypersensitivity using skin test both in infected and control lab animals. Chicken red blood cells were used as a parameter to evaluate the immune system; they are dull and have the ability of immunization. Two concentrations of chicken R.B.C were examined to determine which gives the higher titration in Hamsters and those were 1.5 X 109 cell/ml and 3 X 109 cell/ml , the second concentration gave the maximum titration where then used in this work. After sensitization with Chicken R.B.C for both infected a

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Thu Oct 12 2017
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A field experiment was carried out during two winter season 2013, 2014 at the field of the Department of Field Crops, College of Agriculture, University of Baghdad, to study the effect of seeds soaking with Gibberellic acid and foliar with Abscisic Acid on the growth, yield, and content of Anise oil seeds using factorial experiment within RCBD design with three replicates. The seeds was treated within GA3 were soaked with two concentrations of  30, and 60 mg. litter-1 in addition to without soaking and the code has been B0 , B1 , B2 overlapped these transactions with two concentrations of Abscisic Acid  3, and 6 mg. litter-1 in addition to without foliar A0 , A1 , A2The seeds to be treated  with GA3 are soaked for 24 hours prior

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