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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 Nov 05 2013
Journal Name
Wit Transaction On Ecology And The Environments, Wit, Press No. 11
Remote sensing of water quality index for irrigation usability of the Euphrates River
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irrigation use at many stations along the Euphrates River inside the Iraqi lands and to try to correlate the results with the satellite image analyses for the purpose of making a colored model for the Euphrates that can be used to predict the quality classifications of the river for irrigation use at any point along the river. The Bhargava method was used to calculate the water quality index for irrigation use at sixteen stations along the river from its entrance to the Iraqi land at Al-Qaim in Anbar governorate to its union with the Tigris River at Qurna in Basrah governorate. Coordinates of the sixteen stations of the Euphrates River were projected at the mosaic of Iraq satellite image which was taken from LANDSAT satellite for bands 1, 2

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Publication Date
Fri Apr 05 2024
Journal Name
Techhub Journal
The effect of suggested exercises on improving the kinesthetic response of soccer goalkeepers
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Publication Date
Sun Jun 20 2021
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
MULTIVARIATE ANALYSIS OF THE STEM ANATOMICAL CHARACTERS OF TERMINALIA L. (COMBRETACEAE) IN EGYPT
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A comparative investigation of the anatomical characters through a microscopical examination of the prepared transverse sections of the stem was carried out. Six plates with 32 photomicrographs were provided to convincingly show the considerable variations of anatomical characters within the nine examined species. The matrix of 18 anatomical characters which included nine quantitative and nine qualitative was applied for the clustering analysis (CA) followed by the principal component analysis (PCA) using the Multivariate Analysis of Ecological Data, PC-ORD.
The results exhibited significant variations among the species resulting in the construction of an artificial key; this key accurately represents a sufficient tool to display the

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Publication Date
Sun Mar 01 2020
Journal Name
Agricultural Engineering
Analysis of the Vacuum-Steam Defrosting Process of Plums Pre-Treated with Dehydrofreezing
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Abstract<p>The research material was prune plums (<italic>Prunus domestica</italic> L.), subjected to osmotic pre-treatment, with variable process time parameters and osmotic solution concentration. Plums thus fixed were frozen and stored for 6 months. At even (monthly) intervals, the product was defrosted by the vacuum-steam method, using the s-p-p chamber, until the thermocouple indicated a temperature of 4ºC in the sample’s thermal center. In order to study the kinetics of phenomena occurring during the defrosting process, the chamber was equipped with a measuring system to enable measurement and recording of temperature changes in time in the geometric center of the sample, as w</p> ... Show More
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Publication Date
Tue Feb 12 2019
Journal Name
Biochemical And Cellular Archives
TOXIC EFFECTS OF ABRUS PRECATORIUS EXTRACT ON LIVER AND KIDNEY OF ALBINO MICE
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Abrus precatorius L. is an important medicinal plant belonging to family Fabaceae. The present study was conducted to perform pre-clinical safety evaluation and study the pharmacological effects of the ethanolic seeds extract of A. precatorius in management of pain, psychiatric and neurological conditions. Acute toxicity was performed to study the general behavioural pattern of mice after treatment with the test extract (single doses of 1000, 2000, 3000,4000,5000 mg/kg, body weight) and sub-acute toxicity studies were performed to study the toxic effects of the test extract (1000,2000,3000 mg/kg, per os for 14 days) on different haematological parameters, body and organ weight and histopathology of liver and kidney. The toxicological evalua

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Publication Date
Thu Jan 31 2019
Journal Name
Journal Of The College Of Education For Women
Geographical distribution efficiency of the civil defense centers in the city of Baghdad
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The city suffers from the weakness of the civil defense to provide services where there are clusters of residential Guy covered services for that requires the study of the geographic distribution of the civil defense centers in Baghdad care great because they take care of Protect the population and their own property and protect state institutions. Through a review of the problems faced it is expected that this study will help decision-makers to take appropriate steps to develop this service core

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Publication Date
Tue Oct 30 2018
Journal Name
Journal Of Engineering
Study the Effect of Various Parameters on the Synthesis of ZSM-5 Zeolite
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ZSM-5 zeolite was synthesis under hydrothermal conditions at 175oC. The synthesis parameters have been investigated to find optimum synthesis method. Firstly, the crystallization time has been investigated to find the optimum crystallization time. Also, the ageing time was studied. The morphology, structure, and composition of the synthesized ZSM-5 zeolite were characterized using scanning electron microscopy (SEM), pH meter, viscometer, and X-ray powder diffraction (XRD). The bulk Si/Al ratio of ZSM-5 zeolite was in the range of 9.5—11.7. The synthesized ZSM-5 zeolite with appropriate ageing time could adjust crystal size and degree of the crystallinity. The crystal size of ZSM-5 zeolite obtained at an agei

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Publication Date
Sun Jun 05 2011
Journal Name
Baghdad Science Journal
Toxicity effects of some heavy metals on the growth of alga Scenedesmus dimorphus
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The toxicity effect of some heavy metals (Lead, Cadmium, Copper, and Zinc) on the growth of alga Scenedesmus dimorphus which belongs to the Division of Chlorophyta was studied and depended on the total cell number . The growth rate and doubling time were also calculated accordingly in present of absent of the the heavy metals . There were differences in toxic effects of the metals (p<0.05) . The growth was decreased gradually with alga when exposured to Lead at 15,20 and 25 mg/l in comparison with the control , mean while 30 mg/l caused an acute decrease in growth . Treating the alga with 0.05,0.1,0.5 mg/l concentration of Cadmium the number of cells decreased while at 1 mg/l the effect was more pronounced . As for Copper the conc

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Publication Date
Tue Feb 17 2026
Journal Name
Journal Of The College Of Basic Education
Effect of amino acids (Bcaa) on some physical abilities of advanced futsal players
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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Effect of Aspirin drug in Liver tissue of swiss white mice Mus musculus
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This study was designed to identify the extent of the effect of drug Acetylsalicylic acid (aspirin) on histological structure of liver in Swiss albino mice Mus musculus.(16) mice were used and divided into two groups. The first groupwas orally treated with )0.5ml(of aspirinat concentration of (50 mcg / kg) and the second group was considered as control group Treated with distiled water lasted for 30 days. Treatment with Aspirin led to the occurrence of histopathological cases included liver necrosis ,cellular infilitration, congestion in central vein and a case of Hemorrhage. The results also showed the absence of radial arrangement of the constituents of hepatic cells from tissue due to these changes with the control group.

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