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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
Wed Jan 01 2025
Journal Name
International Journal Of Applied Science And Engineering
Assessment of the properties of asphalt mixtures modified with LDPE and HDPE polymers
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The performance of asphalt pavements is crucial due to heavy traffic loads from civil and industrial developments. Various additives and modifiers are used in flexible roads to improve their resistance to deterioration caused by climatic changes. From this context, modifying the asphalt binder with polymers is popular in asphalt pavement construction. The present research investigates the effect of Polyethylene (PE) polymers in powder form on the characteristics of asphalt mixtures since these polymers are composed of hydrocarbons. It is similar to asphalt binders, making them very effective in enhancing the performance of neat asphalt produced from the oil refinery. To confirm this, two types of PE, High-Density PE (HDPE) and Low-Density P

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Publication Date
Sun Jun 01 2008
Journal Name
Baghdad Science Journal
Effect of Nitrogen Fertilizer and Plant Density on Yield and Growth of Sunflower
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The effect of nitrogen fertilizer and the planting distance on growth and yield of the sunflower cultivar (Taka) was investigated. The experiment was conducted in the field using five nitrogen fertilizer levels (0, 50, 100, 150, 200) kg/donum and three planting distances (10, 20, 30) cm/plant. The experiment design was split-plot by using RCBD with four replicates. The level of fertilizer as the main plot, while the planting distance as the sub plot. Plant high and yield components were measured. Results indicated that using 200 kg/donum of nitrogen and 30 cm/plant of planting distance gave the highest rate of 1000 seeds weight and the number of seeds/ head. While using 200 kg/donum of nitrogen fertilizer with 10 cm/plant of planting dista

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Publication Date
Thu Aug 04 2022
Journal Name
Journal Of Business And Management Studies
The Role of Free Trade Zones in Activating Sources of Income in Iraq
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Many countries, including the Arab countries, have sought to establish the free zones because of their important economic importance to diversify financial income, especially in rentier countries, in light of the trend towards the capitalist economy in light of what has been produced by economic globalization, in addition to that many Arab countries have turned towards establishing the free zones that many countries of the world have turned to, to support their economy, especially in the field of attracting foreign investments for these regions, and using them in transferring modern technology, and operating the national workers of the countries that have established those areas, and adopting their products in meeting the needs of t

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Publication Date
Tue Feb 17 2026
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Effect of Temperature and Frequency on the Dielectric Properties of PVC/MnCl2 Composite
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Publication Date
Fri Feb 01 2019
Journal Name
Indian Journal Of Natural Sciences
Design and Test of Electrochemistry of Electrodes Catalysis for an Alkaline Fuel Cell
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Publication Date
Wed Jun 30 2021
Journal Name
Gsc Biological And Pharmaceutical Sciences
Checklist of the Umbelliferae family in the herbarium of Iraq natural history museum
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The aim of this study is to make the inventory for Umbelliferae family for the purpose of identifying the samples that were collected over long periods and saved in the herbarium of Iraq Natural History Museum/ University of Baghdad. We found that the herbarium plants were very large and varied from different parts for Iraq, in different and varied environments, which collected and arranged according to a very specific system in the herbarium for remaining an important source to all graduate students and researchers to take advantage for these plants. Also, the flowering and fruiting periods for these plants in Iraq were recorded in different regions. Most these plants begin to flower in the spring and thrive at fields and farms.

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Publication Date
Fri Jan 28 2022
Journal Name
Gsc Biological And Pharmaceutical Sciences
Review with checklist of monocot in the herbarium of Iraq Natural History Museum
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This study was conducted to make an inventory of the monocot plants that were collected before and now which stored in the herbarium of Iraq Natural History Museum for identifying them. The herbarium contains avery large and varied number of plants from different parts in Iraq and for different and varied environments. The plants collected, arranged and identified using taxonomic keys specific to these families. Currently, the plant samples are in the herbarium of Iraq Natural History Museum to be an important scientific reference for all researchers inside and outside the country. With the identification of botanical scientists for each family, gender and year in which it was first diagnosed.

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Publication Date
Tue Jan 31 2023
Journal Name
Iraqi Geological Journal
Reservoir Characterization and Rock Typing of Carbonate Reservoir in the Southeast of Iraq
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Flow unit and reservoir rock type identification in carbonates are difficult due to the intricacy of pore networks caused by facies changes and diagenetic processes. On the other hand, these classifications of rock type are necessary for understanding a reservoir and predicting its production performance in the face of any activity. The current study focuses on rock type and flow unit classification for the Mishrif reservoir in Iraq's southeast and the study is based on data from five wells that penetrate it. Integration of several methods was used to determine the flow unit based on well log interpretation and petrophysical properties. The flow units were identified using the Quality Index of Rock and the Indicator of Flow Zone. Th

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Publication Date
Sun Jun 02 2024
Journal Name
Journal Of Communicable Diseases
Evaluation of Susceptibility of Candida species to Six Antifungal Drugs in Iraqi Specimens
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Introduction: Candida spp. has become increasingly resistant to antifungal drugs, with elevated MIC levels causing a negative medical impact and increasing the number of patients at risk of candidiasis. According to the CDC, about 7% of Candida blood samples show reduced susceptibility to fluconazole. Monitoring the antifungal resistance profile of Candida spp. is vital, as non-Albicans species may limit treatment options. Objective: Evaluate the antifungal effectiveness against clinical Candida spp. isolates of six antifungals: amphotericin B, fluconazole, voriconazole, itraconazole, caspofungin, and 5-fluorocytosine. Methods: 100 samples were collected from various clinical samples at the National Centre of Teaching Laboratories

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Publication Date
Thu Sep 15 2022
Journal Name
Journal Of Baghdad College Of Dentistry
Determination of Surface Roughness and Accuracy of Alginate Impression Material Disinfected by Immersion
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Background: This study was conducted to evaluate the surface roughness and dimensional accuracy of commercially obtainable alginate impression material in terms of imbibition after immersion in two different media. Materials and method: Two disinfecting agents, ethanol 70% and povidone-iodine 4%, were used to access the dimensional accuracy and surface roughness of alginate impression material. Weights of specimen discs of alginate impressions were measured before and immediately after immersion to gain a measure of imbibition. For surface roughness, disinfected specimens rectangle was examined before and after disinfection. Results: Minimal changes in weight were observed after disinfection, but a statistically non-significant differenc

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