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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
Thu Sep 01 2011
Journal Name
Journal Of Economics And Administrative Sciences
The relationship between organizational justice and empowerment and their impact on achieving organizational commitment (field study in the Department of Labor and Vocational Training)
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The research has deal with the relationship between organizational justice and empowerment and their impact on the achievement of organizational commitment in the office of Labour and Vocational Training. To study the research problem which is represented a sense that employees with low levels of organizational justice and empowerment and the reflection on the organizational commitment of the employees, so that Has been collecting data and information relating to research by designing a questionnaire, were distributed to a sample of (50) people in the office mentioned, and the results of the study to confirm the research hypotheses. and the key results of the research was the presence of correlation relationships and the effect o

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Publication Date
Thu Oct 26 2023
Journal Name
Malaysian Journal Of Science
HEMICAL ELUCIDATION AND BIOLOGICAL SCREENING STUDY OF NEW LIGAND DERIVED FROM 5, 6-O-ISO PROPYLIDENE-L-ASCORBIC ACID AND ITS METAL (II) COMPLEXES
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Tue Jun 12 2018
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المجلة العراقية لبحوث السوق وحماية المستهلك
BIOLOGICAL ASPECTS AND PREDATORY EFFICIENY OF PREDATOR Chilocorus bipustulatus (L.) COLEOPTERA :COCCINELLIDAE ON DATE PALM SCALE Parlatoria blanchardi (T.) DIASPIDIDAE: HOMOPTERA UNDER LABORATORY CONDITIONS.
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Laboratory studies were conducted at the biological control unit, college of Agriculture, University of Baghdad to evaluate some biological aspects of the predator Chilocorus bipustulatus (Coleoptera: Coccinellidae), which is considered one of the most important predators on many insect pests, especially the scale insect, Parlatoria blanchardi, (Homoptera: Diaspididae) on date palms. The results showed that biological parameters of the predator were varied according to different degree of temperature. Egg incubation period was significantly different and reached to 7.5 and 5.44 day at 25 and 30°C respectively, Fertility was the same 100% at both temperature degrees. Larval growth periods were 17.41 and 16.12 day as well as the mortality du

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Fri Feb 13 2026
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Shear bond strength of different lingual buttons bonded to wet and dry enamel surfaces with resin modified glass ionomer cement (in vitro comparative study)
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Background: This study was aimed to investigate the effect of three lingual button (Nickel free / rectangular base, Nickel free / round base and Composite) and bonding environment, wet and dry enamel surface, on: the shear bond strength (SBS) of light and self-cured Resin Modified Glass Ionomer Cements, and the debonding failure sites. Materials and method: One hundred twenty no-carious, free of cracks maxillary first premolar teeth were selected. Three types of orthodontic lingual buttons were used in this study: Nickel free / rectangular base, Nickel free / round base and Composite buttons. The teeth were divided into two groups of sixty teeth each. One group was used for testing the chemically cured GC Fuji Ortho Resin modified Glass Io

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Publication Date
Thu Oct 01 2009
Journal Name
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Topical 10% lactic acid solution in the treatment of pityriasis versicolor in comparison with topical 1% clotrimazol solution (single-blind, comparative and therapeutic study)
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Sun Mar 07 2010
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The effect of aqueous extracts and isolation proteinous compound from clove buds on serumglucose, triglyceride , glutathione and malnodialdehyde levels in alloxan induced diabetic mice
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Sat Sep 30 2023
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Iraqi Geological Journal
Geology, Pb and S Isotope Geochemistry, and Genesis of the Na Bop-Pu Sap Lead-Zinc Deposit in the Cho Don area, Northeastern Vietnam
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The Na Bop-Pu Sap Pb-Zn ore bodies represent a typical vein-type lead-zinc deposit situated in the Cho Don area and are currently being extracted for their lead and zinc resources. This deposit is characterized by its significant scale and quality and is considered one of the prominent lead-zinc deposits in the Cho Don area. Despite its significance, this deposit has not received adequate attention, resulting in limited knowledge of its geology, mineralization, and deposit genesis model. To address this knowledge gap, our study utilized several methodologies, including field surveying, ore mineral analysis under a microscope, and S and Pb isotopic geochemistry. By employing these approaches, we were able to obtain specific insights

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The Effect of using 940 nm Diode Laser in Comparison with Endoactivator on Radicular Dentin Permeability and Smear Layer Removal (An in Vitro Study)
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Abstract: The aim of this study is to assess the effectiveness of 940 nm diode laser in comparison to Endoactivator in elimination of smear layer in terms of radicular dentin permeability and ultra-structural changes of root canal walls by SEM evaluation. Twenty-eight single-rooted extracted lower premolars were instrumented up to size X4 (protaper Next, Dentsaply) and divided into two experimental groups according to the irrigation system, G1; activated by EndoActivator and G2; activated by Diode laser 940 nm, CW mode, 1.7 W. Afterward, the roots were made externally impermeable, filled with 2%methylene blue dye, divided horizontally into three segments representing the apical, middle, and coronal thirds then examined under stereo- micr

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Publication Date
Fri Dec 01 2017
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Job enrichment, knowledge capital and its impact on strategic success: exploratory study at a sample of the Iraqi government and Private Colleges on Baghdad
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Correlation between Serum Levels of Factor I, CD59, Interferon-gamma, and Interleukin-6 with the Response to Rituximab in Iraqi Patients with Rheumatoid Arthritis
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Background: Rituximab is a chimeric IgG1 kappa immunoglobulin that has been genetically modified to incorporate human constant region sequences together with murine light- and heavy-chain variable region sequences. People use it to treat rheumatoid arthritis and certain malignancies. Objective: The study aimed to assess the potential association between the serum levels of Factor I, CD59, interleukins (IL)-6, and interferon-gamma (IFN)-γ and the response to Rituximab treatment in Iraqi rheumatoid arthritis patients. Methods: A cross-sectional study was conducted at the rheumatology center at Baghdad Teaching Hospital. Ninety adult patients who have been diagnosed with rheumatoid arthritis and are receiving  Rituximab intravenous i

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