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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
Fri Apr 29 2022
Journal Name
Iraqi Journal Of Agricultural Sciences
STABL ISOTOPES AND HYDROCHEMICAL PARAMETER AS INDICATORS OF AL-RAZZAZA LAKE WATER INTERACTION WITH GROUNDWATER SURROUNDING / KARBALA GOVERNORATE- IRAQ.
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This research was aimed to study the exposure of Razzazah Lake  to major hydrological changes in recent years as a result of natural climatic changes  and  drought, high evaporation in lake due to stop discharge from Habbaniyah Lake  by Al- majera channel. During 2019, we collected surface water samples at three locations, and three samples from groundwater, in addition one samples from each location Imam Ali Drop and Sewage water  of Karbala. The Results  show that the heavy isotopes in lake and groundwater well are enriched during the warm period, and depleted during the cold period. Chemically, The dominant cations and anions in Al-Razzaza lake water are mainly of in Order  Ca > Na > Mg and  Cl>SO4 and the water

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Thu Jan 23 2014
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Synthesis of Tetra Dentate N2O2 and their Complexes With Cu[II), Zn[II), Cd[II) and Hg[II) Ions
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Sat Jan 13 2018
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Zn(II) Removal from Wastewater by Electrocoagulation/Flotation Method using New Configuration of a Split-Plate Airlift Electrochemical Reactor
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Publication Date
Mon Feb 02 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Salivary C- reactive protein in relation to periodontal health among a group of patients with rheumatoid arthritis in Iraq
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Background: Rheumatoid arthritis is a chronic destructive inflammatory disease associated with destruction of joint connective tissues and bones, affecting 0.5%–1% of the population worldwide reporting higher prevalence of periodontitis among rheumatoid arthritis patients. The purpose of this study is to estimate level of salivary C-reactive protein in relation to the occurrence and severity of the periodontal disease and other oral parameters among group of patients with rheumatoid arthritis Material and methods: Fifty women patients with rheumatoid arthritis; twenty five on Methotrexate treatment and twenty five on combination treatment of Methotrexate and Etanercept selected as study groups with an age range (30-40) years old and

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Publication Date
Wed Aug 07 2019
Journal Name
Iraqi National Journal Of Nursing Specialties
Quality of Life for Adult Clients with Hypermobility Syndrome Attending Private Clinics in Baghdad City: A Cross-Sectional Study
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Publication Date
Mon Feb 02 2026
Journal Name
Al–bahith Al–a'alami
Petra University’s Students’ Uses For SMS Messages and its Verifications (A Field Study on Students of Petra University’s Colleges)
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Publication Date
Wed Oct 10 2018
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Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
THE STATUS AND CONSERVATION OF THE VULNERABLE MARBLED TEAL MARMARONETTA ANGUSTIROSTRIS, MENETRIS (AVES-ANSERIFORMES) IN AL-DALMAJ WETLANDS, IRAQ.
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    This study is considered the first effort of its kind in Iraq and in the Middle East towards studying the Marbled Teal Marmaronetta angustirostris that was carried on in Hor Al-Dalmaj, southern Iraq. The findings of this effort illustrate its importance as it paves the way for further study and observation for the bird and this important wetland itself. This study tackles the all possible aspects of the ecological and biological statuses of Marbled Teal (Threatened –Vulnerable bird species – IUCN Redlist) by means of field surveys and systematic monitoring that were conducted along the four seasons over the years 2013-2014 in one of the ecologically important and prominent and poorly-known wetlands in the

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Publication Date
Wed Dec 30 2020
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Modern Sport
The effect of special exercises using rubber ropes to develop special endurance and achieve a 200-meter freestyle swimming
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Swimming has now become the focus of attention of specialists, which has led to the search for the best methods and various methods of training, which rely heavily on scientific research and studies, through the use of proper planning and a comprehensive scientific and practical vision in the preparation and training process for this game. Some studies have proven that  The use of training methods has a positive role in the athletic training of the swimmer, provided that these methods are used in the correct way according to the scientific principles of training and with the loads and stresses that serve the specialized activity, i.e. the swimming distance. The study aimed at the follow 1- Preparing exercises using elastic ro

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Publication Date
Tue Sep 01 2020
Journal Name
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Reconstruction of Three-Dimensional Object from Two-Dimensional Images by Utilizing Distance Regularized Level Algorithm and Mesh Object Generation
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Fri Aug 01 2014
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