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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 May 22 2024
Journal Name
Al-rafidain Journal Of Medical Sciences ( Issn 2789-3219 )
Assessment of Urine and Serum Exosomes as Biomarkers for the Diagnosis of Bladder Cancer
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Background: Bladder cancer (BC) is the most common malignant tumor in the urinary tract and the tenth most common malignancy worldwide. Exosomes are 40–100 nm-diameter nanovesicles that are either released straight from the plasma membrane during budding or merged with the plasma membrane by multivesicular bodies. Objectives: To assess the proportion of serum and urinary Exosome levels in urinary bladder cancer patients, as well as their impact on the disease. Methods: From January 2023 to June 2023, a total of 45 samples of blood and urine were collected from individuals diagnosed with bladder cancer at the Ghazi Hariri Hospital for Specialized Surgery. They included 45 male and female patients, varying in age, as well as 45 heal

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Publication Date
Wed Jan 01 2025
Journal Name
Journal Of Governance And Regulation
The impact of corporate governance and audit quality on value relevance of accounting information
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This study aims to investigate the relationship between corporate governance (CG) and audit quality (AQ) in the adequacy of the value relevance of accounting information (VRAI). The study sample included Iraqi firms listed on the Iraqi Stock Exchange (ISE) from 2010 to 2022. Nineteen firms were a research sample selected from 44 firms listed on the ISE. They chose to use the model (Ohlson, 1995) in measuring VRAI, which is based on measuring the absolute value of the level of value relevance to earnings per share (EPS) the absolute value of the book value suitability level VRAI. CG was measured through five factors: board size, gender of board members, independence of the board from the chief executive officer (CEO), ownership perce

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Publication Date
Fri Jan 01 2021
Journal Name
Family Medicine & Primary Care Review
Assessment of depressive symptoms among students at Al-Kindy College of Medicine in Baghdad
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Background Depression is one of the most common medical illnesses worldwide. Medical students during their training will be subjected to many stressors, both mentally and emotionally. Objectives Assess the prevalence of depressive symptoms among medical students and to identify any association between depressive symptoms and some socio-demographic factors.

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Publication Date
Tue Dec 31 2024
Journal Name
Journal Of The Faculty Of Medicine Baghdad
The Role of Microelements of Lumbar Disc Degeneration in Patients Undergoing Lumbar Spine Surgery
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Background: Lumbar disc degeneration (LDD) is a common musculoskeletal disorder that frequently causes low back pain (LBP). In addition to the discomfort of lower back pain, it can accompany pain in one or both legs. The lumbar spine and sacrum, consisting of five vertebrae and one bone, determine the spine's balance. Microelements are essential in bone metabolism and are associated with the prevention of osteoporosis and the alleviation of musculoskeletal pain. Objectives: To examine the correlation between lumbar spinal surgery and the concentrations of microelements, namely zinc and copper. Methods: A case-control study was conducted in Ghazi Al-Hariri Hospital in Baghdad, Iraq, during the period from October 2023 to January 2024

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Publication Date
Sun Nov 01 2020
Journal Name
Journal Of Engineering
Simulation of Pose to Pose Moving of the Mobile Robot with Specified GPS Points
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The applications of mobile robots in rescue scenarios, surviving to search, and exploration for outdoor navigation have received increasing attention due to their promising prospects. In this paper, a simulation of a differential wheeled mobile robot was presented, implementing a Global Positioning System (GPS) data points to specified starting points, final destination, and total error.

In this work, a simple kinematic controller for polar coordinate trajectory tracking is developed. The tracking between two points, pose to pose, was specified by using the GPS data points. After that, the geodesy (GEO) formulation was used to convert the geodesy coordinate to Euclidean or polar coordinate. The Haversine equation

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Publication Date
Thu Nov 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
Requirements of investment in the marsh : a case study in the Marshlands of Maysan
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The search aims to find out the most important requirements for the success of marshes investment and maximize the expected returns of investment was marked by a problem find aquestion for availability requirements necessary for the success of marshes investment has a research community owners decision in the province Maysan the most important conclusions to the search is that the investment great importance in support of the economy and raising the cultural and social level, there is no investment successful but only with configure the investment environment appropriate economic, social, cultural, political, and security ways. the most important recommendations are working on the provision of the investment environment appropria

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Publication Date
Thu Dec 30 2010
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
DETERMINATION OF THE OPTIMUM OPERATING CONDITIONS IN THE GRANULATION OF GAMMA ALUMINA CATALYST SUPPORT
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Granulation Technique for Gamma Alumina Catalyst Support was employed in inclined disk granulator (IDG), rotary drum granulator (RD) and extrusion – spheronization equipments .Product with wide size range can be produced with only few parameters like rpm of equipment, ratio of binder and angle of inclination. The investigation was conducted for determination the optimum operating conditions in the three above different granulation equipments.
Results reveal that the optimum operating conditions to get maximum granulation occurred at ( speed: 31rpm , Inclination:420 , binder ratio:225,300% ) for the IDG,( speed: 68rpm , Inclination: 12.50 , binder ratio: 300% ) for the RD and ( speed:1200rpm , time of rotation: 1-2min )for the Caleva

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Publication Date
Tue Aug 01 2023
Journal Name
Journal Of Ecological Engineering
Assessment of the Pressure Driven Membrane for the Potential Removal of Aniline from Wastewater
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Publication Date
Mon Oct 01 2018
Journal Name
Chemical Physics Letters
Effect of heat treatment on photoelectrochemical performance of hydrothermally synthesised Ag2S/ZnO nanorods arrays
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Publication Date
Sun Jan 01 2017
Journal Name
Aip Conference Proceedings
Localization and counting of CD68-labelled macrophages in placentas of normal and preeclamptic women
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