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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 Jun 01 2016
Journal Name
Arabian Journal Of Geosciences
Geochemistry and petrology of Late Miocene-Pleistocene Dibdibba sandstone formation in south and central Iraq: implications for provenance and depositional setting
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Sat Jun 01 2013
Journal Name
Journal Of The College Of Languages (jcl)
The Intellectual as an Alien: A Study of Henry James's The Beast in the Jungle and James Joyce's "A Painful Case"
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This research paper studies the alienation of the intellectuals in the modern novel through the study of two alienated characters, John Marcher in Henry James's The Beast in the Jungle, and Mr. Duffy in James's Joyce's "A Painful Case." As a result of the complexity of life in the industrial societies, the individuals, especially the intellectual ones, feel themselves unable to integrate into social life; they fear society and feel that it endangers their individuality and independence. Thus, these characters live on the fringe of the societ

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Publication Date
Mon Jul 01 2024
Journal Name
Journal Of The Faculty Of Medicine Baghdad
The Burden of Chronic Obstructive Pulmonary Disease COPD in Stable Patients and its Association with Inflammatory Biomarkers and Body Mass Index
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Background: Chronic obstructive pulmonary disease (COPD) is a progressive airflow limitation that is preventable but not curable. It is associated with persistent symptoms that cause a considerable burden on individual productivity at work, and daily activities, and reduced quality of life, also burdening the healthcare system and society. Objectives: The study aims to measure the burden of COPD on patients in terms of daily activities and work productivity. It also seeks to investigate some inflammatory biomarkers' levels and their correlation with selected outcomes. Patients and Methods: A cross-sectional study on 120 stable COPD patients who were diagnosed and treated according to the GOLD guidelines at Kirkuk General Hospital's

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Publication Date
Wed Jan 29 2020
Journal Name
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Neutrophil/lymphocyte and platelet/lymphocyte ratios as potential markers of disease activity in patients with Ankylosing spondylitis: a case-control study
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The neutrophil/ lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) have the potential to be inflammatory markers that reflect the activity of many inflammatory diseases. The aim of this study was to evaluate the NLR and PLR as potential markers of disease activity in patients with ankylosing spondylitis.

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The study involved 132 patients with ankylosing spondylitis and 81 healthy controls matched in terms of age and gender. Their sociodemographic data, disease activity scores using the Bath Ankylosing

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Publication Date
Tue Dec 01 2020
Journal Name
Journal Of Economics And Administrative Sciences
The effect of the Iraqi dinar exchange rate on inflation and economic growth using the joint integration methodology "a standard study"
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The exchange rate is of great importance at the global and local levels alike, as this importance increases with the increasing rates of development of economic relations between countries of the world due to openness and integration into the global economy, expressed by the expansion of the volume of trade and financial relations between countries. The Central Bank of Iraq has set the need to stabilize this price as a goal to reduce inflation rates and reduce them to the internationally accepted rates by using the foreign currency sale window to achieve a balance between the forces of supply and demand for foreign currency and to preserve the value of the Iraqi dinar. The research concluded that the central bank was It has a maj

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Publication Date
Mon Dec 28 2020
Journal Name
Journal Of The College Of Education For Women
Expressing the Bewilderment of the Modern Man through Silence in Samuel Beckett’s Happy Days: بسعاد ماهر محيل, ومنذر عبد الرزاق سبع
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Samuel Beckett’s Happy Days (1961) clearly portrays a lack of communication among the characters of the play which refers to the condition of modern man. This failure of communication led Samuel Beckett to use a lot of pauses and silences in all plays written instead of using words. To express the bewilderment of the modern man during the 20th century, Beckett adopts the use of no language strategy in the dramatic works. After World War II, people were without hope, religion, food, jobs, homes, or even countries. Beckett gave them a voice. He used a dramatic language out of everyday things, in which silence was part of the syntax as a poetic repetition. Language is no more important to the modern man; instead, he us

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Publication Date
Thu Jun 15 2017
Journal Name
Journal Of Baghdad College Of Dentistry
Mechanical evaluation of nano hydroxyapatite, chitosan and collagen composite coating compared with nano hydroxyapatite coating on commercially pure titanium dental implant
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Background: Dental implants act as infrastructure for fixed restoration to look like as a natural tooth. Osseointegration is a biological events and considered as a base for success of dental implant. The aim of this study is to evaluate the bond strength between bone and Ti implant coated with mixture of nano hydroxyapatite-chitosan-collagen compared with Ti implants coated with nano hydroxyapatite implanted in rabbit tibia, after different period of implantation time (two and six weeks) by torque removal test. Material and methods: 36 screws of commercially pure titanium; 8mm in length and 3mm diameter , 18 screws coated with mixture of nano hydroxyapatite-chitosan-collagen and18 screws coated with nano hydroxyapatite by dip coating. St

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Publication Date
Sat Nov 30 2024
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Random amplified polymorphic DNA-based polymerase chain reaction is an effective tool to examine the genotoxic effects of some food colors
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A large number of natural or synthetic dyes have been removed from both national and international lists of permitted food colors because of their mutagenic or carcinogenic activity. Therefore, this study aimed to use the Random Amplified Polymorphic DNA-Based Polymerase Chain Reaction (RAPD-PCR) assay as a feasible method to evaluate the ability of some food colors as genotoxin-induced DNA damage and mutations. Lactiplantibacillus plantarum was used as a bioindicator to determine the genotoxic effects by RAPD-PCR using M13 primer after treatment with some synthetic dyes currently used as food color additives, including Sunset Yellow, Carmoisine, and Tartrazine. Besides qualitative analysis, the bioinformatic GelJ software was used for clus

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Publication Date
Fri Mar 01 2019
Journal Name
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Studying the Effect of Adding Doekhla kaolin Clay and Alumina to Iraqi Bauxite on Some Physical and Mechanical and Thermal Properties
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The aim of this work is to produce samples from Iraqi raw materials like Husyniat Bauxite (raw and burnt) and to study the effect of some additives like white Doekhla kaolin clays and alumina on that material properties were using sodium silica as a binding material. Five mixtures were prepared from Bauxite (raw and burnt) and kaolin clays, with an additive of (40) ml from sodium silica and alumina of (2.5, 5, 7.5,10 wt %) percentage as a binding material. the size grading was through sieving. The formation of all specimens was conducted by a measured gradually semi-dry pressing method under a compression force of (10) Tons and humidity ratio ranging from (5-10) % from mixture weight. Drying all specimens was done and then they were burn

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Publication Date
Mon Mar 07 2022
Journal Name
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The Effect of Teaching According to the Augmented Reality Technique on theVisual Thinking Skills to Scientific Fifth-Grade Students for Biology
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The research aims to identify the effect of teaching according to the augmented reality on the technique of the visual thinking skills among scientific fifth-grade students in a biology course. In order to achieve the goal of the research, the researcher adopted the experimental approach with the partial set of the two equal groups with the dimensional test of visual thinking skills, The research population represented all the scientific students of the fifth grade for morning government schools affiliated to the General Directorate of Education of Baghdad / Karkh II, alshakerin preparatory for boys was chosen intentionally, in which two groups were chosen for this study, one group is chosen randomly as the control group via lottery, whe

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