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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 Mar 10 2021
Journal Name
Baghdad Science Journal
Role of peptidoglycan in the pathogenesis of Staphylococcus saprophyticus in mice
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The pathogenicity of S. saprophyticus was studied in mice. A group of white mice were injected transurethrally using a catheter with S. saprophyticus S67 cell suspension in a concentration reached 109 CFU/ml. concomitantly, the role of its peptidoglycan in the pathogenicity was studied by injecting another group of mice with 0.3 mg/0.2 ml of partially purified S. saprophyticus S67 peptidoglycan extract. After autopsy, kidneys and urinary bladder showed several histopathological changes both in cells and peptidoglycan injected mice, included: hydropic degeneration, glomerulus shrinkage, congestion of renal vessels, infiltration of inflammatory cells, and dekeratinization in urinary bladder.

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Publication Date
Mon Jul 01 2019
Journal Name
International Journal Of Pharmaceutical Research
Distribution of pslA among Local Isolates of Biofilm- Producing Pseudomonas aeruginosa
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16S rRNA gene sequence examination is an effective instrument for characterization of new pathogens in clinical specimens. Akey component of colonization, biofilm formation, and protection of the pragmatic human pathogen Pseudomonasaeruginosais the biosynthesis of the exopolysaccharide Psl.Extracellular polysaccharides,biofilm, are secreted by microorganisms into the neighboring environment and are significant for surface attachment and keeping structural safety within biofilms.Biofilm production is an important technique for the survival of P. aeruginosa,and its association with antimicrobial resistance represents a defy for patient therapeutics. The aim of the current research is to assess the antibiotic resistance manner and distribution

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Publication Date
Wed Oct 24 2018
Journal Name
Chalcogenide Letters
STUDY OF GEOMETRICAL AND ELECTRONIC PROPERTIES OF ZnS WURTZOIDS VIA DFT
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Publication Date
Fri Dec 15 2023
Journal Name
Muthanna Journal For Agricultural Sciences
Evaluating of Different Types of Agricultural Nozzles Locally Used in Iraq
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The experiment aimed to Manufacture a device for checking the nozzles and testing its efficiency and to study the effect of research factors on the studied traits. The device was manufactured locally through using materials available in the Iraqi market. The system is Both Hydraulic and electronic (ISO 5682-1)1 relay on sensors technology and the test platform was built and designed on a movable trolly at the department of Agricultural Machines and Equipment / College of Agricultural Science / University of Baghdad. The design includes the use of mechanical water pump and electrical AC water pump. The design includes a nozzle holder that can accommodate three nozzles per test. The design also consists of spreading wings and stationa

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Publication Date
Wed Jan 01 2020
Journal Name
Medical Journal Of Babylon
Diagnostic value of neutrophil lymphocyte ratio in detection of acute appendicitis
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The diagnosis of acute appendicitis (AA) sometimes is illusive and the accompanying clinical and laboratory manifestations cannot be used for definitive diagnosis. Objective: This study aimed to evaluate the diagnostic value of neutrophil/lymphocyte ratio (NLR) in detection of AA. Materials and Methods: This is a cross-sectional study that included a total of 80 adult patients with AA and 62 age- and gender-matched patients with abdominal pain due to causes other than AA. Three milliliter of peripheral blood were collected from each participant. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. Receiver operating characteristic curve was used to assess the diagnostic value of NLR in detection

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Publication Date
Wed Feb 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
The Reflection Of The Financial Reporting Of Intellectual Capital Investment Decisions
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Abstract

The intellectual capital an important variable in the equation of the success of seeking economic units to achieve a competitive advantage, since it is a real capital for economic unity it constitutes a strategic importance as the main source to achieve high profitability in the economic unit and highlights the importance of showing intellectual capital components of the main Represent of human capital and structural capital and relational capital, through effective and the prominent role played by intellectual capital within the economic unity in order to achieve a sustainable competitive advantage contribute to attracting investors with longer investment decision of the most important and difficult decisions ta

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Publication Date
Fri Jun 30 2023
Journal Name
College Of Islamic Sciences
Moderation between the anvil of application and the hammer of extremism
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This research study focuses on fundamental questions. It deals with the content of the critical reviews through which the most important sources that undermine the renaissance of the Islamic human society can be concluded. It is the vague fetishization of the sacred between religion, politics, and ideas, which members of society live in  and which raised the dust of closed-minded fanaticism that led to the return of deviant extremism. It is oppression, violence, and domination, all of which are professional tools in the manufacture of the ideology of extremism in all its forms. Here,  the idea matured in giving a human, intellectual and philosophical overview that mixed the required drawing in the formulation of scientific cont

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Publication Date
Sat Oct 01 2016
Journal Name
World Journal Of Pharmaceutical Research
TERATOGENIC EFFECT OF METHOTREXATE ON HISTOGENESIS OF TESTIS IN NEWBORN RAT
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Background: Methotrexate (MTX) was one of the first drugs synthesized for a specific chemotherapeutic purpose used to inhibit folic acid (FA) for the treatment of acute lymphoblastic leukemia in children. Its history is closely related to the discovery and characterization of folic acid. It is used clinically in medicine to treat a range of cancerous and noncancerous conditions. MTX is currently used in gynecology to treat disorders arising from trophoblastic tissue, namely, ectopic pregnancy. MTX, the most frequently used diseasemodifying anti-rheumatic drug (DMARD), suppresses disease activity and reduces joint damage. The aim of study: It is designed to demonstrate the effect of MTX (7.5 mg/wk.) on the histogenesis of gonad (testis) of n

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Publication Date
Wed Jun 27 2018
Journal Name
Journal Of The College Of Education For Women
Kinds of unknowns and government linkages -empirical study of the application
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It is no secret that the prophets speech is of great importance, as the second source of Islamic legislation after the Holy Quran, and as such we must reserve and verify the authenticity of the novel and the narrators seizure, and all the conditions laid down by the scholars.

The subject of our research here concerns part of this verification, which is the unknown, the subject of the unknown hadith is considered a matter of great interest by the modernists because it relates to the validity of the novel and the narrators, and the methods of the modernists varied in terms of the reasons for this weakness, the fool never entertained them by the reckless narrative.

I chose the subject of my research the types of Mahjail and

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Publication Date
Thu Jun 30 2022
Journal Name
Gsc Biological And Pharmaceutical Sciences
Revision of public health and clinical importance of amoebiasis in Iraq
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Amebiasis, related to the pathogenic parasite Entamoeba histolytica, is a prominent cause of diarrhea globally. Amebiasis is primarily a disease of impoverished communities in developing nations, although it has recently arisen as a significant infection among returning tourists and immigrants. Severe cases are linked to a high case fatality rate. Although polymerase chain reaction (PCR)-based diagnosis is becoming more widely available, it is still underutilized. Treatment with nitroimidazoles is now suggested, however novel parasite medication research is a top priority. To avoid problems, amebiasis should be considered before corticosteroid therapy. Because there is no effective vaccination, sanitation and availability to clean w

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