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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
Mon Jun 30 2014
Journal Name
Al-kindy College Medical Journal
Unstable Angina /Non ST Elevation Myocardial Infarction: Frequency of Conventional Risk Factors; TIMI Risk Score, and Their Impact On Angiographic Data
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Background: Appreciation of the crucial role of risk factors in the development of coronary artery disease (CAD) is one of the most significant advances in the understanding of this important disease. Extensive epidemiological research has established cigarette smoking, diabetes, hyperlipidemia, and hypertension as independent risk factors for CADObjective: To determine the prevalence of the 4 conventional risk factors(cigarette smoking, diabetes, hyperlipidemia, and hypertension) among patients with CAD and to determine the correlation of Thrombolysis in Myocardial Infarction (TIMI) risk score with the extent of coronary artery disease (CAD) in patients with unstable angina /non ST elevation myocardial infarction (UA/NSTEMI).Methods: We

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Publication Date
Sat Sep 30 2023
Journal Name
College Of Islamic Sciences
Poetics and its functions In the book of "The Magic and Poetry" by Lisan Al-Din Ibn Al-Khatib (776 AH
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This study deals with a prominent critical term - poetics - in critical studies as an area related to uncovering the laws of creative and aesthetic discourses (Preaching)، and the various functions that accompany it in literary texts. So، the study employs the pioneers' works of this theory specially the eastern theorists in making a parallel comparing study of the text book of " the Magic and Poetry” by Al-Lisan Al-Din bin Al-Khatib (776 AH). It displays the utility of the concept of poetics in the referred book pointing to the illumination of various functions that، in turn، reflected the

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Publication Date
Sat Mar 02 2019
Journal Name
World Heart Journal
The Effects of Chronic Cigarette Smoking on the Right Ventricular Functions in Healthy Young Male Subjects: A Speckle Tracking Echocardiographic Study
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Background: Chronic cigarette smoking is one of the major risk factors for coronary artery disease. However, it has additional cardiac adverse effects independent of coronary atherosclerosis. Patient and Methods: After informed consent and perm- ission from the review board of the hospital, 80 healthy subjects who were classified as smokers or non-smokers were included in the study. They were examined by standard echocardiography protocol which was followed by two-dimensional speckle tracking to assess the functions of the right ventricle. Results: The tricuspid annular plane systolic excursion (TAPSE) was significantly reduced in smokers as compared to non-smokers (P < 0.05). The tricuspid flow peak late diastolic velocity (A wave) was sig

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Publication Date
Fri Dec 02 2022
Journal Name
Nankai Business Review International
Evaluating the dimensions of strategic intent according to the Hamel and Prahalad model/a case study in Oil Projects SCOP Company
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Purpose

The purpose of this study is to examine the dimensions of strategic intent (SI; see Appendix 1) according to the Hamel and Prahalad model as a building for the future, relying on today’s knowledge-based and proactive strategic directions of management as long-term and deep-perspective creative directions, objective vision and rational analysis, integrative in work, survival structure and comprehensiveness in perception.

Design/methodology/approach

The quantitative approach was used based on research, detection and proof, as data were collected from leader

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Publication Date
Mon Oct 02 2023
Journal Name
Journal Of Engineering
Controlling the Unbalanced Voltages of a Series-Connected Lead-Acid Batteries in a PV Power Storage System using Dynamic Capacitor Technique
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Lead-acid batteries have been used increasingly in recent years in solar power systems, especially in homes and small businesses, due to their cheapness and advanced development in manufacturing them. However, these batteries have low voltages and low capacities, to increase voltage and capacities, they need to be connected in series and parallel. Whether they are connected in series or parallel, their voltages and capacities must be equal otherwise the quality of service will be degraded. The fact that these different voltages are inherent in their manufacturing, but these unbalanced voltages can be controlled. Using a switched capacitor is a method that was used in many methods for balancing voltages, but their respons

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Publication Date
Sat Apr 01 2023
Journal Name
Baghdad Science Journal
Synthesis, Spectroscopy of New Lanthanide Complexes with Schiff Base Derived From (4-Antipyrinecarboxaldehyde with Ethylene Di-Amine) and Study the Bioactivity
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The study involved preparing a new compound by combining Schiff bases generated from compounds for antipyrine, including lanthanide ions (lanthanum, neodymium, erbium, gadolinium, and dysprosium). The preparation of the ligand from condensation reactions (4-antipyrinecarboxaldehyde with ethylene di-amine) at room temperature, and was characterization using spectroscopic and analytical studies ( FT-IR, UV-visible spectra, 1H-NMR, mass spectrometry, (C.H.N.O), thermogravimetric analysis (TGA), in addition to the magnetic susceptibility and conductivity measurement of the synthesis complexes, among the results we obtained from the tests, we showed that the ligand behaves with the (triple Valence) lanthanide ions, the multidentate

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Publication Date
Sun Dec 01 2013
Journal Name
Baghdad Science Journal
Theoretical Study of Charge Transfer in Styryl Thiazilo Quinoxaline Dyes STQ-1, STQ-2,and STQ-3 in Organic Media System
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Charge transfer in styryl dyes STQ-1, STQ-2,and STQ-3 with organic media system has been studied theoretically depending on the Franck- Condon rule and continuum dielectric model . The reorientation energies (eV) were evaluated theoretically depending on dipole momentum, dielectric constant , and refrective index n. The rate constant of charge transfer has been calculated depending on the reorientation energy (eV) ,effective free energy , potential height barrier , and coupling coefficient . A matlap program has been written to calculated the rate constant of charge transfer and other parameter. The results of calculations show that STQ-2 dye is more reaction for charge transfer compare with STQ-1 and STQ-3 dyes

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Publication Date
Thu Feb 01 2024
Journal Name
Journal Of Orthodontic Science
Presurgical management trends and nasoalveolar molding usage for infants with cleft lip and palate in the capital of a developing country
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BACKGROUNDS Nasoalveolar molding (NAM) application is among presurgical management (PSM) techniques used for infants with cleft lip and palate (CLP). It helps to approximate the palatal cleft and to reshape the nasoalveolar complex prior to primary lip repair. This study aimed to explore types of PSM and the dental speciality provision for infants with CLP in Baghdad. The status of NAM usage and surgeons’ perceptions toward NAM usage were assessed. MATERIALS AND METHODS This is a cross-sectional paper-based questionnaire study that collected responses of surgeons perform primary lip and nose repair regarding PSM. The questionnaire was distributed amongst public and private hospitals in Baghdad. Twenty surgeons were enrolled (only those su

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Publication Date
Wed Feb 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
A comparison between the logistic regression model and Linear Discriminant analysis using Principal Component unemployment data for the province of Baghdad
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     The objective of the study is to demonstrate the predictive ability is better between the logistic regression model and Linear Discriminant function using the original data first and then the Home vehicles to reduce the dimensions of the variables for data and socio-economic survey of the family to the province of Baghdad in 2012 and included a sample of 615 observation with 13 variable, 12 of them is an explanatory variable and the depended variable is number of workers and the unemployed.

     Was conducted to compare the two methods above and it became clear by comparing the  logistic regression model best of a Linear Discriminant  function written

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Publication Date
Fri Apr 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
Product development For Use Some Of The Lean Production Tools A Practical Research in the General Company for the automotive industry
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Abstract 

     This research aims to analyze the reality of the production process in an assembly line Cars (RUNNA) in the public company for the automotive industry / Alexandria through the use of some Lean production tools, and data were collected through permanence in the company to identify the problems of the line in order to find appropriate to adopt some Lean production tools solutions, and results showed the presence of Lead time in some stations, which is reflected on the customer's waiting time to get the car, as well as some of the problems existing in the car produced such as high temperature of the car, as the company does not take into account customer preferences,

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