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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
Tue Jun 30 2015
Journal Name
College Of Islamic Sciences
The effect of negation in proving the pathology of the fundamentalists
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This research deals with the study of pathways in terms of the negative effect in proving them
And the fact of this influence among fundamentalists.
The research consists of two subjects and a conclusion.
In the first section, I learned about the terms in the title of the research:
Denial and pathology.
In the second section I reviewed the pathways of illness that affect exile in it
Five: the nodding, the fitting, the sounding, the division, the rotation, the inference
A description of the absence of evidence of non-reference to it. And I figured out how
Negation in it by striking some illustrative examples as fruit
Arising from the effect of negation in proving those routes.
As a result of this research, a

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Publication Date
Fri Feb 08 2019
Journal Name
Journal Of The College Of Education For Women
Effect of mother in development of nutritional education for her children
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Reprehensible during the period of human life ,particular in child hood and after weaning
baby,analmeating habits have acquired his remaining life time and here high Iights,the role of
the mother in the childs education,dietar habits, and health methods and what is beneficial to
his health and in sufficien quantities for the baby .brooze trails are learned by the childin the
home with animportant and significant role in the future,inacht.aaralgame course wisely,after
becoming more in dependent in its delision-making an choices beyond the control of parents.
The present study aimed to message measure the awareness of food the mother and her role in
the development of food awareness sons, and its relation ship with som

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Publication Date
Mon Aug 19 2024
Journal Name
Al-rafidain Journal Of Medical Sciences ( Issn 2789-3219 )
Psychosexual Implications of Tubal Ligation in a Sample of Iraqi Women
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Background: Tubal ligation, recognized as a surgical intervention that ensures permanent contraception, has established itself as an option for women seeking a definitive solution for family planning. Objective: To assess the psychosexual implications of tubal ligation in a sample of women in Baghdad, Iraq. Methods: A prospective cohort study was conducted in a teaching hospital for 2 years, from the first of January 2022 to the end of December 2023, in which 203 women who underwent tubal ligation were included. Results: In the present study, we found that 158 (77.8%) had no depression, mild depression presented in 27 (13.3%), and moderate depression in only 15 (7.4%). While 163 (80.3%) of women did not suffer from anxiety, 32 (15.8

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Publication Date
Tue Dec 30 2008
Journal Name
Al-kindy College Medical Journal
Evaluation of the Potential Role of Serum Selenium in Diabetic Patients
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Background: The altered status of some essential trace elements observed in diabetes could have deleterious influences on the health of the diabetics. Objectives: To estimate and study the potential role of serum Selenium in type 1, type 2 diabetics and healthy subjects; and its relation with lipid profile and glycemic index. Methods: A case control designed study was carried out at the National Diabetes Center (NDC) / Al-Mustansiria University; on a total of 94 participants formed of 32 type 1 diabetics, 32 type 2 diabetics and 30 healthy control participants. Data collected about age, sex and BMI; also, blood samples examined for FPG, HbA1C, serum total cholesterol, HDL cholesterol, non-HDL cholesterol, serum triglyceride and sera were

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Publication Date
Mon Jan 01 2018
Journal Name
Ultramicroscopy
Characterization of trapped charges distribution in terms of mirror plot curve
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Publication Date
Fri Oct 12 2018
Journal Name
International Journal Of Medical Research & Health Sciences
A Comparison of Fear Levels of Endodontic Treatment in Iraqi Population
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Introduction: Dental fear is defined as the patient’s specific reaction towards stress related to dental treatment in which the stimulus is unkn..

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Publication Date
Sun Dec 06 2009
Journal Name
Baghdad Science Journal
Effect the combination of antibiotics on clinical isolates of Staphylococcus aureus
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Atotal of 75 different clinical samples were collected from different hospitals in Baghdad Biochemical and morphological characterization tests showed that forty isolates were identified as Staphylococcus aureus Antibiotic susceptibility tests of all isolates towards ten antibiotics were carried out and results showed that many isolates (97.5 %) were resistant to ?-lactam antibiotic , 70 % were resistant to Tetracyclinee , 62.5% were resistant to co-trimoxazole , 60 % were resistant to ciprofloxacin , 55% were resistant both of chloramphenicol and erythromycin , 52.5% were resistant to gentamicin , 35% were resistant to rifampicin , 10% were resistant to vancomycin . According to the above results the S.aureus I1 which is isolated

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Publication Date
Sun Sep 21 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of the esthetic smile in a sample of Iraqi population
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Background: The aim of the present study is to evaluate the esthetic smile in sample of Iraqi adults and to assess the gender differences. Materials and Methods: 100 persons (50malesand 50 females had class I normal dental and skeletal selected for this study.Clinical examination and digital photograph with posed smile were performed for each individual. Six linear soft tissue parameters in each photograph using AutoCAD program 2011. Five visual and four quantitative evaluations of the smile were studied for eachsubject. The smile arch and index, buccal corridor spaces (BCSs) were studied.Descriptive statistics of the measurements were calculated. Independent student’s ttestswere used to evaluate the gender differences. Statistics: Desc

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Publication Date
Wed Apr 01 2020
Journal Name
Technology Reports Of Kansai University
Lascoux Resolution of Weyl Module in the Case of Partition (5,4,4)
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Publication Date
Wed Jan 01 2020
Journal Name
2nd International Conference On Materials Engineering & Science (iconmeas 2019)
New application of pervaporation to enhance the conversion of consecutive reaction
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This study investigates consecutive reaction assisted by pervaporation for the first time. It studies the saponification of diethyladipate DA with sodium hydroxide NaOH solution synchronous with separating ethanol from the reaction mixture through an aqueous – organic membrane. The effect of time on some variables such as: permeated ethanol concentration EtOH wt%, separation factor (α), concentration of NaOH solution CB in the reaction medium and the conversion of DA to monoethyladipate (the intermediate product) was studied. It was shown that EtOH wt% and the conversion increased with increasing time unlike CB but (α) showed the existence of maximum value during the time of experiment. The process of reaction assisted by pervaporation

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