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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 11 2019
Journal Name
Al-kindy College Medical Journal
Indications of Intravitreal Injection of Bevacizumab in a sample of Iraqi patients
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Background: Anti-vascular endothelial growth factors commonly used intravitreally for treatment of variable retinal disease worldwide, which help to regulate the upregulation of vascular endothelial growth factors due to ischemia or/and other retinal insult.

Objective: To review all cases of intravitreal bevacizumab given in the retinal unit of the Eye Specialty Private Hospital in Iraq from December 2015 to June 2016, pointing out the common indications.

Methods: A retrospective study including all cases of intravitreal injections of bevacizumab recorded at the Eye Specialty Private Hospital from December 2015 to June 2016 were retrieved. Age, sex, laterality, diagnosis

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Publication Date
Sat Sep 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of the efficacy of ultrasound in the diagnosis of cervical lymphadenopathy
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Background: Cervical lymph nodes are prone to involved by a number of pathologic processes. They are common sites for lymphoma, metastasis, and reactive enlargement in a number of conditions. Aims of the study:-Clinical evaluation of patients with cervical lymphadenopathy. Differentiation between benign and malignant lymph nodes by means of ultra sounds (US) and Correlate the US findings with cytological and/or histopathological findings of cervical lymph nodes. Subjects, Materials and Methods:-The present study was carried out over a period of 6 months and included 81 patients of different age groups presenting with cervical lymphadenopathy. Each patient was examined clinically, then comprehensive sonographic examination of the neck for

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Publication Date
Wed Mar 30 2016
Journal Name
College Of Islamic Sciences
Methods of Quran inference On the existence of the Creator of sleep
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The issue, the existence of God Almighty, and the creativity of the universes including the whale, and assets and how diversified, and faith in him and his lordship and divinity, is a delicate issue, and very important and dangerous, and it occupied human thought old and new, and still occupy it until God takes the land and on it. Many complex issues of thought, behavior, and ethics have resulted in the belief of many communities in the existence of the Almighty, having ruled their minds, depicting their beliefs and distancing their thoughts about slippage and abuse. When they looked at the wonders of creatures and the minutes of the assets, they thought about the planetary and astronomical motion systems. His existence was denied by ath

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Publication Date
Fri Nov 09 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Effects of Spontaneous Abortion on Women's Psychological Domain of Quality of Life
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Objective: To find out the association between psychological domain of Quality of life with study variable
(demographic &reproductive).
Methodology: A descriptive Analytical study was conduct on Non-probability (purposive sample)of (200) women
who have suffering from spontaneous abortion in maternity unit from four hospitals which include Al-Elwyia
maternity teaching hospital, and Baghdad teaching hospital at Al-Russafa sector. Al –karekh maternity hospital
and Al-Yarmook teaching hospital at Al-karekh sector. A questionnaire was used as a tool of data collection for the
period of February 3rd 2013 to April 26th 2013 and consisted of four parts, including demographic, reproductive
characteristics, and psycholog

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Publication Date
Sun Dec 01 2024
Journal Name
Научный Форум: филология, искусствоведение и культурология
Motivating signs of the concept of "Summer" in the linguoculture of Iraqis.
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Publication Date
Mon Apr 03 2023
Journal Name
Journal Of Genetic And Environmental Resources Conservation
Histopathological of effect of zinc on liver architecture of mice, Mus musculus
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The current study was conducted to find out the effect of zinc (Zn) on the liver tissue of adult male white mouse, Mus musculus at concentrations (50 and 100 mg/kg/day) and for (30) days.(30) mice were used, divided into three groups of (10) mice, represented by control group, group of (50) mg/kg/day and (100) mg/kg/day. Histopathological changes appeared in the liver of male mice treated with zinc in concentration (50 and 100 mg/kg/day) for 30 days, including deformation and damage to Glisson's capsule, epithelial separation of capsule, in addition to cellular changes represented by hypertrophy of hepatocytes, as seen a swelling necrosis, hypertrophy of nuclei, thickening and degeneration in some hepatocytes, as well as the observed scatte

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Publication Date
Mon Mar 11 2019
Journal Name
Baghdad Science Journal
Hydrochemistry of Groundwater in Northeast Part of Anbar Governorate – West of Iraq
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A groundwater quality assessment has been carried out in northeast part of Anbar governorate in western Iraq. We analyzed hydrochemical parameters such as pH, electrical conductivity, total dissolved solids presence of ions to describe groundwater quality. The study area has the only confined aquifer within the geological formation extended in area. Values of groundwater hydrochemical parameters were ranged from (7) to (7.9) for ph, (1599) to (6800) µmhos/cm for electrical conductivity (EC) and (1048) to (4446) mg/l for total dissolved solids (TDS). The origins and types of groundwater in the area were of marine origin and MgCl2 water type while only (6) samples were of continental origin and Na2SO4 wate

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Publication Date
Fri Jan 01 2016
Journal Name
European Journal Of Biology And Medical Science Research
Impact of an educational intervention of training of breast feeding promoting on the knowledge and attitude of a sample of mothers: a study of a pre and post evaluation.
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Background: Health professionals have a crucial role in promotion, support and management of breastfeeding. To be effective in this effort, the clinician should focus on the issue from the preconception stage through pregnancy and delivery, and continue in subsequent infant care. Aim of the study: to assess the effectiveness of the UNICEF/WHO 40-hour of breast feeding training through the assess breastfeeding knowledge and attitudes of the health profession staff before and after training course.

Publication Date
Sun Aug 17 2025
Journal Name
Al-fatih Journal
The impact of the use of some herbal sedative level of achievement in the development of air pistolEmpirical researchOn a sample of players Faculty of Physical Education for Girls
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تعد الرماية واحدة من الألعاب التي يقاس مستوى الانجاز فيها بالأرقام إذ ارتفعت الأرقام المسجلة بالنسبة لسلاح المسدس الهوائي حتى وصلت عند بعض الأبطال العالميين إلى الانجاز النهائي ، وقد لجأ المدربون إلى مختلف الطرق التدريبية, وان ضعف الثبات والتركيز هما اللذان يقودان إلى هبوط مستوى الانجاز في الرماية ، ولتحقيق التركيز والثبات المطلوبين أثناء الرمي يجب التدريب على مطاولة حمل السلاح التي تعد من أصعب تدريبات الر

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Publication Date
Thu Feb 24 2022
Journal Name
Journal Of Educational And Psychological Researches
Analytical Study of the Content of Social and National Studies Textbooks of the Middle Stage in Kingdom of Saudi Arabia in the Light of the Values of Social Peace
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This study aimed to reveal the extent to which the values of social peace are included in the content of social and national studies textbooks of the middle stage in kingdom of Saudi Arabia. To achieve this goal, the researcher used the descriptive analytical approach. The study sample consisted of all developed social and national studies textbooks of the middle stage in kingdom of Saudi Arabia in first and second semester of student books in edition of 1439-1440. The study tool was the analysis card. The study reached the following results: 1-The content of social and national studies textbooks of the middle stage in kingdom of Saudi Arabia as a whole included (38) social peace values of total (40) values, corresponding to the inclusio

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