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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 2011
Journal Name
Journal Of Economics And Administrative Sciences
Methods of using the periodic chart in the case of the missing values of the stable AR model (2)
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In this study, we investigate the behavior of the estimated spectral density function of stationary time series in the case of missing values, which are generated by the second order Autoregressive (AR (2)) model, when the error term for the AR(2) model has many of continuous distributions. The Classical and Lomb periodograms used to study the behavior of the estimated spectral density function by using  the simulation.

 

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Publication Date
Tue Jun 01 2021
Journal Name
Arab Researcher
The Civil Liability of Hotels toward Victims of Sex Trafficking – A Study in Light of Iraqi and U.S. Law
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In view of the large profits made by the sex trade on the one hand, and the minor penalties imposed on the traffickers (brokers) compared with the severe penalties imposed on the drug trade and illegal weapons, on the other hand, this trade has become popular and spread in most countries of the world, and the cornerstones of this trade and A safe haven for them is hotels, especially luxury ones with international brands where their guests are rich and some may look for sex for money. Given the great physical and psychological damage to the victims, this research highlights the civil liability of hotels towards these victims in US and Iraqi law.In order not to limit the

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Publication Date
Tue Dec 11 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Impact of Different Degrees of Uterine Prolapse on Sexual Function of Women at Teaching Hospitals in Al-Hilla City
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Background: Women sexuality is basic right and it plays a major role in women's Health aspects. Up is one of the factors that lead to sexual dysfunction while the incidence of it is rising as UP severity being more. Objectives: To assess the impact of different degrees of uterine prolapse on sexual function of women at teaching hospitals in AL-Hilla City. Methodology: A descriptive analytical study was conducted from 1ST Feb to 10th Jun /2014 to assess the impact of different degrees of uterine prolapse on sexual function for women who attend to consultant clinic at teaching hospitals in AL-Hilla City

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Publication Date
Sat Feb 01 2020
Journal Name
Journal Of Economics And Administrative Sciences
Study Impact of Some Factors on Daily Number of Hours Providing of Electricity in Baghdad City Using Path Analysis
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دُرِست العوامل المؤثرة في عدد ساعات تجهيز الكهرباء في مدينة بغداد، وتكونت عينة الدراسة من (365) مشاهدة يومية لعام 2018، وتمثلت بستة متغيرات استعملت في الدراسة. كان الهدف الرئيس هو دراسة العلاقة بين هذه المتغيرات، وتقدير تأثيرات المتغيرات التنبؤية في المتغير التابع (عدد ساعات تجهيز الكهرباء في مدينة بغداد). ولتحقيق ذلك استعملت نمذجة المعادلات الهيكلية/ تحليل المسار وبرنامج AMOS

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Publication Date
Sun Feb 15 2026
Journal Name
Journal Of Physical Education
The reality of the heroic graduate students in the College of Physical Education and Sports Sciences, University of Baghdad
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Publication Date
Wed Mar 18 2020
Journal Name
Baghdad Science Journal
Effect of Temperature and Alcohol on the Determination of Critical Micelle Concentration of Non- Ionic Surfactants in Magnetic Water
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The determination of critical micelle concentration of selected non-ionic surfactants (Tween 20,40 and 80) have been investigated using magnetic water(MW)as an aqueous medium.Conductometry technique is used to determine critical micelle concentration.The effect of alcohol addition and temperature variation at the range(293.15 -303.15K) are also pursued. It is concluded that the process of micellization is spontaneous and endothermic because of the observed free energy of micellization (ΔGom) , enthalpy change of micellization  (ΔHom), and entropy change of micellization (ΔSom) for the system was also studied.The properties of the non-ionic surfactants were studied, both in absence and presence of

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Publication Date
Sun Mar 01 2020
Journal Name
Baghdad Science Journal
The Effect of Alcoholic and Aqueous Extract of Piper nigrum on the Larvae of Culex pipiens molestus Forskal (Diptera:Culicidae)
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          The present study includes the effect of the ethanolic and aqueous extract of Piper nigrum against the third instar of Culex pipiens molestus (Diptera:Culicidae) in different concentrations: 1, 1.5 ppm of ethanolic extracts of Piper nigrum causing 100% mortality of larvae in the second day of treatment, while the concentrations 5% of aqueous extracts of Piper nigrum caused 100% mortality of larvae in the second day of treatment. The concentration 2.5% caused 100% mortality of larvae after four days of treatment. The current study also detected the effect of 0.1% concentration of Piper nigrum aqueous extract. The effect of this concentratio

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Publication Date
Thu Dec 13 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Impact of Using Social Media upon the Mental Health of Adolescent Students of preparatory Schools in Al-Diwanyah City
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Objective: To know the impact of social networks on the mental health of adolescents in the city of Diwaniyah.
Methodology: A descriptive cross-sectional study was conducted on adolescents in preparatory schools in ALDiwaniyah
City Center, for the period from Jun 26, 2015 through to October 20, 2015. The schools were
selected from using Probability sampling (240 random samples) six schools were selected from 32 schools (20 %
from total number) the schools were chosen by writing the names of all schools on a pieces of paper and put in
bags. Then, selected six schools random, three boys schools (2 preparatory and 1 secondary) three girls schools
(2 preparatory and 1 secondary), then I chose the sample the students in grad

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Publication Date
Sun Feb 15 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Determination of the effect of stress on the salivary cortisol level among sample of university students having myofacial pain
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Background: Psychological stress is considered the major etiological factor precipitating myofacial pain and temporomandibular disorders.It is known that stress induce various adaptational responses of physiologic systems. The process includes increase in the activity of the hypothalamic-pituitary-adrenal axis which promotes cortisol secretion. Salivary cortisol has been used as a measure of free circulating cortisol levels.The use of salivary biomarkers has gained increased popularity since collecting samples is non-invasive and painless. The aim of thisstudy was to evaluate the level of cortisol in saliva among sample of university students having myofacial pain, during the final exam period and whether this finding could have a significa

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Publication Date
Mon Oct 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
Reflection of applying the requirement of IFRS 9 regards impairment of Banks loans on earning management in Iraqi Banks
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Impairment of financial assets defined according to IFRS 9 as the difference between all contractual cash flows that are due to an entity in accordance with the contract and all the cash flows that the entity expects to receive, the entity should estimates all the cash flows through looking to the contract terms during the life time period of the assets or for shorter period if possible, the cash flow should include the amounts of selling any collateral taken or any other enhancement. On the other hand, the Central bank of Iraq guidelines regards impairment differ from the IFRS 9 that’s does not consider the collateral value on calculating the impairment that’s effects on the net profit through recognizing exaggerated loss an

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