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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 01 2015
Journal Name
Journal Of Economics And Administrative Sciences
Analysis of Robust Principal Components Depends on the some methods of Projection-Pursuit
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The analysis of the classic principal components are sensitive to the outliers where they are calculated from the characteristic values and characteristic vectors of correlation matrix or variance Non-Robust, which yields an incorrect results in the case of these data contains the outliers values. In order to treat this problem, we resort to use the robust methods where there are many robust methods Will be touched to some of them.

   The robust measurement estimators include the measurement of direct robust estimators for characteristic values by using characteristic vectors without relying on robust estimators for the   variance and covariance matrices. Also the analysis of the princ

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Publication Date
Sun Jun 06 2010
Journal Name
Baghdad Science Journal
Viscosity Behavior of Solutions of Some Potassium Salts in Dimethyl Sulphoxide –Water mixture
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يتضمن البحث دراسة لزوجة محاليل تحتوي على املاح كلوريد البوتاسيوم وبروميد البوتاسيوم في مزيج من الماء وداي مثيل سلفوكسايد 60% وزنا داي مثيل سلفوكسايد.وقد اجريت الدراسة بست درجات حرارية مختلفة ونوقشت امكانية في ضوء معادلة جونز- دول حيث اخذ بنظر الاعتبار الحجم الايوني والشحنة وشكل جزيئات المذاب.

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Publication Date
Sun Apr 02 2017
Journal Name
Journal Of Educational And Psychological Researches
IQ TEST STANDARDIZATION OF MARTEN LOTHER JOHAN WITH CHILDREEN OF THE SEVEN YEAR
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This study aimed to IQ test standardization of Marten Lother Johan which used with childreen of the tow  stage at primary schools who aged (7) years old in Baghdad (Resafaa and Kharh).

 The importance of this study are :

1-The  importance of childhood and its role to develop the personality.

2-The importance of this age as the child will exposure to different kind of official teaching .

3-The capability for early detection of special category for early intervention in order to provide the necessary care .

4-Using the current test could consider as a predictive tool to screen the intelligent children .

In order to achieve the study aim, the researcher had followed the

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Publication Date
Wed May 01 2019
Journal Name
Solid State Phenomena
Preparation and Study of the Mechanical Properties of Unsaturated Polyester Resin/Graphene Nanocomposite
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Nanocomposite was prepared using unsaturated polyester (UP) resin as a matrix and graphene nanoparticles as a reinforcement material in six percentage weights (0, 0.1, 0.2, 0.3, 1 and 1.5%). Mechanical, calorimetric and thermal studies were performed on the (UP) resin/graphene nanocomposite. All tests showed a clear improvement of all mechanical properties examined (hardness, flexural strength (F.S), impact strength (I.S) and tensile strength (T.S)) with increasing graphene percentage. In addition, the temperature of glass transition and thermal conductivity of this composite increased with increasing graphene content.

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Publication Date
Tue Apr 02 2024
Journal Name
Journal Of Engineering
The Effect of Nano-Hydrated Lime on the Durability of Warm Mix Asphalt
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Premature failure in asphalt concrete pavement has been the main concern for pavement construction companies and engineers in recent years because of the large rise in traffic volume and loads and the temperature extremes in the summer and winter. The use of modifiers in asphalt concrete mixtures has attracted much attention to increase the performance and lifespan of pavements. As nanotechnology developed, several researchers concentrated on how these materials can help increase pavement serviceability by minimizing rutting and moisture damage. This study evaluates the Hydrated Lime (HL) effect by two methods (wet and dry hydrated lime) on the durability of the warm mix asphalt. The first method, HL, has been supplemented to the as

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Publication Date
Sun Mar 31 2013
Journal Name
Inventi Impact: Artificial Intelligence
SIMULATION OF IDENTIFICATION AND CONTROL OF SCARA ROBOT USING MODIFIED RECURRENT NEURAL NETWORKS
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This paper presents a modified training method for Recurrent Neural Networks. This method depends on the Non linear Auto Regressive (NARX) model with Modified Wavelet Function as activation function (MSLOG) in the hidden layer. The modified model is known as Modified Recurrent Neural (MRN). It is used for identification Forward dynamics of four Degrees of Freedom (4-DOF) Selective Compliance Assembly Robot Arm (SCARA) manipulator robot. This model is also used in the design of Direct Inverse Control (DIC). This method is compared with Recurrent Neural Networks that used Sigmoid activation function (RS) in the hidden layer and Recurrent Neural Networks with Wavelet activation function (RW). Simulation results shows that the MRN model is bett

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Publication Date
Mon Feb 16 2026
Journal Name
Research Journal Of Pharmacy And Technology
Ex vivo study of anti-leishmanial activity of artemisinin against Leishmania tropica amastigote
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Leishmania parasites are the causative agent of leishmaniasis. Many studies are inspecting chemical drugs, including the use of miltefosine and amphotericin B, but curative values may be limited for these drugs with side effects due to the chemical origin, therefore, investigating less toxic therapies is essential. The aim of this study was to investigate the effectiveness of artemisinin on Iraqi strain of Leishmania tropica, by experimental macrophage ex vivo infection of amastigotes into mouse macrophage cell-line RAW264.7. Different concentrations (100, 200, 300, 400, 500)μM of artemisinin (ART) were screened to examine the susceptibility of L. tropica amastigotes to invade macrophage cell line along three times of follow up (24, 48 and

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Publication Date
Sat Apr 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
The Appropriateness Of The Iraqi Environment For Establishment Of Hedge Funds In Iraq
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المستخلص

يهدف البحث إلى وضع إطار معرفي ومفاهيمي شامل لموضوع البحث, واغناء القارئ والمستفيد بالمعلومات الوافية عنه وتقليص الفجوات المعرفية للمهتمين به وقياس مدى ما هو متوفر وغير متوفر من المتطلبات الأساسية والضرورية لإنشاء صناديق التحوط في البيئة العراقية, وتمثلت صناديق التحوط بالمتغير الرئيس للبحث اما المتغيرات الفرعية فشملت (المتطلبات المالية, المتطلبات البشرية, البيئة التشريعية, الب

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Publication Date
Sun Jul 12 2020
Journal Name
Baghdad Science Journal
Spectroscopy Characterization of Ethylene Vinyl Acetate Degradation by Different Kinds of Accelerated Aging
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            This paper presents a sight about the chemical structure deformation of poly (ethylene-co-vinyl acetate) (EVA) samples according to the change ratio of rate constant values. Spectroscopy kinetics fluorescence curves are fitted for two characteristic wavelength domains of fluorescent intensities. The short wavelengths (320-400 nm) domain show spectra overlapping, while at long wavelengths (400-800 nm) domain spectra are arranged in regular for each specific accelerated aging time. The ratio of kinetics rate constant at long wavelengths to kinetics rate constant of short wavelengths is the criterion of the degree chemical structure deformation. Molar extrin

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Publication Date
Wed Dec 13 2017
Journal Name
Al-khwarizmi Engineering Journal
Design and Simulation of L1-Adaptive Controller for Position Control of DC Servomotor
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This paper presents L1-adaptive controller for controlling uncertain parameters and time-varying unknown parameters to control the position of a DC servomotor. For the purpose of comparison, the effectiveness of L1-adaptive controller for position control of studied servomotor has been examined and compared with another adaptive controller; Model Reference Adaptive Controller (MRAC). Robustness of both L1-adaptive controller and model reference adaptive controller to different input reference signals and different structures of uncertainty were studied. Three different types of input signals are taken into account; ramp, step and sinusoidal. The L1-adaptive controller ensured uniformly bounded

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