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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
Sat Jan 01 2022
Journal Name
Open Engineering
Field tests of grouted ground anchors in the sandy soil of Najaf, Iraq
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Abstract<p>This article presents test results documentation for four grouted ground anchors embedded in sandy soil. Three anchors were trial, while one was a working anchor. One trial anchor is instrumented with eight resistance-type strain gauges glued on the corrugated pipe and embedded within the grouted body. An acceptance test was made for all anchors to determine the working load. Acceptance criteria suggested by the Post-Tensioning Institute were applied, and the working anchor did not pass the creep criterion, so it was taken out of service. The strain measurements indicated that the compression stresses were generated along the free length, while the tension stresses were generated alon</p> ... Show More
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Publication Date
Mon Mar 15 2021
Journal Name
Al-academy
Effect of formation Methods on Sintering Process of Ceramic Materials: هديل سلمان سعيد
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The current research is concerned with methods of formation and their effect on the sintering process of ceramic materials. The research is divided into a number of chapters. The first chapter addressed the research structure (the research problem, importance, objective, limits, and it also defined the terms used in the research). The second chapter addressed the theoretical framework, where the theoretical framework has been divided into three sections. The first section dealt with methods of formation of ceramic materials including: Plasticizing method 2- semi-dry pressing method 3- dry pressing method 4- extrusion method 5- casting method.
The researcher found that there is a clear difference between the methods through her formati

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Publication Date
Sat Dec 01 2012
Journal Name
Al Mustansiriyah Journal Of Pharmaceutical Sciences
Formulation and In Vitro Evaluation of Mucoadhesive Antimicrobial Vaginal Tablets of Ciprofloxacin Hydrochloride
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Ciprofloxacin is a broad spectrum fluoroquinolone, effective in the treatment of a wide range of infections, including genitourinary tract infections.In this study, bioadhesive vaginal tablets of ciprofloxacin hydrochloride were prepared by direct compression method using a combination of bioadhesivepolymers carbopol 934P(Cp), carboxymethylcellulose (CMC) and sodium alginate (SA) in different ratios.The prepared tablet formulations were characterized by measuring their swelling capacity, surface pH, bioadhesive properties, and in-vitro drug dissolution. It was found that the bioadhesive force was directly proportional to carbopol 934P content in different formulae and was further enhanced by the inclusion of carboxymethylcellulose.

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Publication Date
Mon Mar 01 2021
Journal Name
Astronomy Letters
The Dichotomy of the Mass-radius Relation and the Number of Globular Clusters
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Publication Date
Mon Aug 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
"Compared some of the semi-parametric methods in analysis of single index model "
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As the process of  estimate for model and variable selection significant is a crucial process in the semi-parametric modeling At the beginning of the modeling process often At there are many explanatory variables to Avoid the loss of any explanatory elements may be important as a result , the selection of significant variables become necessary , so the process of variable selection is not intended to simplifying  model complexity explanation , and also predicting. In this research was to use some of the semi-parametric methods (LASSO-MAVE , MAVE and The proposal method (Adaptive LASSO-MAVE) for variable selection and estimate semi-parametric single index model (SSIM) at the same time .

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Publication Date
Mon Oct 02 2023
Journal Name
Journal Of Engineering
Control of Propagation of Salt Wedge by using Roughness Blocks having Different Inclination
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The hydraulic conditions of a flow previously proved to be changed when placing large-scale geometric roughness elements on the bed of an open channel. These elements impose more resistance to the flow.  The geometry of the roughness elements, the numbers used, and the configuration are parameters that can affect the hydraulic flow characteristics. The target is to use inclined block elements to control the salt wedge propagation pointed in most estuaries to prevent its negative effects. The Computational Fluid Dynamics CFD Software was used to simulate the two-phase flow in an estuary model. In this model, the used block elements are 2 cm by 3 cm cross-sections with an inclined face in the flow direction, with a length

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Publication Date
Thu Oct 08 2020
Journal Name
Journal Of Legal Sciences
The Impact of the COVID-19 Pandemic on the Performance of Contractual Obligations
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The global health crisis resulting from the spread of the Corona virus, which the World Health Organization described on January 30, 2020 as a public health emergency of international concern, then returned to describe it as a pandemic on March 11, 2020, and the measures and procedures taken by government authorities in different countries of the world, whether at the highest level of imposing a comprehensive curfew or what is called globally home quarantine and thus disrupting all sectors and activities in the state, whether public or private (with the exception of some sectors such as the health, media and security sectors), or at a lower level than that, such as reducing work rates in different sectors by rates that vary from one country

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Publication Date
Tue Jun 14 2022
Journal Name
Al-academy
The prospects ability of contemporary epistemology for signification internal construction of plastic artwork
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Based on the systematic scientific investigation of artistic achievement, researchers (critics) adhere to mechanisms based on epistemology, through which it is envisaged to reveal the meaning of the achievement as the product of three actors: the effectiveness of an artistic sense, the effectiveness of an idea, and the arousal of taste according to systematic criticism procedures that investigate the new artistic achievement. Or, in a specific way, the possibility of meaning in all the accomplished from the aesthetics of artistic presentation and the character of the self-accomplished by the "artist" and the critic invokes his critical tools with certain cognitive foundations. In defining its nature from the rest of the other cultural ac

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Publication Date
Tue Feb 01 2022
Journal Name
Journal Of Physics: Conference Series
Study the effect of gamma Irradiation on the Superconducting Properties of HgBaSrCa2Cu3O8+δ
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Publication Date
Mon Dec 21 2020
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
A CONTRIBUTION TO THE CHECKLIST OF THE JUMPING SPIDERS (ARANEAE: SALTICIDAE) OF ARMENIA
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The paper presents an annotated checklist of the Salticidae of Armenia. This study was carried out in 2019-2020 in order to provide an inventory of the Salticidae fauna. Thirteen species are reported for the Armenian fauna for the first time: Afraflacilla epiblemoides (Chyzer, 1891); Aelurillus v-insignitus (Clerck, 1757); Asianellus festivus (C. L. Koch, 1834); Heliophanus dubius C. L. Koch, 1835; Heliophanus kochii Simon, 1868; Heliophanus tribulosus Simon, 1868; Heliophanus curvidens (O. Pickard-Cambridge, 1872); Macaroeris nidicolens (Walckenaer, 1802); Pellenes diagonalis (Simon, 1868); Pellenes geniculatus (Simon, 1868); Pellenes seriatus (Thorell, 1875); Pellenes tripunctatus (Walckenaer, 1802) and Phlegra fasciata (Hahn, 1826).

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