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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
Thu Sep 01 2016
Journal Name
Journal Of Saudi Chemical Society
Synthesis and investigation of thermal properties of vanadyl complexes with azo-containing Schiff-base dyes
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Azo-Schiff base compounds (L1 and L2) have been synthesized from the reaction of m-hydroxy benzoic acid with 1,5-dimethyl-3-[2-(5-methyl-1H-indol-3-yl)-ethylimino]-2-phenyl-2,3- dihydro-1H-pyrazol-4-ylamine and with 3-[2-(1H-indol-3-yl)-ethylimino]-1,5-dimethyl-2-phenyl- 2,3-dihydro-1H-pyrazol-4-ylamine. The free ligands and their complexes were characterized based on elemental analysis, determination of metal, molar conductivity, (1H, 13C) NMR, UV–vis, FT-IR, mass spectra and thermal analysis (TGA). The molar conductance data revealed that all the complexes are non-electrolytes. The study of complex formation via molar ratio in DMF solution has been investigated and results were consistent to those found in the solid complexes with a rat

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Publication Date
Wed Dec 30 2015
Journal Name
College Of Islamic Sciences
Conflict investigation methodology Between the news and the work of the people of the city
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Praise be to Allah, Lord of the Worlds and prayers to our master and our beloved Muhammad and to his God and companions.
The Sunnah of the prophet completed the prayer and delivery agreed to accept them as evidence of legislation, and the fundamentalists differed in accepting the news of Sundays in the pieces, and most likely if the hadeeth is proven, and completed the correct conditions there is no objection to accept it in branches and pieces. As for the work of the people of the city is one of the evidence adopted when the imam Malik, who is the Imam of the House of the Prophet's blessed immigration, and scientists differ greatly. If you offer a ruling and the ruling of the Hadith of the individual, and the rule of the work of the

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Publication Date
Tue Mar 01 2022
Journal Name
Minar International Journal Of Applied Sciences And Technology
INVESTIGATION OF THE DENSITY OF STATE PROBABILITY FOR FE METAL CONTACT TO TIO2 SEMICONDUCTOR SYSTEM
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In this paper, the density of state (DOS) at Fe metal contact to Titanium dioxide semiconductor (TiO2) has been studied and investigated using quantum consideration approaches. The study and calculations of (DOS) depended on the orientation and driving energies. was a function of TiO2 and Fe materials' refractive index and dielectric constant. Attention has focused on the effect of on the characteristic of (DOS), which increased with the increasing of refractive index and dielectric constant of Fe metal and vice versa. The results of (DOS) and its relation with and values of system have been discussed. As for contact system is increased, (DOS) values increased at first, but the relation is disturbed later and transforms into an inve

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Publication Date
Wed Mar 30 2022
Journal Name
Iraqi Journal Of Science
Investigation of the Characteristics of CO (1-0) Line Integrated Emission Intensity in Extragalactic Spirals
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This paper aims to deal with the understanding of the properties of the molecular gas hydrogen in the extragalactic spirals sample. It is critical to make observations of CO (J = 1-0) line emission for spiral galaxies, particularly those with an energetic nucleus.  In the sample of spiral galaxies compiled, a carbon monoxide CO (1-0) emission line can be observed. This sample of galaxies' gas kinematics and star-forming should be analyzed statistically utilizing appropriate atomic gas HI, molecular gas H2, infrared (1μm-1000μm), visual (at λblue-optical=4400A0), and radio spectrum (at νradio=1.4 GHz and 5GHz) databases. STATISTICA is software that allows us to perform this statistical analysis. The presence of a high scale of s

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Publication Date
Tue Mar 01 2022
Journal Name
Journal Of Engineering
Numerical Investigation of the Flexure Behavior of Reinforced Concrete Spandrel Beams with Distributed Tension Reinforcement
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When the flange of a reinforced concrete spandrel beam is in tension, current design codes and specifications enable a portion of the bonded flexure tension reinforcement to be distributed over an effective flange width. The flexural behavior of the RC L-shaped spandrel beam when reinforcement is laterally displaced in the tension flange is investigated experimentally and numerically in this work. Numerical analysis utilizing the finite element method is performed on discretized flanged beam models validated using experimentally verified L-shaped beam specimens to achieve study objectives. A parametric study was carried out to evaluate the influence of various factors on the beam’s flexure behavior. Results showed that

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Publication Date
Mon Mar 23 2020
Journal Name
Journal Of Engineering
Experimental Investigation of Thermal Performance of a Solar Chimney Provided with a Porous Absorber Plate
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Experimental investigation of the influence of inserting the metal foam to the solar chimney to induce natural ventilation are described and analyzed in this work. To carry out the experimental test, two identical solar chimneys (without insertion of metal foam and with insertion of metal foam) are designed and placed facing south with dimensions of length× width× air gap (2 m× 1 m× 0.2 m). Four incline angles are tested (20o,30o,45o,60o) for each chimney in Baghdad climate condition (33.3o latitude, 44.4o longitude) on October, November, December 2018. The solar chimney performance is investigated by experimentally recording absorber pl

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Publication Date
Mon Jan 28 2013
Journal Name
Spie Proceedings
BER performance enhancement for secure wireless communication systems based on chaotic-MIMO techniques
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The growing interest in the use of chaotic techniques for enabling secure communication in recent years has been motivated by the emergence of a number of wireless services which require the service provider to provide low bit error rates (BER) along with information security. This paper investigates the feasibility of using chaotic communications over Multiple-Input-Multiple-Output (MIMO) channels. While the use of Chaotic maps can enhance security, it is seen that the overall BER performance gets degraded when compared to conventional communication schemes. In order to overcome this limitation, we have proposed the use of a combination of Chaotic modulation and Alamouti Space Time Block Code. The performance of Chaos Shift Keying (CSK) wi

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Publication Date
Tue Aug 22 2017
Journal Name
Heat Transfer—asian Research
Thermal Enhancement from Pin Fins by Using Elliptical Perforations with Different Inclination Angles
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Abstract<p>Many of the proposed methods introduce the perforated fin with the straight direction to improve the thermal performance of the heat sink. The innovative form of the perforated fin (with inclination angles) was considered. Present rectangular pin fins consist of elliptical perforations with two models and two cases. The signum function is used for modeling the opposite and the mutable approach of the heat transfer area. To find the general solution, the degenerate hypergeometric equation was used as a new derivative method and then solved by Kummer's series. Two validation methods (previous work and Ansys 16.0‐Steady State Thermal) are considered. The strong agreement of the validation results (0.3</p> ... Show More
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Publication Date
Mon Nov 22 2021
Journal Name
Nanomaterials
Melting Enhancement in a Triple-Tube Latent Heat Storage System with Sloped Fins
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Due to the potential cost saving and minimal temperature stratification, the energy storage based on phase-change materials (PCMs) can be a reliable approach for decoupling energy demand from immediate supply availability. However, due to their high heat resistance, these materials necessitate the introduction of enhancing additives, such as expanded surfaces and fins, to enable their deployment in more widespread thermal and energy storage applications. This study reports on how circular fins with staggered distribution and variable orientations can be employed for addressing the low thermal response rates in a PCM (Paraffin RT-35) triple-tube heat exchanger consisting of two heat-transfer fluids flow in opposites directions throug

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Publication Date
Sat Nov 01 2025
Journal Name
Journal Of Molecular Liquids
Chitosan salt as a dual-function agent for CO₂ sequestration and acidizing enhancement
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The utilization of carbon dioxide (CO₂) to enhance wellbore injectivity presents a cost-effective and sustainable strategy for mitigating greenhouse gas emissions while improving reservoir performance. This study introduces an environmentally friendly method employing a water-soluble chitosan salt (CS) that generates a carbonated-rich acid solution upon contact with dry CO₂ at 25 °C and 508 psi. CS solutions (100–2000 ppm) were prepared and evaluated for CO₂ uptake, acid generation, and rheological behavior. Results show that 1000 ppm achieves an optimal CO2 uptake (2612 mg/l), with moderate viscosity increase (from 1.52 to 3.37 cp), while higher concentrations exhibit a sharp rise due to polymer-like network formation. Core floodi

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