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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 Dec 06 2018
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Enhancement of the Solubility and Dissolution Rate of Rebamipide by Using Solid Dispersion Technique (Part I)
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Solid dispersion is an attractive tool of pharmaceutical technology used to improve the physical properties of drugs. Among these properties is to enhance the solubility of the drugs.
Rebamipide is a poorly soluble drug of class IV of biopharmaceutical classification system (BCS).
Rebamipide is used as potent antiulcer, mucoprotective drug, by stimulating the generation of prostoglandine enhanced mucosal protection.
Rebamipide was formulated as a solid dispersion using different polymers such as pluronic F-127, PEG6000, PVP K30, and TPGS by using different preparation methods solvent evaporation, fusion, and kneading methods.
It was seen that rebamipide was successfully dispersed in a homogenous solid dispersion matrix by sol

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Publication Date
Wed May 10 2023
Journal Name
Journal Of Engineering
An Investigation into Heat Transfer Enhancement by Using Oscillating Fins
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The present work describes numerical and experimental investigation of the heat transfer characteristics in a plate-fin, having built-in piezoelectric actuator mounted on the base plate (substrate). The geometrical configuration considered in the present work is representative of a single element of the plate-fin and triple fins. Air is taken as the working fluid. A performance data for a single rectangular fin and triple fins are provided for different frequency levels (5, 30 and
50HZ) , different input power (5,10,20,30,40 and 50W) and different inlet velocity (0.5, 1, 2, 3, 4, 5 and 6m/s) for the single rectangular fin and triple fins with and without oscillation. The investigation was also performed with different geometrical fin

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Publication Date
Fri May 31 2019
Journal Name
Journal Of Engineering
Numerical Investigation of Heat Transfer Enhancement of Double Pipe Heat Exchanger Using Metal Foam Fins
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The influence of adding metal foam fins on the heat transfer characteristics of an air to water double pipe heat exchanger is numerically investigated. The hot fluid is water which flows in the inner cylinder whereas the cold fluid is air which circulates in the annular gap in parallel flow with water. Ten fins of metal foam (Porosity = 0.93), are added in the gap between the two cylinder, and distributed periodically with the axial distance. Finite volume method is used to solve the governing equations in porous and non-porous regions. The numerical investigations cover three values for Reynolds number (1000 ,1500, 2000), and Darcy number (1 x10-1, 1 x10-2, 1x10-3). The comparison betwee

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Publication Date
Sun May 01 2016
Journal Name
Journal Of Engineering
Experimental Investigation of Convection Heat Transfer Enhancement in Horizontal Channel Provided with Metal Foam Blocks
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Convection heat transfer in a horizontal channel provided with metal foam blocks of two numbers of pores per unit of length (10 and 40 PPI) and partially heated at a constant heat flux is experimentally investigated with air as the working fluid. A series of experiments have been carried out under steady state condition. The experimental investigations cover the Reynolds number range from 638 to 2168, heat fluxes varied from 453 to 4462 W/m2, and Darcy number 1.77x10-5, 3.95x10-6. The measured data were collected and analyzed. Results show that the wall temperatures at each heated section are affected by the imposed heat flux variation, Darcy number, and Reynolds number variation. The var

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Publication Date
Tue May 16 2023
Journal Name
Journal Of Engineering
Experimental Investigation Utilizing Thermal Image Technique to the Heat Transfer Enhancement Using Oscillated Fins
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Heat transfer around a flat plate fin integrated with piezoelectric actuator used as oscillated fin in laminar flow has been studied experimentally utilizing thermal image camera. This study is performed
for fixed and oscillated single and triple fins. Different substrate-fin models have been tested, using fins of (35mm and 50mm) height, two sets of triple fins of (3mm and 6mm) spacing and three frequencies
applied to piezoelectric actuator (5, 30 and 50HZ). All tests are carried out for (0.5 m/s and 3m/s) in subsonic open type wind tunnel to evaluate temperature distribution, local and average Nusselt number (Nu) along the fin. It is observed, that the heat transfer enhancement with oscillation is significant compared to without o

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Publication Date
Fri Sep 29 2017
Journal Name
Journal Of Engineering
Studying the Improvement of the Solubility of Cellulosic Fibers
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This study focuses for improving the increase the solubility of fiber cellulose in sodium hydroxide solution in concentrations ranging from (4- 12%), from one point of view and from other point of view in (sodium hydroxide and urea) solution concentration (6% NaOH + 4% urea), under  low temperature (- 15, - 20 Co) , depending on the principle of  reducing the degree of polymerization for  fiber cellulose, which is represented in our tests cotton linter who its represent  (Whatman filter paper, Grade 1), some samples subjected to chemical pretreatment as simulation the method of decomposition of cellulosic materials by white or brown fungi that grow on trees, this method involves the use of

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Publication Date
Mon Nov 29 2021
Journal Name
Iraqi Journal Of Science
Comparing the Main Approaches of Image Segmentation
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Images are important medium for conveying information; this makes improvement of image processing techniques also important. Interpretation of image content is one of the objectives of image processing techniques. Image interpretation that segments the image to number of objects called image segmentation. Image segmentation is an important field to deal with the contents of images and get non overlapping regions coherent in texture and color, it is important to deal only with objects with significant information. This paper presents survey of the most commonly used approaches of image segmentation and the results of those approaches have been compared and according to the measurement of quality presented in this paper the Otsu's threshol

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Publication Date
Mon May 01 2023
Journal Name
Journal Of Engineering
Experimental Investigation of Heat Transfer Enhancement in a Double Pipe Heat Exchanger Using Compound Technique of Transverse Vibration and Inclination Angle
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Numerous tests are recently conducted to assess vibration's role in accelerating the heat transfer rate in various heat exchangers. In this work, the enhancement of heat transfer by the effect of transfer vibration and inclination angles on the surface of a double pipe heat exchanger experimentally has been investigated. A data acquisition system is applied to record the data of temperatures, flow rates, and frequencies over the tests. A compound technique was adopted, including the application of a set of inclination angles of (0°, 10°, 20°, and 30°) under the effect of frequency of vibration ranging from sub-resonance to over-resonance frequencies. The results showed that the overall heat transfer coefficient enhan

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Publication Date
Sat Oct 09 2021
Journal Name
Nanomaterials
Investigation of Heat Transfer Enhancement in a Triple Tube Latent Heat Storage System Using Circular Fins with Inline and Staggered Arrangements
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Inherent fluctuations in the availability of energy from renewables, particularly solar, remain a substantial impediment to their widespread deployment worldwide. Employing phase-change materials (PCMs) as media, saving energy for later consumption, offers a promising solution for overcoming the problem. However, the heat conductivities of most PCMs are limited, which severely limits the energy storage potential of these materials. This study suggests employing circular fins with staggered distribution to achieve improved thermal response rates of PCM in a vertical triple-tube heat exchanger involving two opposite flow streams of the heat-transfer fluid (HTF). Since heat diffusion is not the same at various portions of the PCM unit,

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Publication Date
Thu Jun 09 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Improvement of the Solubility and Dissolution Characteristics of Risperidone via Nanosuspension Formulations
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Risperidone is an atypical antipsychotic drug that is used for treating schizophrenia, bipolar mania, and autism. Risperidone rebalances dopamine and serotonin to improve thinking, mood, and behavior by working on dopamine and serotonin α2receptor antagonism. Risperidone has poor solubility and high permeability through the intestine, so it belongs to Biopharmaceutical Classification System (BCS) class II exhibits poor oral biopharmaceutical properties.

 The aim of the present work was to improve solubility and dissolution of Risperidone by preparing nanosuspension using different stabilizers and different solvents‎ in a method known as solvent-antisolvent precipitation method.  Twenty-eight formulas were prepared

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