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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
Tue May 01 2018
Journal Name
Journal Of Physics: Conference Series
Multispectral and Panchromatic used Enhancement Resolution and Study Effective Enhancement on Supervised and Unsupervised Classification Land – Cover
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Publication Date
Mon May 22 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Role of Omeprazole in Enhancement of Antibiotic Resistance in E. coli
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E. coli was isolated, and it was Gram-negative rod bacteria that was colony circular, regular edged, thick somewhat glitter and  viscous(less). It was lactose fermenter bacteria and belongs the family of Enterobacteriaceae. E. coli showed sensitivity to all used antibiotics except Erythromycin (E), Cloxacellin (CX), Rifampin (RA), Cephalothin (KF), Ampicillin (AM), and Penicillin (P). The experimental results of antibiotic sensitivity of E. coli in media containing different concentrations of omeprazole, a proton pump inhibitor, showed an enhancement of resistance by decreasing the sensitivity of E. coli inversely with drug concentration against the antibiotics that E. coli was sensitive to. It seems that omeprazole changed cell mem

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Tue Mar 31 2020
Journal Name
International Journal Of Heat And Technology
Enhancement of Natural Convection Heat Transfer of Hybrid Design Heat Sink
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Tue May 23 2023
Journal Name
Journal Of Engineering
Enhancement of the Detection of the TCP SYN Flooding (DDoS) Attack
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Publication Date
Wed Feb 15 2023
Journal Name
Remote Sensing
Combining Remote Sensing Approaches for Detecting Marks of Archaeological and Demolished Constructions in Cahokia’s Grand Plaza, Southwestern Illinois
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Remote sensing data are increasingly being used in digital archaeology for the potential non-invasive detection of archaeological remains. The purpose of this research is to evaluate the capability of standalone (LiDAR and aerial photogrammetry) and integration/fusion remote sensing approaches in improving the prospecting and interpretation of archaeological remains in Cahokia’s Grand Plaza. Cahokia Mounds is an ancient area; it was the largest settlement of the Mississippian culture located in southwestern Illinois, USA. There are a limited number of studies combining LiDAR and aerial photogrammetry to extract archaeological features. This article, therefore, combines LiDAR with photogrammetric data to create new datasets and inv

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Publication Date
Wed Dec 09 2015
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
Effect of Sodium sulfite treatment on the trypsin inhibitors activity, protein isolate and protein solubility of complete and dehulling white bean seeds Phaseolus vulgaris.: Effect of Sodium sulfite treatment on the trypsin inhibitors activity, protein isolate and protein solubility of complete and dehulling white bean seeds Phaseolus vulgaris.
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The study aimed to increase the biological value of white bean. The effect of different concentrations 0.01 ,0.02,0.03,and 0.04 M of sodium sulfite solutions for 1hr at 70 ºC on the trypsin inhibitors activity, protein isolate and protein solubility of complete and dehulling white bean flour were studied.Trypsin inhibitors activity were reduced by 42.97, 58.69, 68.59 and 69.58% in complete white bean flour at 0.01 ,0.02, 0.03, 0.04 M respectively, while the corresponding values were 50.43, 61.00, 75.61 and 85.66% respectively in dehulling white bean flour .Protein isolate value was 13.41% and protein solubility was 2.2% in control sample, Furthermore, the using of chemical treatment showed that protein isolate was reduced gradually and

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Publication Date
Mon Mar 27 2017
Journal Name
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Photocurrent enhancement of heat treated CdSe-sensitized titania nanotube photoelectrode
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Publication Date
Thu May 11 2017
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Enhancement of Stream Cipher by Using Variant Register in Length
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         Stream ciphers are an important class of encryption algorithms. There is a vast body of theoretical knowledge on stream ciphers, and various design principles for stream ciphers have been proposed and extensively analyzed. This paper  presents a new method of stream cipher, that by segmenting the plaintext into number of register then any of them combined to any other by using combination logic circuit (And, OR, JK, NOT, XOR), then using variant register in length as a key which provides security enhancement against attacks and then compare the strength of this method with RSA by calculaing the time necessary to get the original text by using the genetic algorithm. And the way that ha

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Publication Date
Sat Mar 19 2022
Journal Name
Al-khwarizmi Engineering Journal
Enhancement of System Security by Using LSB and RSA Algorithms
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Publication Date
Fri Nov 29 2019
Journal Name
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Enhancement In Ballistic Performance Of Composite Armor Through Nano Ceramic
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