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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
Fri May 15 2009
Journal Name
Journal Of Planner And Development
ENHANCEMENT OF THE SOCIAL DIMENSION IN THE SUSTAINABLE ENVIRONMENT STRATEGY IN IRAQ
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Improving the environment is a mission that should be conducted by three associates; public authorities, environmentalists and the community. The ignorance of environmental education in Iraq has resulted to an almost environmentally illiterate community, demanding well planned programs to raise their environmental; awareness and education. On the other hand, the decision makers should be well informed about the citizens' environmental preferences to be able to set their priorities for the civil services. Merging the Iraqi citizens in listing their environmental priorities is one of many other approaches for "Environment Education" programs. Globally, such methods have proven to be effective and resulted to widespread understandin

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Publication Date
Wed Dec 01 2021
Journal Name
Baghdad Science Journal
Enhancement of Electron Temperature under Dense Homogenous Plasma by Pulsed Laser Beam
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The applications of hot plasma are many and numerous applications require high values of the temperature of the electrons within the plasma region. Improving electron temperature values is one of the important processes for using this specification in plasma for being adopted in several modern applications such as nuclear fusion, plating operations and in industrial applications. In this work, theoretical computations were performed to enhance electron temperature under dense homogeneous plasma. The effect of   power and duration time of pulsed Nd:YAG laser   was studied on the heating of   plasmas  by inverse bremsstrahlung  for  several values for the electron density ratio. There results for these ca

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Publication Date
Thu Jul 28 2016
Journal Name
Computer And Information Science
Refinement for Ocular Ultrasound Images Quality by Utilizing Combination of Enhancement Techniques
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Ultrasound has been used as a diagnostic modality for many intraocular diseases, due its safety, low cost, real time and wide availability. Unfortunately, ultrasound images suffer from speckle artifact that are tissue dependent. In this work, we will offer a method to reduce speckle noise and improve ultrasound image to raise the human diagnostic performance. This method combined undecimated wavelet transform with a wavelet coefficient mapping function: where UDWT used to eliminate the noise and a wavelet coefficient mapping function used to enhance the contrast of denoised images obtained from the first component. This methods can be used not only as a means for improving visual quality of medical images but also as a preprocessing

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Publication Date
Fri Dec 01 2023
Journal Name
Al-khwarizmi Engineering Journal
Working Memory Classification Enhancement of EEG Activity in Dementia: A Comparative Study
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The purpose of the current investigation is to distinguish between working memory ( ) in five patients with vascular dementia ( ), fifteen post-stroke patients with mild cognitive impairment ( ), and fifteen healthy control individuals ( ) based on background electroencephalography (EEG) activity. The elimination of EEG artifacts using wavelet (WT) pre-processing denoising is demonstrated in this study. In the current study, spectral entropy ( ), permutation entropy ( ), and approximation entropy ( ) were all explored. To improve the  classification using the k-nearest neighbors ( NN) classifier scheme, a comparative study of using fuzzy neighbourhood preserving analysis with -decomposition ( ) as a dimensionality reduction technique an

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Publication Date
Sat Dec 01 2018
Journal Name
Al-khwarizmi Engineering Journal
Enhancement of Hybrid Solar Air Conditioning System using a New Control Strategy
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Enhancement of the performance for hybrid solar air conditioning system was presented in this paper. The refrigerant temperature leaving the condenser was controlled using three-way valve, this valve was installed after the compressor to regulate refrigerant flow rate towards the solar system. A control system using data logger, sensors and computer was proposed to set the opening valve ratio. The function of control program using LabVIEW software is to obtain a minimum refrigerant temperature from the condenser outlet to enhance the overall COP of the unit by increasing the degree of subcooled refrigerant. A variable load electrical heater with coiled pipe was used instead of the solar collector and the storage tank to simulate the sola

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Publication Date
Fri Sep 01 2023
Journal Name
Journal Of Engineering
Dual Stages of Speech Enhancement Algorithm Based on Super Gaussian Speech Models
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Various speech enhancement Algorithms (SEA) have been developed in the last few decades. Each algorithm has its advantages and disadvantages because the speech signal is affected by environmental situations. Distortion of speech results in the loss of important features that make this signal challenging to understand. SEA aims to improve the intelligibility and quality of speech that different types of noise have degraded. In most applications, quality improvement is highly desirable as it can reduce listener fatigue, especially when the listener is exposed to high noise levels for extended periods (e.g., manufacturing). SEA reduces or suppresses the background noise to some degree, sometimes called noise suppression alg

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Publication Date
Sun Dec 27 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Phytochemical Investigation of the Aerial Part of Iraqi Convolvulus arvensis
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Convolvulus arvensis is a species of bindweed that is rhizomatous and is in the morning glory family (Convolvulaceae) native to Europe and Asia. The plant is naturally grown in Iraq. The plant was reported to be used in traditional medicine from as early as 1730s.

The Aerial parts of Convolvulus arvensis were macerated in 80% ethanol for 6 days. The concentrated extract was partitioned with n-hexane, chloroform, ethyl acetate- and n-butanol successively. The n-hexane and ethyl acetate, fractions were examined for the presence of phytochemicals by thin l

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Publication Date
Sat Jun 19 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Development, Characterization and Pharmacological Investigation of Umbelliferone Conjugates of NSAIDs
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The present investigation developed the ester prodrugs of Non-steroidal anti inflammatory drugs (NSAIDs), Mefenamic acid and Flurbiprofen by conjugating with the natural antioxidant, 4-methyl umbelliferone that resulted the formation of Mefenamic acid-umbelliferone ester prodrug and Flurbiprofen-umbelliferone ester prodrug .The principal objective this study is the synthesis of the ester prodrugs of NSAIDs with the enhanced therapeutic activity and minimized side effects. Prodrugs were synthesized by coupling method using N,N- dicyclohexylcarbodiimide/4-dimethylaminopyrimidine, subjected to  physical, chemical characterization, spectral characterization (IR, 1H NMR, 13C NMR and Mass spectra),hydro

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Publication Date
Thu Jun 01 2023
Journal Name
Journal Of Applied Sciences And Nanotechnology
Microstructure Investigation of Activated Carbon Prepared from Potato Peel
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Abstract This research investigates how activated carbon (AC) was synthesized from potato peel waste (PPW). Different ACs were synthesized under the atmosphere's conditions during carbonation via two activation methods: first, chemical activation, and second, carbon dioxide-physical activation. The influence of the drying period on the preparation of the precursor and the methods of activation were investigated. The specific surface area and pore volume of the activated carbon were estimated using the Brunauer–Emmett–Teller method. The AC produced using physical activation had a surface area as high as 1210 m2/g with a pore volume of 0.37 cm3/g, whereas the chemical activation had a surface area of 1210 m2/g with a pore volume of 0.34 c

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Publication Date
Mon Mar 27 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Phytochemical Investigation and Antioxidant Activity of Iraqi Tribulus terrestris
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The aim of the present study was to characterize the Iraqi Tribulus terrestris for the presence of biologically active phyto-chemicals using methanolic extracts of the plant (aerial parts) by Gas Chromatography –Mass spectrometry (GC/MS), while the mass spectra of the compounds found in the extract was matched with the National Institute of Standards and Technology (NIST) library , in addition to study the antioxidant activity of plant extract , results confirmed the presence of therapeutically potent compounds in the Iraqi Tribulus terrestris extract predominantly alkaloids, flavonoids, saponins, tannins and terpenoids. Antioxidant potential of Iraqi Tribulus terrestris

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