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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 Apr 23 2022
Journal Name
Research Journal Of Pharmacy And Technology
Synthesis, and Antimicrobial Evaluation of New hydrazone Derivatives of (2,4-dinitrophenyl) hydrazine
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In this work, novel compounds of hydrazones derived from (2,4-dinitrophenyl) hydrazine were synthesized. Benzamides derivatives and sulfonamides derivatives were prepared from p-amino benzaldehyde. Then these compounds were condensed with (2,4-dinitrophenyl) hydrazine through Imine bond formation to give hydrazones compounds. The compounds were characterized using FT-IR (IR Affinity-1) spectrometer, and 1HNMR analyses. The majority of the compounds have a moderate antimicrobial activity against “Gram-positive bacteria staphylococcus Aureus, and staphylococcus epidermidis, Gram-negative bacteria Escherichia coli, and Klebsiella pneumoniae, and fungi species Candida albicans” using concentrations of 250 µg\ml.

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Publication Date
Fri Jun 16 2023
Journal Name
Acta Scientiarum Polonorum Administratio Locorum
An analysis of Baghdad’s masterplans based on the development of green areas
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Motives: Baghdad is the capital city and an important political, administrative, social, cultural and economic centre of Iraq. Baghdad’s growth and development has been significantly influenced by efforts to accommodate various needs of its steadily growing population. Uncontrolled population and urban growth have exerted negative effects in numerous dimensions, including environmental sustainability because urban expansion occurred in green spaces within the city and the surrounding areas.Aim: The aim of this study was to examine the planning solutions in Baghdad’s green areas in the past and at present, and to identify the key changes in the city’s green areas, including changes in the ratio of green urban spaces to the tota

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Publication Date
Mon Apr 01 2019
Journal Name
Journal Of Engineering
The Influence of the Preparation and Stability of Nanofluids for Heat Transfer
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Recently the use of nanofluids represents very important materials. They are used in different branches like medicine, engineering, power, heat transfer, etc. The stability of nanofluids is an important factor to improve the performance of nanofluids with good results. In this research two types of nanoparticles, TiO2 (titanium oxide) and γ-Al2O3 (gamma aluminum oxide) were used with base fluid water. Two-step method were used to prepare the nanofluids. One concentration 0.003 vol. %, the nanoparticles were examined. Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM) and X-ray diffraction (XRD) were used to accomplish these tests. The stability of the two types of nanofluids is measured by

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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Factors Influence on the yield of Bacterial Cellulose of Kombucha (Khubdat Humza)
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Kombucha(Khubdat Humza) is composed of yeast and acetic acid bacteria especially, Acetobacter xylinum which forms a cellulose pellicle on tea broth. Kombucha(Khubdat Humza) produces bacterial cellulose pellicles, with unique purity and fine structure. It can be used in many forms, such as an emulsifier, stabilizer, dispersing agent, thickener and gelling agent but these are generally subsidiary to its most important use of holding on to water. Recently, bacterial cellulose is used in many special applications such as a scaffold for tissue engineering of cartilages and blood vessels, also for artificial skin for temporary covering of wounds, as well as its used in the clothing industry. The yield of cellulose produced were investiga

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Publication Date
Tue Oct 01 2019
Journal Name
October-2019
Histological assessment of the efficiency of rabbit serum in healing skin wounds
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Aim: This study aimed to investigate the impact of rabbit serum on skin wound healing with the help of histological examination. Materials and Methods: A total of ten indigenous rabbits were used in this study. The animals were divided into two groups: control and serum- treated. The histological assessment was done with a paraffin embedding technique and the histological sections were stained with H&E stain. Results: Severe infiltration of polymorphonuclear leukocytes with severe fibrin deposits were seen in serum treated group at 2 days post-injury; at 7 days post-injury the changes revealed moderate fibroplasia, fibrin deposit and severe infiltration of both mononuclear and polymorphonuclear leukocytes; at 14 days post-inju

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Publication Date
Mon Aug 01 2022
Journal Name
International Journal Of Electrical And Computer Engineering (ijece)
A survey of deepfakes in terms of deep learning and multimedia forensics
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Artificial intelligence techniques are reaching us in several forms, some of which are useful but can be exploited in a way that harms us. One of these forms is called deepfakes. Deepfakes is used to completely modify video (or image) content to display something that was not in it originally. The danger of deepfake technology impact on society through the loss of confidence in everything is published. Therefore, in this paper, we focus on deepfakedetection technology from the view of two concepts which are deep learning and forensic tools. The purpose of this survey is to give the reader a deeper overview of i) the environment of deepfake creation and detection, ii) how deep learning and forensic tools contributed to the detection

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Publication Date
Sat May 11 2024
Journal Name
Journal Of Optics
The effect of increasing temperature on the sensitivity of photonic crystal fiber
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Photonic Crystal Fiber Fabry–Perot Interferometers (FPI) based on Surface Plasmon Resonance (SPR) was investigated in this paper in order to detect changes in photonic crystal fiber sensitivity with increasing temperature. FPI is composed of a PCF (ESM-12) solid core spliced with a single-mode fiber (SMF) on one side and a 40nm thick gold Nano film on the other. In order to obtain the SPR curve, the end of PCF can be spliced with the side of SMF before covering the gold film on the PCF. SPR results are included in the suggested sensor, based on the conclusions of the investigations. Resolution (R) is 0.0871, Signal-to-Noise Ratio (SNR) is 0.1867, a figure of merit (FOM) is 0.0069, and sensitivity (S) is 1.1481 . This sensor proposed is s

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Publication Date
Wed Jun 07 2023
Journal Name
Journal Of Educational And Psychological Researches
A Proposed Training Program for School Leaders in the Sultanate of Oman on the Planning Practices of the Kaufman Model in Light of the Needs and Challenges of Reality
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The study aims to build a proposed training program for school leaders in the Sultanate of Oman on the planning practices of the Kaufman model in light of the needs and challenges of reality. It also aims to identify the challenges facing school leaders in practicing the stages of strategic planning. To achieve these objectives, the study adopted the descriptive approach due to its suitability to the nature of the study. A questionnaire was used to collect the needed data. The study sample included (225) individuals from school principals, their assistants and senior teachers in post-basic education in the Sultanate of Oman. After processing the data statistically, the study concluded that the reality of planning practices for school lea

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Publication Date
Sat Jul 01 2023
Journal Name
Journal Of Engineering
Using of Constructed Wetlands in The Treatment of Wastewater: A Review for Operation and Performance: Review for Using of Constructed Wetlands in The Treatment of Wastewater: Operation and Performance
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Wastewater recycling for non-potable uses has gained significant attention to mitigate the high pressure on freshwater resources. This requires using a sustainable technique to treat natural municipal wastewater as an alternative to conventional methods, especially in arid and semi-arid rural areas. One of the promising techniques applied to satisfy the objective of wastewater reuse is the constructed wetlands (CWs) which have been used extensively in most countries worldwide through the last decades. The present study introduces a significant review of the definition, classification, and components of CWs, identifying the mechanisms controlling the removal process within such units. Vertical, horizontal, and hybrid CWs

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Publication Date
Sun Dec 01 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Technical requirements for the application of economic intelligence and its impact On the dimensions of strategic success of banks: An applied research on a sample of Iraqi banks private
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This research sheds light on one of the important and vital topics for the banking sectors (technical requirements for the application of economic intelligence) namely by (Hardware, equipment, communication networks, software, databases). And the dimensions of the strategic success of the banks represented by(Customer satisfaction, customer trust, quality of service, growth) In the three Iraqi private banks, namely(Assyria International Investment, Mansour Investment, International Development Investment and Finance). Its implementation is an urgent necessity in order to improve the quality of its banking services to win the satisfaction of its customers and their confidence and then grow to achieve stra

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