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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
Sun Nov 01 2015
Journal Name
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Topical 40% Loranthus europaeus Ointment Versus Topical 25% Podophyllin Solution in the Treatment of Acute Cutaneous Leishmaniasis (Single Blinded, Therapeutic, Comparative study)
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Tue Jan 01 2019
Journal Name
International Journal Of Pharmaceutical Research
New method for the evaluation of propranolol with phosphotungstic acidvialong distance chasing photometer (NAG-ADF-300-2) using continuous flow injection analysis
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A new, simple and sensitive method was used forevaluation of propranolol withphosphotungstic acidto prove the efficiency, reliability and repeatability of the long distance chasing photometer (NAG-ADF-300-2) using continuous flow injection analysis. The method is based on reaction between propranolol and phosphotungstic acid in an aqueous medium to obtain a yellow precipitate. Optimum parameters was studied to increase the sensitivity for developed method. A linear range for calibration graph was 0.007-13 mmol/L for cell A and 5-15 mmol/L for cell B, and LOD 207.4792 ng/160 µL and 1.2449 µg/160 µL respectively to cell A and cell B with correlation coefficient (r) 0.9988 for cell A, 0.9996 for cell B, RSD% was lower than 1%, (n=8) for the

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Tue Jan 01 2019
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Energy Procedia
The relationship of Nuclear Decay Methods (alpha and beta) Particles with the Nuclear Deformation for Nuclei inUranium-238 and Thorium -232 Series
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Sun Dec 01 2019
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Central Bank control of external transfers and its impact on the tax information system: Applied research in the General Authority for Taxes
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Tax information system is one of the most important means that help the tax administration to reach the real income of the taxpayer, and the problem of research came in the General Authority for Tax ,The next question (Does the control carried out by the Central Bank on foreign remittances to reach the real income of the taxpayer). The research is gaining importance by focusing on the Central Bank's control over foreign remittances, and how to use this control to finance the tax information system. The relationship between the Central Bank's control over foreign remittances and the tax information system.The study has reached a number of recommendations, the most important of which are the following: The work of an integrated information

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Publication Date
Sun Mar 18 2018
Journal Name
Https://www.iasj.net/iasj/article/170012#:~:text=al.qadisiya%20journal%20for%20the%20sciences%20of%20physical%20education
The Effect Of Using Two Strategies For Active Learning ( Jigsaw Strategy & Problems Solving) In Learning Some Balanced Beam's Skills In Artistic Gymnastics
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The aim of this study to identify the effect of using two strategies for active learning ( Jigsaw Strategy & Problems Solving) in learning some balanced beam's skills in artistic gymnastics for women , as well as to identify the best of the three methods (jigsaw strategy , problems solving and the traditional method) in learning some skills balance beam , the research has used the experimental methodology, and the subject included the students of the college of Physical Education and Sports Sciences / University of Baghdad / third grade and by the lot was selected (10) students for each group of groups Search three and The statistical package for social sciences (SPSS) was used means, the standard deviation and the (T.test), the one way a n

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Publication Date
Sun Mar 01 2020
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Asset Utilization Efficiency and its effect on the sustainable Stockholder’s Wealth: Apply Study of Iraqi Companies listed on the Iraqi Stock Exchange
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Publication Date
Mon Jan 01 2018
Journal Name
World Journal Of Dentistry
Obturation of Lateral Canals by a New Reciprocating Spreader and a Conventional Finger Spreader by Lateral Condensation Technique: in vitro Comparative Study
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Plasma parameters of Au nano-particles ablated on porous silicon produced via Nd-YAG laser at 355 nm for sensing NH3 gas
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a laser ablation Q-switched Nd: YAG laser with a wave-length of 355 nm at a variety of laser pulse energies (E) and deposited on porous silicon (PS). Optical emission spectrometer was used to diagnosed medium air to study gold plasma characteristics and prepared Au nanoparticles. The laser pulse energy influence has been studied on the plasma characteristics in air. The data showed the emergence of the ionic (Au II) spectral emission lines in the gold plasma emission spectrum. XRD has been utilized to examine structural characteristics. Moreover, AFM results 37.2 nm as the mean value of the diameter that is coordinated in a shape similar to the rod that appears for Au NPs, in addition to that, TEM has been an indication of the fact that syn

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Publication Date
Mon Jun 01 2009
Journal Name
Journal Of Economics And Administrative Sciences
Simulation of material requirements planning system According to FOQ, EOQ, L4L A study in the General Company for woolen industries / blankets factory
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This paper is submitted as anew approach to simulate manufacturing control & planning system to define the problem of designing control system on the needs for materials.

Production planning & control is a total and complex operation, resides in the essence of manufacturing companies operations. The successful process of production planning and control systems is critical for the staying of manufacturing organizations in markets leading to the increasing consumer competition and which dominate most of manufacturing sectors because of the market oriented economy , thus , what has happened previously , that the companies possessed a great inventory of crude material, components, and groupings and they use in flexible techni

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Publication Date
Fri Jul 01 2016
Journal Name
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The role of the Organizational Service Orientation practices and its Impact in inhancing the employees performance (A Fiald Research in Baghdad Municipality)
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Abstract:

Recently, there is a widespread attention about the service at the level of each of the research and academic studies, and at the organizational level as well. The subject of orientation towards the service aspect is starting to be of this attention being of the modern subjects, relatively, which appeared at the end of the last century, as well as the link of this subject with the relationship between the organization and its customers, and how to provide high quality services to get their satisfaction. Thus, the specialists from researchers were interested in this field to develop an appropriate scale to measure the organizational orientation toward service, and it was the most prominen

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