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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
Wed Dec 27 2023
Journal Name
Journal Of Planner And Development
The impact of infrastructure planning of complete street elements on the urban environment
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In contemporary cities, the expansion of the use of vehicles has led to the deterioration of the urban environment. To counter this, many concepts and strategies emerged that attempted to regulate mobility in cities and limit its effects. The concept of a "complete street" is one of the modern trends concerned with diversifying means of transportation and reducing the disadvantages of mechanical transportation methods This paper discusses the role that complete streets can play in developing the urban environment in the Alyarmok District of Baghdad, which suffers from traffic congestion and its associated problems.In this study, 104 people were surveyed in the Alyarmok region, and the linear regression method was used to analyze their op

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Publication Date
Tue May 16 2023
Journal Name
Journal Of Engineering
Application of Wavelet Packet and S Transforms for Differential Protection of Power Transformer
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The differential protection of power transformers appears to be more difficult than any type of protection for any other part or element in a power system. Such difficulties arise from the existence of the magnetizing inrush phenomenon. Therefore, it is necessary to recognize between inrush current and the current arise from internal faults. In this paper, two approaches based on wavelet packet transform (WPT) and S-transform (ST) are applied to recognize different types of currents following in the transformer. In WPT approach, the selection of optimal mother wavelet and the optimal number of resolution is carried out using minimum description length (MDL) criteria before taking the decision for the extraction features from the WPT tree

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Publication Date
Sat Jan 25 2020
Journal Name
International Journal Of Research In Pharmaceutical Sciences
Determination of the Dissociation Constants of Metformin from a Second Derivative UV Spectrum
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An environmentally begnin second derivative spectrometric approach was developed for the estimation of the dissociation constants pKa(s) of metformin, a common anti-diabetic drug.  The ultraviolet spectra of the aqueous solution of metformin were measured at different acidities, then the second derivative of each spectrum was graphed. The overlaid second derivative graphs exhibited two isobestic points at 225.5 nm and 244 nm pointing out to the presence of two dissociation constants for metformin pKa1 and pKa2, respectively. The method was validated by evaluating the reproducibility of the acquired results by comparing the estimated values of the dissociation constants of two different strategies that show excellent matching. As we

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Publication Date
Sun Jun 04 2017
Journal Name
Baghdad Science Journal
Texture Analysis of smear of Leukemia Blood Cells after Exposing to Cold Plasma
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Plasma physics and digital image processing technique (DIPT) were utilized in this research to show the effect of the cold plasma (plasma needle) on blood cells. The second order statistical features were used to study this effect. Different samples were used to reach the aim of this paper; the patients have leukemia and their leukocytes number was abnormal. By studying the results of statistical features (mean, variance, energy and entropy), it is concluded that the blood cells of the sample showed a good response to the cold plasma.

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Publication Date
Wed Apr 11 2007
Journal Name
Journal Of Al-nahrain University
KINETICS AND MECHANISM STUDIES OF OXIDATION OF Α-AMINO ACIDS BY N-BROMOSUCCINIMIDE
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Kinetics and mechanism studies of oxidation of some α-amino acids (Proline, Arginine, Alanine) (AA) by N-Bromosuccinimide (NBS) by using conductivity method was carried out. The kinetic study showed that the reaction was first order with respect to NBS and AA. The effect of addition of HClO4 to the reaction was negative on the rate of reaction. The reaction was carried out at different temperatures in which  * * *   , S , G were calculated. The rate of reaction of AA was as follows: Proline > Arginine > Alanine

Publication Date
Mon Nov 01 2021
Journal Name
Archives Of Razi Institute
Effect of Leishmania major infection on the expression of TGF beta in murine
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Leishmania major is a protozoan parasite that causes cutaneous Leishmaniasis disease in human beings and animals. The disease is prevalent in tropical and semitropical countries and has great health importance. The present study aimed to identify the histological changes in the organs infected with L. major and to provide a sophisticated diagnostic method for infection through detecting TGF-β cytokine by immunohistochemistry technique(IHC) from October 2020 to January 2021. A total of 40 samples of paraffin blocks were used for different organs including skin, spleen, liver, kidney, and heart of male and female BALB/c mice, aged 6-8 weeks, which were previously infected subcutaneously with L. major promastigotes at a dose of 1×107 promast

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Publication Date
Sat Jan 01 2022
Journal Name
المجلة العراقية لعلوم التربة
EFFECT OF UREA AND NPK FERTILIZER ON SOME PHYSIOLOGICAL CHARACTERISTICS OF WATERCRESS PLANT
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The experiment was conducted in the botanical garden of the Department of Life Sciences/ College of Education for Pure Sciences Ibn Al-Haitham for the growing season 2021- 2020 in order to study the effect of urea and NPK fertilizer on some physiological characteristics of watercress plants. The seeds were sown on 10/15/2020 in plastic bags weighing 10 kg of soil. The shoots were sprayed with urea at three concentrations (0, 50, 100) mg L-1 in two sprays, and NPK fertilizer was added as a ground addition at three levels (0, 100, 200) kg H-1 in two sprays in conjunction with urea spraying. The results of the study showed a significant effect for the single treatments. The treatment of spraying with urea at a concentration of 50 mg l-1 . was

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Publication Date
Mon Feb 01 2016
Journal Name
American Journal Of Dentistry
Effect of adhesive materials on shear bond strength of a mineral trioxide aggregate
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Publication Date
Sun Oct 27 2019
Journal Name
Journal Of Global Pharma Technology
Adsorption Thermodynamic Study of Congo Red Dye on Electrospun Nanofibers Mat of Polyacrylonitrile
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The present study intends to prepare nanofibers mat of polyacrylonitrile by electrospinning technique and investigates their adsorption capacity to Congo red dye from the aqueous solution, after characterize it by different techniques such as FTIR, SEM, EDA, XRD and BET. The influence factors on adsorption were studied including adsorbent dosage, initial concentration, contact time, pH and ionic strength. The results confirmed that the increasing in pH decreases the adsorption capacity. So, the optimum adsorbent dosage, initial concentration and contact time were 0.006 g, 25 mg/L and 150 min respectively. The isotherm models of Freundlich and Langmuir were applied on the experimental adsorption data to evaluate the maximum capacity and ener

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Publication Date
Sun Sep 01 2013
Journal Name
Baghdad Science Journal
Synthesis and Evaluation of Antimicrobial activity of several new Maleimides to Benzothiazole moiety
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In this work, a series of new maleimides linked to substituted benzothiazole moiety were synthesized. Synthesis of these new cyclic imides were performed via three steps, the first one involved preparation of a series of 2-aminobenzothiazole substituted with different substituents via reaction of different primary aromatic amines with ammonium thiocyanate and bromine in glacial acetic acid. The prepared 2- amino benzothiozoles were introduced in the second step in reaction with maleic anhydride producing a series of N-(substituted benzothiazole-2-yl) maleamic acids.The resulted maleamic acids were dehydrated in the third step via treatment with acetic anhydride and anhydrous sodium acetate to afford a series of the desirable N-(substitu

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