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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 Mar 10 2021
Journal Name
Baghdad Science Journal
Theoretical Investigations of Vibrational – Rotational Energy of some Hydrogen Halide Molecules
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A theoretical study by using computer model is presented to study the energy characteristics of the vibrational – rotational levels as a function of the vibrational and rotational quantum number, respectively. The calculations were based on the basis of a multilevel model taking into account the non-equilibrium population of the rotational levels. The computational investigation has been performed to examine the vibrational-rotational characteristics of some hydrogen halides chemical laser molecules. This program takes into account the various molecules of chemical lasers such as, Hydrogen Fluoride (HF), Deuterium Fluoride (DF), Hydrogen Chloride (HCl), and Deuterium Chloride (DCl). The practical difficulties associated with this

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Publication Date
Sun Dec 30 2018
Journal Name
Baghdad Science Journal
Synthesis and study of biological activity of some new Imidazole derivatives
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In this work ester derivatives were synthesized by the reaction of imidazole derivatives (C1) with ethylchloroacetate in ethanol and NaOH to give the corresponding (C2) .While compound (C3) acetohydrazide was synthesized by the reaction of ester derivatives (C2) with hydrazine hydrat in ethanol. Compound (C3) from the reaction with different aromatic aldehydes in absolute ethanol gave the Schiff′s bases (C4,C5). The product compounds were characterized by FT-IR, U.V and 1HNMR spectra and the biological activities were studied as antibacterial.

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Publication Date
Fri Mar 31 2017
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Effect of Nanoparticles and Surfactant on Phase Inversion of Two Phases
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In the present study, a pressure drop technique was used to identify the phase inversion point of oil-in-water to water-in-oil flows through a horizontal pipe and to study the effect of additives (nanoparticles, cationic surfactant and blend  nanoparticles-surfactant) on the critical dispersed volume fraction (phase inversion point). The measurements were carried  for mixture velocity ranges from 0.8 m/sec to 2.3 m/sec. The results showed that at low mixture velocity 0.8 and 1 m/sec there is no effect of additives and velocity on phase inversion point, while at high mixture velocities the phase inversion point for nanoparticles and blend (nanoparticles/surfactant) systems was delayed (postponed) to a higher value of the dispers

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Publication Date
Sun Dec 02 2018
Journal Name
Journal Of The College Of Education For Women
The Level of Career Involvement of Primary School Managers in Baghdad
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The study aimed to identify career engagement among school principals, the researcher used descriptive approach and reached the study sample (230) school, principals. The researcher instruments used: career engagement, has been checked and face validity, and construction and consistency of the instruments using internal consistency Cronbach's alpha The study came to the following findings: - The degree of career engagement among school principals was (29.0200) this refers to a higher level, compared with the theoretical average of (27) and the study showed that the results showed no significant statistical differences between school principals in the level of career engagement due to the variable sex.

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
synthesis and studies of mixed-Ligand complexes of some transition Elements
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I've been in this work to prepare some complexes containing mixed Kandat with some transitional elements which new complexes according to the best of our knowledge and to refer to the information from the Internet until I have been studying this diagnosis Aalmakdat

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Publication Date
Sun Mar 06 2016
Journal Name
Baghdad Science Journal
Prevalence of Urinary Schistosomiasis in Al-Rusafah Regions of Baghdad governarate
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Urinary Schistosomiasis is one of important diseases that cause irritation and damage of urinary tract and other systems and tissues and can not be expected by doctors when diagnosing urinary tract diseases.The current study is conducted to investigate the prevalence of schistosomiasisin Baghdad / Al-Rusafa. 191urine samples were collected fromresidents ofsome areas of Al-Rusafain Baghdad governarate (Almashtal, Albaladyat, Alameen, Baghdad aljadida and Alnahrawan) for the period from March until the end of September 2010.The samples were examined by the precipitation and examination of micro hematuria by reagent strips. The total infection percentage was 9.42% (18/191) and was significantly higher in males compared tofemales12.64% (11/87)

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Publication Date
Wed Mar 29 2023
Journal Name
Journal Of The College Of Education For Women
Geographical Analysis of Sanitation Workers in the Urban District of Kut
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Cleaning is one of the services provided by the state and its ad hoc institutions. Every developed country is clean due to the good planning and attention given to the staff of all municipalities and service institutions. Beside, the attention paid to this sector is considered one of the windows to maintain the states’ aesthetics. If janirtos stop disposing of all the discarded wastes, the result will be having big piles of waste, affecting accordingly the health and safety of its citizens and the aesthetics of the areas. The janitors and those responsible for them are tha staff that the state must take care of because of their importance to the state in general and to the province in particular. The importance of the research

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Publication Date
Wed Jan 01 2020
Journal Name
2nd International Conference On Materials Engineering & Science (iconmeas 2019)
New application of pervaporation to enhance the conversion of consecutive reaction
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This study investigates consecutive reaction assisted by pervaporation for the first time. It studies the saponification of diethyladipate DA with sodium hydroxide NaOH solution synchronous with separating ethanol from the reaction mixture through an aqueous – organic membrane. The effect of time on some variables such as: permeated ethanol concentration EtOH wt%, separation factor (α), concentration of NaOH solution CB in the reaction medium and the conversion of DA to monoethyladipate (the intermediate product) was studied. It was shown that EtOH wt% and the conversion increased with increasing time unlike CB but (α) showed the existence of maximum value during the time of experiment. The process of reaction assisted by pervaporation

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Publication Date
Wed Aug 21 2019
Journal Name
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Evaluation of the Performance of Glasphalt Concrete Mixtures for Binder Course
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Publication Date
Mon Jan 01 2018
Journal Name
Ournal Of Advanced Research In Dynamical And Control System
Effect of magnetic field on peristaltic transport of bingham plastic fluid
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