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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 Jan 05 2024
Journal Name
Al-academy
Designs treatment of the internal spaces of pharmacies
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The pharmacy is the face for the health buildings and hospitals, The linking professional relationships and functional, it is been from the important places that most people go it, so according to that we must format its interior design in form that suitable with the need of most people use it or work in it, and this the search goal, dashing from the search subject which to hide finding designer treatment for the pharmacies interior spaces, to give share in the functional improvement performance or aesthetic. We define the search goals to share in educate the pharmacist in the effect of interior design for improvement of interior environment, in addition to the search consider as designer trying add to the other trying the interior desig

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Publication Date
Fri Dec 30 2011
Journal Name
Al-kindy College Medical Journal
Outcome of surgical treatment of highgrade intramedullary astrocytomas
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Background: Intramedullary astrocytomas
account for about 1% of all CNS tumors and
6–8% of spinal cord tumors. The vast majority
of intramedullary astrocytomas are slowgrowing
lesions.
Objectives: The goal in this study was to
review a series of patients who underwent
surgical removal of intramedullary high-grade
astrocytomas, focusing on the functional
outcome and the effect of multimodality
treatment on the survival of patients with high
grade intramedullary astrocytoma.
Methods: Between June 1999 and June 2004,
22 patients underwent removal of
intramedullary high-grade astrocytomas in four
neurosurgical hospital in Baghdad/ Iraq
(Neurosurgical hospital, Al Shaheed Adnan
Hospital for

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Publication Date
Sat Feb 02 2019
Journal Name
Journal Of The College Of Education For Women
THE EFFECT OF SPREACL of KNOWLEDGE ON ETHICS
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THE EFFECT OF SPREACL of KNOWLEDGE ON ETHICS

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Publication Date
Tue Jun 01 2021
Journal Name
Int. J. Nonlinear Anal. Appl.
Study of the dual ideal of ku-algebra
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In this work, we apply the notion of a filter of a KU-Algebra and investigate several properties. The paper defined some filters such as strong filter, n-fold filter and P-filter and discussed a few theorems and examples.

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Publication Date
Wed Mar 01 2023
Journal Name
Baghdad Science Journal
Sum of Squares of ‘m’ Consecutive Woodall Numbers
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        This paper discusses the Sums of Squares of “m” consecutive Woodall Numbers. These discussions are made from the definition of Woodall numbers. Also learn the comparability of Woodall numbers and other special numbers. An attempt to communicate the formula for the sums of squares of ‘m’ Woodall numbers and its matrix form are discussed. Further, this study expresses some more correlations between Woodall numbers and other special numbers.

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Publication Date
Thu Jun 30 2016
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Experimental Study of Thermophysical Properties of TiO2 Nanofluid
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Titanium-dioxide (TiO2) nanoparticles suspended in water, and ethanol based fluids have been prepared using one step method and characterized by scanning electron microscopy (SEM), and UV–visible spectrophotometer. The TiO2 nanoparticles were added to base fluids with different volume concentrations from 0.1% to1.5% by dispersing the synthesized nanoparticles in deionized water and ethanol solutions. The effective thermal conductivity, viscosity and pH of prepared nanofluids at different temperatures from 15 to 30 oC were carried out and investigated. It was observed that the thermal conductivity, pH, and viscosity of nanofluids increases with the increase in TiO2 nanoparticle volume fraction

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Publication Date
Thu Jun 25 2020
Journal Name
International Journal Of Drug Delivery Technology
Development of a Simple Colorimetric Determination of Dexamethasone
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A simple, environmentally benign, cost-effective, and sensitive colorimetric determination for the pharmaceutical drug dexamethasone sodium phosphate (DXP) has been developed by the formation of a colored complex with fluoranil. The process was sensitive and linear over the range 1 to 40 μg/mL, excellent correlation coefficient 0.9989, recovery% 99.80 ± 1.3, limit of detection (LOD) and limit of quantification (LOQ) were 0.23 and 0.9 μg/mL, respectively, and good RSD ~1.63%. The experimental conditions were optimized after an intensive study. The approach was validated statistically for the quantification of the analyte in its pure and/or pharmaceutical form. Despite the proposed approach is selective, it still can be applied for

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Publication Date
Sun Sep 04 2011
Journal Name
Baghdad Science Journal
Determination of bacterial contamination of milk using fluorometry
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The aim of this paper is to determine the feasibility of using fluorometric methods as an indicator for quality and contamination of milk with E.coli bacteria, and selection the suitable wavelength to be used with laser induced auto fluorescence. Three groups of milk samples were used in this study: Fresh pasteurized milk samples, milk samples containing different concentration of E.coli bacteria which were added artificially, and milk samples that were kept in refrigerator for 3-5 days. Thirteen excitation wavelengths were used to get the emission spectra for all milk samples using spectroflourometer .The results showed that the emission spectra at 275nm excitation wavelength gave a good differentiation between these three groups.

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Publication Date
Sat Mar 31 2018
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Kinetics of Thermal Pyrolysis of High-Density Polyethylene
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Thermal pyrolysis kinetics of virgin high-density polyethylene (HDPE) was investigated. Thermal pyrolysis of HDPE was performed using a thermogravimetric analyzer in nitrogen atmosphere under non-isothermal conditions at different heating rates 4, 7, 10 °C/min. First-order decomposition reaction was assumed, and for the kinetic analysis Kissinger-Akahira-Sunose(KAS), Flynn-Wall-Ozawa(FWO) and Coats and Redfern(CR) method were used. The obtained values of  average activation energy by the KAS and FWO methods were equal to137.43 and 141.52 kJ/mol respectively, these values were considered in good agreement, where the  average activation energy value obtained by CR equation methods was slightly different which equal to 153.16 kJ/

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Publication Date
Sun Jan 16 2011
Journal Name
Bayt Alhekma
formations of abstract nouns from groups of goagols
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Abstract The study aimed at reviewing translation theories proposed to address problems in translation studies. To the end, translation theories and their applications were reviewed in different studies with a focus on issues such as critical discourse analysis, cultural specific items and collocation translation.