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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
Thu Jan 01 2015
Journal Name
Journal Of Nanomaterials
Comparative Studies on Thermal Performance of Conic Cut Twist Tape Inserts with SiO<sub>2</sub>and TiO<sub>2</sub>Nanofluids
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This paper presents a comparison study on thermal performance conic cut twist tape inserts in laminar flow of nanofluids through a constant heat fluxed tube. Three tape configurations, namely, quadrant cut twisted tape (QCT), parabolic half cut twisted tape (PCT), and triangular cut twisted (VCT) of twist ratioy= 2.93 and cut depthde= 0.5 cm were used with 1% and 2% volume concentration of SiO2/water and TiO

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Publication Date
Mon Aug 19 2024
Journal Name
Chemical Papers
In vitro and in silico evaluation of 4'-hydroxy-[1,1'-biphenyl]-4-carbohydrazide Schiff base and oxadiazole derivatives targeting EGFR allosteric site
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Publication Date
Fri Jul 01 2022
Journal Name
Iranian Journal Of Neonatology
Maternal Risk Factors and Outcomes of Premature Neonates Admitted to the Neonatal Care Unit in AlElwiya Pediatric Teaching Hospital in Baghdad, Iraq
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Background: Prematurity and its complications are the major causes of neonatal and infant morbidity and mortality. Although the cause of preterm labor is often unknown, numerous etiological risk factors may be implicated. To identify the risk factors that lead to prematurity and assess the neonatal outcomes that preterm neonates may develop. Methods: This case-control study was conducted at AL-Elwiya Pediatric Teaching Hospital, Baghdad, Iraq, from the 1st of June to the 31st of December 2019. A non-randomized sample of 700 neonates admitted to the neonatal care unit was included in this study and divided into two groups of preterm full-term neonates as the experimental and control groups, respectively (n=350 each). The same questionnaire w

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Publication Date
Fri Oct 02 2020
Journal Name
Biochem. Cell. Arch.
MORPHOLOGICAL DESCRIPTION AND COMPARATIVE HISTOLOGICAL STUDY OF THE LIVER IN TWO IRAQI MAMMALS : WEASEL (HERPESTES JAVANICUS) AND EASTERN GRAY SQUIRREL (SCIURUS CAROLINENSIS
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The results of the current study showed that the liver of H. javanicus appeared as large lobulated organ divided into six distinct lobes, that filled the cranial region and little extended to the middle region of abdominal cavity. On the other hand, liver of S. carolinensis laid against the diaphragm, occupied the cranial region of the abdominal cavity and consisted of five lobes. The liver is surrounded with a thin capsule of dense regular collagenous connective tissue and few numbers of smooth muscles fibers can be seen in the capsule that covered the squirrel liver. The liver parenchyma divided into a large number of interconnected hepatic lobules marked only by the abundant amount of connective tissue bordered the triads, and within the

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Publication Date
Sun Nov 01 2015
Journal Name
Journal
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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KE Sharquie, AA Noaimi, BAM Saleh, 2015

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Publication Date
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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Publication Date
Sat Aug 12 2017
Journal Name
Journal Of Engineering
Prepare rules spatial data for soils and the Calculation of an Area in Iraq for Industrial Purposes using Geographic Information Systems (GIS)
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      The process of soil classification in Iraq for industrial purposes is important topics that need to be extensive and specialized studies. In order for the advancement of reality service and industrial in our dear country, that a lot of scientific research touched upon the soil classification in the agricultural, commercial and other fields. No source and research can be found that touched upon the classification of land for industrial purposes directly. In this research specialized programs have been used such as geographic information system software The geographical information system permits the study of local distribution of phenomena, activities and the aims that can be determined in the loca

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Publication Date
Fri Dec 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
Comparing the Sequential Nonlinear least squared Method and Sequential robust M method to estimate the parameters of Two Dimensional sinusoidal signal model:
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Estimation of the unknown parameters in 2-D sinusoidal signal model can be considered as important and difficult problem. Due to the difficulty to find estimate of all the parameters of this type of models at the same time, we propose sequential non-liner least squares method and sequential robust  M method after their development through the use of sequential  approach in the estimate suggested by Prasad et al to estimate unknown frequencies and amplitudes for the 2-D sinusoidal compounds but depending on Downhill Simplex Algorithm in solving non-linear equations for the purpose of obtaining non-linear parameters estimation which represents frequencies and then use of least squares formula to estimate

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Publication Date
Wed May 19 2010
Journal Name
Journal Of College Of Science, University Of Babylon
H-Point Standard Addition Method for Simultaneous Determination of Cimetidine and Erythromycin Ethylsuccinate Drugs Using Bromothymol Blue as a Chromogenic Complexing Agent
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The H-Point Standard Addition Method (H-PSAM) has been applied for spectrophotometric simultaneous determination of Cimetidine and Erythromycin ethylsuccinate using Bromothymol Blue (BTB) as a chromogenic complexing agent in a buffer solution at pH 5.5.

Publication Date
Tue Oct 01 2013
Journal Name
Journal Of Economics And Administrative Sciences
The Relationship Between The Internal Marketing and Quality Services : a Filed Study on Samples of Customers and Employees In Iraqi Commercial Banks
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Abstract

The Paper highlights on one of the main activities in marketing management. That is the internal marketing in the commercial banks and its relationship with the quality services offered to satisfy customers needs and wishes in order to reach he ultimate objectives of those banks. Two state and five private banks in Basrah city (Iraq) were taken in a field study. The survey covered the opinions of (184) state bank employees and (158) clients . The analysis of the survey shows that there is a strong relationship between the internal marketing ( in the banks covered by the survey) and the quality of banking objective services and the private banks show greater interest and concern to the internal ma

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