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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
Tue Oct 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
Achieving Educational Service Quality by applying international standard (ISO21001:2018) case study / university of technology – electromechanical engineering department – energy branch
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The research examines the mechanism of application of )ISO 21001: 2018( in the Energy Branch- Electromechanical Engineering at the University of Technology to achieve the quality of the educational service to prepare the branch to obtain the certificate of conformity with the requirements of) ISO 21001: 2018(, the necessary data were collected Depending on the (CHEKLIST) of (ISO 21001: 2018), field interviews and records of the concerned department, The researchers reached a number of results, the most prominent of which was the adoption of high quality leadership leaders and their willingness to implement the standard requirements, The university has a basic structure that qualifies it to implement the international standard, as

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Publication Date
Fri Dec 01 2023
Journal Name
Iraqi Journal Of Physics
Eco-Friendly Synthesis of Ag-ZnO Nanocomposite Using Aloe-vera, Hibiscus Sabdariffa Plants and Their Antibacterial and Anti-fungi Activities
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The current study used extracts from the aloe vera (AV) plant and the hibiscus sabdariffa flower to make Ag-ZnO nanoparticles (NPs) and Ag-ZnO nanocomposites (NCs). Ag/ZnO NCs were compared to Ag NPs and ZnO NPs. They exhibited unique properties against bacteria and fungi that aren't present in either of the individual parts. The Ag-ZnO NCs from AV showed the best performance against E. coli, with an inhibition zone of up to 27 mm, compared to the other samples. The maximum absorbance peaks were observed at 431 nm and 410 nm for Ag NPs, at 374 nm and 377 nm for ZnO NPs and at 384 nm and 391 nm for Ag-ZnO NCs using AV leaf extract and hibiscus sabdariffa flower extract, respectively. Using field emission-scanning electron microscopes (FE-

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Publication Date
Mon Mar 15 2021
Journal Name
Al-academy
Anthropology and Representations of Magic in Arab Theatrical Text Harut and Marut's Play as a Model: وصال خلفة كاظم البكري
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The research (Anthropology and Representations of magic in Arab Theatrical Text, Harut and Marut's play as a Model) is concerned with studying magic and the forms of its presence in the theatrical text in different human cultures where it belongs. The research consists of four chapters.
The first chapter includes the research problem that revolves around the following questions: (what is the mechanism of employing magic anthropology and its representations in the Arab theatrical text Harut and Marut's play as a model?), and the research importance which is attributed to the necessity of studying (magic) in the Arab theatrical text as it is considered the inauguration of one of the social phenomena that many researchers in the field o

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Publication Date
Sun Mar 20 2016
Journal Name
Al-academy
The mechanism of addition and subtraction in the industrial product and its relation to employment pressure: بـــان محمد شـاكر الطائي
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The Significance of this research comes as a result of the development occurring in various life fields including the field of technical and technological development in the domain of industrial products which are in direct touch with the receiver, and because the study of deletion and addition mechanism didn't Find the Scientific space through researches and Studies. On this basis , the aim of this study is defining the forms of deletion and addition mechanism in designing the industrial product in a way that fits the functional presser . As to the limitations of this study, they involve examples of readymade Turkish House furniture, which is available in Iraqi local markets in Baghdad city 2013. The study included four chapters. The fi

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Publication Date
Fri Jul 14 2023
Journal Name
International Journal Of Information Technology & Decision Making
A Decision Modeling Approach for Data Acquisition Systems of the Vehicle Industry Based on Interval-Valued Linear Diophantine Fuzzy Set
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Modeling data acquisition systems (DASs) can support the vehicle industry in the development and design of sophisticated driver assistance systems. Modeling DASs on the basis of multiple criteria is considered as a multicriteria decision-making (MCDM) problem. Although literature reviews have provided models for DASs, the issue of imprecise, unclear, and ambiguous information remains unresolved. Compared with existing MCDM methods, the robustness of the fuzzy decision by opinion score method II (FDOSM II) and fuzzy weighted with zero inconsistency II (FWZIC II) is demonstrated for modeling the DASs. However, these methods are implemented in an intuitionistic fuzzy set environment that restricts the ability of experts to provide mem

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Publication Date
Tue Sep 01 2015
Journal Name
Photomedicine And Laser Surgery
Evaluation of Temperature Elevation During Root Canal Treatment with Dual Wavelength Laser: 2780 nm Er,Cr:YSGG and 940 nm Diode
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Publication Date
Thu Feb 16 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Cost-effectiveness Analysis of Reference Infliximab (Remicade) Compared to its Biosimilar (Remsima) in Iraqi Patients with Rheumatoid Arthritis (Conference Paper )#
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The study objective was to conduct Pharmacoeconomics study (cost-effective analysis) between infliximab reference (Remicade) and its biosimilar (Remsima) in patients with rheumatoid arthritis (RA) in Iraqi hospitals.

This is a retrospective multicenter pharmacoeconomic analysis conducted at two large teaching governmental hospitals in Baghdad, Iraq which provided infliximab to patients with RA. Data were collected from patient’s medical records and face-to-face interviews with the patients from December 2021 to April 2022.

The study included 57 patients with rheumatoid arthritis (RA).  The patients were categorized into two groups according to the type of infliximab they received over 30 weeks: 27 patients received

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Publication Date
Sun Dec 01 2024
Journal Name
Journal Of Ecological Engineering
Asphalt Binder Modification with High-Density Polyethylene Polymer and Low-Density Polyethylene Polymer – Efficiency of Conducting Semi-Wet Mixing Process
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In this research, the performance of asphalt mixtures modified with polyethylene polymer (PE) by adding 2%, 4%, and 6% percentages was evaluated. Two kinds of PE are employed: Low-Density PE (LDPE) and High-Density PE (HDPE). The semi-wet mixing technique (SWM) was conducted to avoid stability issue for PE-modified binder during storage condition. Many experimental tests were conducted to evaluate the ability of these mixtures to withstand the effects of loads and moisture. The hardness index of these mixtures was also measured to determine their resistance to the effects of high temperatures without causing permanent deformations. The results showed that adding PE led to a remarkable enhancement in the performance of PE-modified mixtures.

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Publication Date
Fri Jan 10 2025
Journal Name
Chemchemtech
LC-MS/MS METHOD FOR THE DETERMINATION OF IMATINIB MESYLATE IN BLOOD PLASMA SAMPLES AFTER ADSORPTION BY COPPER TANNIC ACID
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A novel metal-organic framework (MOF) sorbent based on tannic acid/copper (TA/Cu) was synthesized and characterized for the application of the anticancer drug imatinib (IMA) from biological samples. The TA/Cu MOF was prepared via a facile coordination reaction and thoroughly characterized by SEM, XRD, and FTIR techniques. Critical parameters influencing the extraction efficiency of imatinib mesylate (IMAM), including pH, ionic strength, desorption solvent, and adsorption-desorption time were optimized. With acetonitrile as the desorption solvent, the method demonstrated a broad linear range of 0.55-300 μg L-1 under ideal conditions. Limits of detection and quantification were found to be 0.16 μg L-1 and 0.55 μg L-1, respectively.

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Publication Date
Sun Dec 01 2019
Journal Name
Regenerative Therapy
In vitro periodontal ligament cell expansion by co-culture method and formation of multi-layered periodontal ligament-derived cell sheets
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Objective: Per-implantitis is one of the implant treatment complications. Dentists have failed to restore damaged periodontium by using conventional therapies. Tissue engineering (stem cells, scaffold and growth factors) aims to reconstruct natural tissues. The paper aimed to isolate both periodontal ligament stem cells (PDLSCs) and bone marrow mesenchymal stem cells (BMMSCs) and use them in a co-culture method to create three-layered cell sheets for reconstructing natural periodontal ligament (PDL) tissue. Materials and methods: BMMSCs were isolated from rabbit tibia and femur, and PDLSC culture was established from the lower right incisor. The cells were co-cultured to induce BMMSC differentiation into PDL cells. Cell morphology, stem cel

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