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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 Mar 01 2012
Journal Name
Journal Of Economics And Administrative Sciences
Comparison study of Information Criteria to determine the order of Autoregressive models
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بهذا البحث نقارن معاييرالمعلومات التقليدية (AIC , SIC, HQ , FPE ) مع معيارمعلومات الانحراف المحور (MDIC) المستعملة لتحديد رتبة انموذج الانحدارالذاتي (AR) للعملية التي تولد البيانات,باستعمال المحاكاة وذلك بتوليد بيانات من عدة نماذج للأنحدارالذاتي,عندما خضوع حد الخطأ للتوزيع الطبيعي بقيم مختلفة لمعلماته

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Publication Date
Wed May 10 2023
Journal Name
Journal Of Planner And Development
Principles of sustainable environmental design in the rehabilitation of the marshes region.
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The Marshlands cover an area of ​​about 24% of the land area of ​​Iraq, which gives it special importance to the country with its resources, resources and human capabilities, and because the conditions of this region are different from other areas environmentally and living necessitates subject to certain design principles achieve sustainable environmental integration to maintain them from For future generations, the idea of ​​research is crystallized by the interest of environmental organizations and urban designers in planning and establishing special laws to exploit the region environmentally, economically and tourism, especially after the current focus of the country's economic revival. T tourism and begin the development

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Publication Date
Thu Jan 18 2024
Journal Name
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Ultrastructure of mice testes affected by orally administered crocin of crocus sativus
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In this study, thirty-two adult male mice were divided into four groups control and experimental treatment groups received crocin at 4, 20, and 100 mg/kg daily for six weeks. In results, testosterone level was increased significantly from 18.5 ng/dl in the control to 49.3 ng/dl in group received crocin at 20 mg/kg. The regular features of seminiferous tubules with increased Sertoli cells have been observed in the 20mg/kg crocin group.  In the group received crocin at 100 mg/kg, many of the seminiferous tubules were atrophic, spermatogenic cells were discontinuous in the same areas while the space among them has been increased, and fewer interstitial tissue between seminiferous tubules were observed. The changes were markedly

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Publication Date
Wed Dec 30 2009
Journal Name
Iraqi Journal Of Physics
Effect of Nanocomposites TiO2 addition on the Dielectric Properties of Epoxy resin
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Sheets of Epoxy (EP) resin with addition of TiO2 of grain size (1.5μm, and 50nm) and weight percentage (1%, 3%, and 5%) were prepared. Discs of 20mm diameter and 3mm thickness were cut for dielectric measurements. Dielectric properties (dielectric constant, dispassion factor and electrical conductivity) over the frequency range 102 -106 Hz were measured.
Comparison was made between the effect of micro and nano particles of TiO2 on the dielectric properties of EP composites with different weight percentage. Epoxy composites with micro sized particles of TiO2 were observed to have the better values of dielectric properties.

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Publication Date
Fri Jun 01 2018
Journal Name
Journal Of Legal Sciences
Compensation for Victims of Technological Risks in the Scope of Medical Practice
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those affected by technological development risks within the scope of medical works. The unprecedented technological development the world witnesses nowadays has been providing brilliant medical service to the human being including examination, diagnosis and the treatment or follow up. However, such works hide behind potential risks threatening people's lives and such risks my be discovered within the limits of now – how and technical knowledge prevailing the time of rendering the medical service. Also this the question is raised on how to keep up between the safety of the patients and such risks are being unknown by the provider and questioning them contradicts the justices. subsequently, can the patients (affected) acquire the compensat

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Publication Date
Fri May 01 2020
Journal Name
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Semi-Analytical Prediction of Flank Tool Wear in Orthogonal Cutting of Aluminum
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This study aims to model the flank wear prediction equation in metal cutting, depending on the workpiece material properties and almost cutting conditions. A new method of energy transferred solution between the cutting tool and workpiece was introduced through the flow stress of chip formation by using the Johnson-Cook model. To investigate this model, an orthogonal cutting test coupled with finite element analysis was carried out to solve this model and finding a wear coefficient of cutting 6061-T6 aluminum and the given carbide tool.

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Publication Date
Thu Apr 01 2021
Journal Name
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Tourist development of heritage in Algeria: case of the Hypone site -ANNABA-
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Publication Date
Wed Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Effect of Some Storage Conditions upon the Survival of Some Fungal Spores
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Folic acid and multivitamin tablets containing Aspergillus flavus Penicillia spp. and Cladosporia spores were prepared at a compression pressure of 148 MN/m2 and stored at 35°C under different relative  humidifies (75,85, and 95)% within air tight containers, to study the effect of storage condition on them, as well as ,the estimation of the microbial level of the raw materials intended to be used in the two kinds of tablets . Result showed that some raw materials derived from natural origin were heavily contaminated with microorganism compared to that of synthetic origin ,the results also indicated the effect of relative humidity , types of fungal spore , and the hygroscopic nature of exicpient upon survival. Multivit

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Publication Date
Tue Jul 11 2023
Journal Name
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The Relationship of Digital Skills with the Professional Competence of Kindergarten Teachers
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The current research aims to identify the level of digital skills of kindergarten teachers, identify the level of professional competence of kindergarten teachers, as well as to identify the relationship between digital skills and the professional competence of kindergarten teachers. The current research was determined by kindergarten teachers in the second Baghdad / Karkh Education Directorate for the academic year (2021-2022). The research sample consisted of (100) teachers chosen in a simple random way. To achieve the objectives of the research, the researcher developed a digital skills scale of (20) items and a scale of professional competence consisting of (22) items. The results revealed that kindergarten teachers have a high level

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Publication Date
Fri May 01 2015
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Comparison of in vivo uptake of radioactive gold nanoparticles formulated using phytochemicals
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