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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
Sun Jun 01 2014
Journal Name
Baghdad Science Journal
Determination of total phenol, antioxidant and antimicrobial activities of Avena sativa and Ocimum basilicum
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The present study investigated the total content of phenolic compounds, antioxidant and antimicrobial activities of water extracts oat (Avena sativa) and basil (Ocimum basilicum), medicinal plants. The Folin-ciocalteu reagent assay was used to estimate the total phenolic content of plants extract. The antioxidant capacity of the plants extract was tested by ferric reducing/antioxidant power Assay (FRAP) and ferric reducing scavenging activity using DPPH method, and the antimicrobial activity was measured against [Staphylococcus epidermidis; Staphylococcus aureus; Proteus spp.; Klebsiella spp.; Escherichia coli; Candida albicans] as tester strains. The total phenolic content of Avena sativa and Ocimum basilicum extracts revealed that the

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Publication Date
Thu Dec 30 2021
Journal Name
Al-kindy College Medical Journal
Impact of different sources of noise exposure on hearing impairment: A cross- sectional study
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Background: Mental health is integrated into PHC as a strategy of WHO to fill the gap in mental health treatment. Part of this strategy needs a level of task shifting so that mental health care is provided by different level of PHC workers and not only specialists such as psychiatrists and psychologists.

Objectives: To assess the knowledge and attitudes of family doctors regarding the provision of psychological health in PHCC and if there is an association between the certificates of these family doctors and their Knowledge and attitudes to psychological health.

Subjects and Methods:  A cross-sectional descriptive study with analytic elements was conducted in 8 famil

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Publication Date
Sun Sep 11 2022
Journal Name
Journal Of Petroleum Research And Studies
Distribution of Petrophysical Properties Based on Conceptual Facies Model, Mishrif Reservoir/South of Iraq
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A 3D geological model is an essential step to reveal reservoir heterogeneity and reservoir properties distribution. In the present study, a three-dimensional geological model for the Mishrif reservoir was built based on data obtained from seven wells and core data. The methodology includes building a 3D grid and populating it with petrophysical properties such as (facies, porosity, water saturation, and net to gross ratio). The structural model was built based on a base contour map obtained from 2D seismic interpretation along with well tops from seven wells. A simple grid method was used to build the structural framework with 234x278x91 grid cells in the X, Y, and Z directions, respectively, with lengths equal to 150 meters. The to

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Publication Date
Tue Dec 20 2022
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
ECOLOGY OF LEECHES AND GASTROPODS OF THE LOWER AK-BUURA RIVER, FERGANA VALLEY,UZBEKISTAN
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This study was conducted on species composition, morphology, ecological characteristics, biotope distribution, ecological groups, biodiversity indicators and zoogeography of leeches and gastropods distributed in the lower Ak-Buura River. According to the results, it was found that 7 species of leeches belonging to 4 families and 6 genera and 10 species of fresh-water gastropods belonging to 3 families and 6 genera live in the lower Ak-Buura River. In the river, it was observed that leeches are mainly distributed in muddy biotopes, and gastropods are widespread in muddy, stony and sandy biotopes with a lot of plants. Biodiversity indices of leeches and gastropods in the Ak-Buura River were analyzed using the Shannon index. As a result, it

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Publication Date
Fri May 10 2024
Journal Name
South Asian Research Journal Of Biology And Applied Biosciences
The Effect of Human Leukocyte Antigen in Development of Systemic Lupus Erythematosus in Patients
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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies against nuclear antigens and a systemic inflammation that can damage a broad spectrum of organs. SLE patients suffer from a wide variety of symptoms, which can affect virtually almost any tissue. As lupus is difficult to diagnose, the worldwide prevalence of SLE can only be roughly estimated to range from 10 and 200 cases per 100,000 individuals with dramatic differences depending on gender, ethnicity, and location. Although the treatment of this disease has been significantly ameliorated by new therapies, improved conventional drug therapy options, and a trained expert eye, the underlying pathogenesis of lupus still

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Publication Date
Mon Jun 01 2009
Journal Name
Journal Of Economics And Administrative Sciences
The role of Zakat in supporting and stimulating the flow of consumption and investment
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الزكاة فريضة من فرائض الإسلام وعبادة من العبادات التي اقرها الشرع الإسلامي هذه الفريضة المالية التعبدية بالإضافة الى دورها المعنوي الذي يهدف الى إرساء قواعد العدالة الاجتماعية والقضاء على مشكلة الفقر في المجتمع الاسلامي وكما ينص عليها الدين الإسلامي فان لها ابعادها ووظائفها الكثيرة التي تخدم اليات العمل الاقتصادي في مجتمع يعمل وفق نظام اقتصادي أسلامي .

ان انفاق الاموال المتحصلة من فريض

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Publication Date
Sun Jun 04 2017
Journal Name
Baghdad Science Journal
The efficiency of some plant extracts for growth inhibition of Candida albicans and Trichophytonmentagrophytes
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Plant extracts occupied a big place in diseases treatment and preserving human health because, they contain many active substances that can be exploited in the field of pharmaceutical manufacturing from natural materials. Therefore, this study was conducted to evaluate the effect of different concentrations of plant extracts for each of Nigella sativa, Alliumsativum and Allium cepa against the fungal growth of Candida albicans that cause many skin diseases and infections to humans as well as Trichophyton mentagrophytes, which affects the hair, skin and nails. These two fungi have been isolated and diagnosed from people who have skin infection. Both fungal isolates were treated with extracts of Nigella sativa, Alliumsativum and Allium cepa

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Publication Date
Wed Jan 01 2020
Journal Name
Iop Conference Series: Materials Science And Engineering
Influence of CFRP Strengthening on the Behavior of Concavely-Curved Soffit Concrete Bridge Girders
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Abstract<p>Over the last few decades, fiber reinforced polymer (FRP) has been increasingly used in strengthening different structural concrete members. The main objective of this research is to study the influence of curvature on the performance of curved soffit reinforced concrete (RC) bridge girders that have been strengthened with carbon fiber reinforced polymers (CFRP). This experimental program was designed to evaluate the effect of concavity and soffit curvature on the CFRP laminate utilization and load capacity, compared to flat soffit RC beams strengthened with the same CFRP system. Accordingly, five beams, 2.7 m in length and having the same degree of soffit curvature (20 mm per 1 meter</p> ... Show More
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Publication Date
Thu Dec 04 2014
Journal Name
Engineering And Technology Journal
Optimization of the Time Required for Determination of the Total Dissolved Salts in Soil ‫
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Publication Date
Sun Sep 06 2009
Journal Name
Baghdad Science Journal
Extension of the Chebyshev Method of Quassi-Linear Parabolic P.D.E.S With Mixed Boundary Conditions
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The researcher [1-10] proposed a method for computing the numerical solution to quasi-linear parabolic p.d.e.s using a Chebyshev method. The purpose of this paper is to extend the method to problems with mixed boundary conditions. An error analysis for the linear problem is given and a global element Chebyshev method is described. A comparison of various chebyshev methods is made by applying them to two-point eigenproblems. It is shown by analysis and numerical examples that the approach used to derive the generalized Chebyshev method is comparable, in terms of the accuracy obtained, with existing Chebyshev methods.

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