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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
Wed Jan 01 2020
Journal Name
Medical Journal Of Babylon
Diagnostic value of neutrophil lymphocyte ratio in detection of acute appendicitis
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The diagnosis of acute appendicitis (AA) sometimes is illusive and the accompanying clinical and laboratory manifestations cannot be used for definitive diagnosis. Objective: This study aimed to evaluate the diagnostic value of neutrophil/lymphocyte ratio (NLR) in detection of AA. Materials and Methods: This is a cross-sectional study that included a total of 80 adult patients with AA and 62 age- and gender-matched patients with abdominal pain due to causes other than AA. Three milliliter of peripheral blood were collected from each participant. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. Receiver operating characteristic curve was used to assess the diagnostic value of NLR in detection

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Sun Dec 12 2010
Journal Name
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A documentary study of natural resources and ways of protecting them
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The problem of research is that there are ways to protect and sustain environmentally important sites in Iraq. There are no documentary sources for these sites, such as the natural landscape of natural and important natural resources, which suffer from severe environmental neglect

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EMPLOYMENT OF NON-CONVENTIONAL MATERIAL IN PURIFICATION OF CONTAMINATED AQUEOUS SOLUTIONS
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In this study, the ability of pistachio shells, as an unconventional adsorbent, to recover thallium cations from contaminated aqueous solutions was investigated. To achieve the objective of the study, practical experiments were conducted using a batch-mode adsorption unit under various operating conditions. The results obtained showed that the pistachio shells have the ability to remove thallium cations with a high efficiency exceeding 86% at room temperature. The results indicated that the maximum treatment efficiency was achieved at values of 7, 350 rpm, 86 ppm, 5 g, 150 min of pH, agitation speed, initial concentration of thallium, dosage of pistachio shell used, and contact time, respectively. Morphological results confirmed tha

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Tue Sep 01 2009
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Study Effect of Dezincification on the Fatigue Properties of Brass Alloy
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This research includes a study of dezincification by corrosion from brass alloys in three types of media, which are acidic solution, basic and slat solution in different percentages. The study show the higher dezincification occurs in basic solution which decrease the fatigue properties where the fatigue properties are inversely proportional with dezincification.

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Publication Date
Wed Jan 01 2020
Journal Name
Corporate Ownership And Control
Planning and controlling of intellectual capital: The role of beyond budgeting
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The purpose of this study is to explore whether the adoption of Beyond Budgeting (BB) as a management accounting practice (MAP) contributes to developing intellectual capital (IC) and creating value in Iraqi companies. This requires an understanding of the views of the Iraqi managers about the nature of the information provided by this practice, which may be used to determine whether this information is relevant in the management of IC in the context of Iraq. This research aims also to explore the challenges of the adoption of the BB in planning and controlling IC in Iraq. The study adopts a qualitative approach and an interpretive paradigm. It also adopts a semi-structured interview method of collecting data from executive managers

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Publication Date
Thu May 18 2023
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Numerical Study Of Heat Transfer In Cooling Passages Of Turbine Blade
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As the temperature of combustion gases is higher than the melting temperature of the turbine materials, cooling of turbine parts in a gas turbine engine is necessary for safe operation. Cooling methods investigated in this computational study included cooling flow losses. Film-cooling is one typically used cooling method whereby coolant is supplied through holes passage, in present study the holes placed along the camber line of the blade. The subject of this paper is to evaluate the heat transfer that occur on the holes of blade through different
blowing coolant rates. The cases of this study were performed in a low speed wind tunnel with two tip gap at small and large (0.03 and 0.09cm) and multiple coolant flow rates through the fil

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Thu Dec 15 2022
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Formulation and Characterization of Oleogel as a Topical Carrier of Azithromycin
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This study aims to formulate azithromycin oleogel to locally treat skin infections such as acne vulgaris and skin wound infection. Providing a form of azithromycin that can be administered topically is highly desired to prevent unwanted systemic complications including diarrhea, nausea, and abdominal pain. Additionally, it will avoid first pass metabolism, improves patient acceptance, provides an alternative in nauseated patients, decreases the dose by direct contact with the pathological site, and provides a noninvasive and convenient mode of administration. Furthermore, for treating wound infections, the gel will act as a scaffold biomaterial for wound closure besides its antibacterial effect. Herein, we propose the use of grapeseed oil-b

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Thu Sep 12 2019
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Reliability of fine needle aspiration biopsy in diagnosis of breast lump
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Background: breast cancer is commonest cancer globally and the 1st cancer in Iraq among females, its management and prognosis depend on early diagnosis, the traditional method was excisional biopsy which is expensive and invasive leading to delayed diagnosis, FNAB is cheap nom invasive more acceptable to women, Aim of the study: to test the reliability of FNAB in preoperative diagnosis of breast lump.

Methodology: This is a retrospective study of 204 cases, 102 breast cancer cases and 102 benign breast lesions, taken between Jan. 2017 – Nov. 2017. The sample taken from the breast cancer early detection center in  Al-Alwiyaa maternity teaching hospital, during the year 2017

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Sun Mar 13 2011
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Publication Date
Thu Jul 01 2010
Journal Name
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FOUR NEW SPECIES OF THRIPS (THYSANOPTERA: THRIPIDAE) FROM MIDDLE OF IRAQ
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