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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 Jun 15 2021
Journal Name
Al-academy
The treatment of the output of Marquez novels in the international cinema … Love in the time of cholera: منهل باسم سعيد الطاهر
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Gabriel Garcia Marquez, the Nobel laureate of literature in 1982, is one of the most famous Latin American writers who have been distinguished by the magic of realism. We can say the months in the world and he is almost the most controversial for many reasons and for these reasons he did not accept that his novels turn into movies Marquez agreed to turn one of his most important and most beautiful novels, "Love in the Time of Cholera," which he wrote in 1985 and agreed to convert to a film in 2006 after the novel was bought by the author for $ 3 million. Mike Noel to bring out

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Publication Date
Fri Apr 01 2016
Journal Name
Journal Of Economics And Administrative Sciences
THE USE OF SIMULATION AND LINEAR PROGRAMMING IN THE PLANNING OF AUDIT WORK (An Empirical Study in the Office of Financial Supervision)
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Research includes three axes, the first is the average estimate time of achievement (day) to work oversight, to five supervisory departments in the Office of Financial Supervision Federal and then choose the three control outputs and at the level of each of the five departments above, and after analyzing the data statistically back to us that the distribution of the times of achievement It is the exponential distribution (Exponential Distribution) a parameter (q), and the distribution of normal (Normal Distribution) with two parameters (μ, σ2), and introduced four methods of parameter estimation (q) as well as four modalities parameter to estimate (

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Publication Date
Thu Jun 22 2017
Journal Name
Research Journal Of Pharmaceutical, Biological And Chemical Sciences
Testing the Efficiency of Probiotic in Reducing the Growth of Aspergillus flavas in Corn Stored and its Effect on Performance of Broiler
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This study has been done for testing the effectiveness and efficiency of probiotic in its ability to inhibit Aspergillus flavus , which secretes the aflatoxin B1 and compare it with materials that were approved to be effective in the inhibition of the growth of fungi and break down and reduction of mycotoxin. these are the filax substance and ozone gas. A laboratory experiment has been conducted to determine the isolates out of the fungus producing the aflatoxin B1.the isolate producing aflatoxin B1 has grown on the yellow corn seed. the probiotic was added along with the filax and they have been exposed to ozone gas and then they were stored from 30 days. A bio test was con conducted to knw the effects of biological toxin on the broiler me

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Publication Date
Thu May 12 2022
Journal Name
Journal Of Kerbala For Agricultural Sciences
Response of Bread Wheat Crop to the Spray of Alcoholic Sugars and A balanced Mineral Fertilizer in the Central Region of Iraq
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Two field experiments were conducted during the season 2021-2022 in central Iraq represented by the Al-Muthanna governorate - Al-Majd District and Al-Qadisiyah governorate / Al-Nouriah Research Station to determine the productivity of the Baghdad 3 cultivar from spray foliar fertilization of Macro and Micro elements with alcoholic sugars and half the fertilizer recommendation for addition floor, three treatments were used for fertilization: T1 as the control treatment and T2 with alcoholic sugar fertilization at a concentration of 20 g.L-1 + the fertilizer combination of Macro and Micro elements, and T3 with alcoholic sugar fertilization at a concentration of 40 g.L-1 + the fertilizer combination of Macro and Microelements, at irrigation 55

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Publication Date
Thu Mar 01 2012
Journal Name
Journal Of Economics And Administrative Sciences
Analysis of the relationship between the degree of economic freedom and foreign trade of selected developing countries for the period (1990-2005) *
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Is a high degree of economic freedom an important part in the development of the economies of developing countries in the last decade of the twentieth century and the beginning of the twentieth century and the atheist. This is because a test subject (deltoid analysis of the relationship between the degree of economic freedom and foreign trade of selected developing countries for the period
( 1990 -2005) to determine the degree of economic freedom in foreign trade promotion in Singapore and Turkey. The research recommends a number of  recommendations, the most important is the responsibility of the Ministry of Planning in Iraq that is providing the necessary data for the Fraser Institute, the aim of increasing cooperation

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Publication Date
Thu Apr 18 2019
Journal Name
Al-kindy College Medical Journal
Seroprevalence of Immunoglobulin G (IgG) and Immunoglobulin M (IgM) and Risk Factors of Toxoplasmosis for A sample of Pregnant Women in Baghdad
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Background: Toxoplasmosis is a very common infection caused by the obligate intracellular protozoan parasite. This parasite is called Toxoplasma gondii widely distributed around the world . Toxoplasma gondii can be vertically transmitted to the fetus during pregnancy and may cause wide range of clinical manifestations in the offspring.

Objective: To determine seroprevalence Immunoglobulin G (IgG) and Immunoglobulin M  (IgM ) to toxoplasma gondii among pregnant women and to identify the risk factors.

Type of the study: A cross-sectional study.

Methods: A total of 110 blood samples of pregnant women were collected from

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Publication Date
Wed Mar 02 2022
Journal Name
International Journal Of Early Childhood Special Education
Understanding the life applications of green chemistry among students of the College of Education for Pure Sciences, Ibn al-Haytham in Iraq
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Publication Date
Wed Jul 15 2020
Journal Name
Plant Archives
EFFECT OF USING OF CHLORELLA ALGAE (CHLORELLA VULGARIS) IN LAYER DIETS ON PRODUCTION PERFORMANCE AND LACTOBACILLUS COUNT IN THE INTESTINE OF HENS
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This study was conducted at the Poultry Research Station in Abu Ghraib, Department of Agricultural Research, Ministry of Agriculture, the experimental field during three months (Three terms for a period of four weeks), from 10 th of December 2019 to the 10 th of January 2020. The study aimed to determine the effect of using different proportions of chlorella algae in layer hen ration and its effect on the hen's productive performance and numbers of lactobacilli bacteria in the intestine. The experiment included 400 laying hens (ISA Brown) of 54 week old which were fed according to the standard requirements mentioned in the guide for this breed (ISA Brown layer management guide). The hens raised using a 3 stage cages system with five hens in

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Publication Date
Thu Jan 04 2024
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Reflection of the Adoption and Application of the Financial Reporting Standard (IFRS16) on the Financial Performance of the General Iraqi Insurance Company
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Abstract

                 The study aims to clarify the impact of the adoption of the International Financial Reporting Standard (IFRS16) on lease contracts in the General Iraqi Insurance Company on the financial statements, and thus the impact on financial ratios and indicators, Since the financial reporting standard considers lease contracts as an asset called the right to use the asset and is offset by a liability, this changes the way the financial statements are presented, with an addition to both the asset and liability sides. In order to show the extent to which the adoption of the standard reflects on the financial performance

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Publication Date
Tue Jan 01 2019
Journal Name
Biochemical & Cellular Archives
Assessment of uric acid in patients of end-stage renal disease with hypertension and diabetic nephropathy and the risk of cardiovascular diseases
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The relationship of hyperuricemia to kidney disease, diabetes, hypertension and the risk of cardiovascular diseases remain controversial. The aim of this study is to evaluate the use of uric acid (UA) levels to find the higher risk of cardiovascular disease (CVD) in patients with end stage renal disease that have diabetic nephropathy (DN), nephropathy with hypertension (NH) and patients with both diabetic nephropathy with hypertension (DNH). This study deals with 115 patients with end-stage renal disease under hemodialysis sub-grouped into 35 patients with (DN), 40 patients with (NH), and 40 patients with (DNH). Some biochemical parameters were determined in the serum of all participants such as HbA1c, fasting blood glucose (FBG), UA, urea,

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