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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 May 24 2023
Journal Name
College Of Islamic Sciences
Analyzing the likeness of fundamentalists and examples of its jurisprudential applications
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The new events in every era are endless, and it is not required of the legal texts to pursue each event by itself and attach to it its ruling.
At the same time, every event or action must have a Shari’a ruling according to the wise Lawgiver, and our scholars have noted this in every event presented to them. ...etc.
It is well known that reaching the legal ruling on a matter, by examining the detailed evidence, is subject to following the path of the rules and regulations specific to the overall evidence, which we organize on the basis of the principles of jurisprudence.
Therefore, any disagreement about the manner or content of these rules will have an impact on the difference of jurists in partial issues, when examining the d

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Publication Date
Thu Jan 30 2020
Journal Name
Al-kindy College Medical Journal
Role of Loop Ileostomy in the Management of Ulcerative Colitis Patients
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Background: Ulcerative colitis is a chronic inflammatory condition characterized by relapsing and remitting episodes of inflammation limited to the mucosal layer of the colon.Loop ileostomy might be helpful in the management of the disease.

Objective: To evaluate the role of loop ileostomy in the management of ulcerative colitis.

 Methods: Between Januarys 2008 and January 2018, patients with fulminant ulcerative colitis resistant to medical therapy had been referred to our surgical unit and were included in our study. Assessment of the patients’ medical status (serum electrolytes, total serum protein, complete blood count, erythrocyte sedimentation rate, general stool exam,and abdominal ultrasound

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Publication Date
Fri May 31 2019
Journal Name
Journal Of Engineering
Geological Model of the Tight Reservoir (Sadi Reservoir-Southern of Iraq)
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A3D geological model was constructed for Al-Sadi reservoir/ Halfaya Oil Field which is discovered in 1976 and located 35 km from Amara city, southern of Iraq towards the Iraqi/ Iranian borders.

Petrel 2014 was used to build the geological model. This model was created depending on the available information about the reservoir under study such as 2D seismic map, top and bottom of wells, geological data & well log analysis (CPI). However, the reservoir was sub-divided into 132x117x80 grid cells in the X, Y&Z directions respectively, in order to well represent the entire Al-Sadi reservoir.

Well log interpretation (CPI) and core data for the existing 6 wells were the basis of the petrophysical model (

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Publication Date
Sat Jun 01 2019
Journal Name
The Iraqi Postgraduate Medical Journal
Results of Minimal Dosage Propranolol in the Management of Infantile Haemangioma
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ABSTRACT: BACKGROUND: Infantile haemangioma one of the most common tumour of new borns , a safe and effective treatment options are under ongoing research . OBJECTIVE: The authors show the effectiveness and safety of low dose propranolol as a method for infantile haemangioma treatment . METHOD: In this study twenty- four patients with infantile haemangioma in different anatomical locations were treated with oral propranolol and the result were assessed in a retrospective analysis of the results patients were kept on 0.25 mg/kg/day for one month , then on 0.5mg/kg/day in 2 divided doses for another one month , in the third month the dose will be increased to 1 mg/kg/day in 2 divided doses , then the propranolol were given in a maintenance do

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Publication Date
Fri Jun 03 2022
Journal Name
Journal Ofxi'an University Of Architecture & Technology
Extent of mathematics teachers' appreciation of the mathematical problem `multiple solutions
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Aims to find out the (Extent of mathematics teachers' appreciation of the mathematical problem `multiple solutions) Research sample consisted of (100) mathematics teachers distributed on the General Directorates of Education in Baghdad (Rusafa 1/2/3) and (Karkh 1/2/ 3) There was two research approach which are: The first - two different answers of students to the same issue where teachers must assess each answer and explain which one the teacher will accept and why? The second - Different solutions of students' to the same issue, including wrong answers , Teachers should correct the answers and give them final grades (0-10). Descriptive and analytical Approch was used in this research methodology And zero hypotheses, which are as f

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Publication Date
Mon Jun 30 2014
Journal Name
Al-kindy College Medical Journal
Efficacy of atorvastatin in treatment of Iraqi obese patients with hypercholesterolemia
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ABSTRACTBackground: dyslipidemia plays a crucial rule in the development of cardiovascular disease, which has become the leading cause of death in most developed countries as well as in developing countries (1). The effects of reducing low density lipoprotein – C (LDL-C) concentrations on the prevention of cardiovascular events and stroke have been well reported in many clinical trials.Objectives: Evidence supports the use of statins for lipid modifications in the primary prevention of coronary artery disease, morbidity and mortality. This study aims to determine the effectiveness of atorvastatin in treating dyslipidemia in Iraqi obese patients.Methods: 200 overweight and obese patients with hypercholesterolemia, according to NCEP ATP

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Publication Date
Tue Jun 14 2022
Journal Name
Al-academy
Representations of puns in the cover designs of Der Spiegel magazine
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 Pun concept the design discourse for the cover of magazines the researcher chose the German magazine Der Spiegel as a model for that, as the research problem was manifested by the following question: What are the representations of puns in the covers of the German magazine (Der Spiegel)? The researcher has identified four chapters for this study as follows: The first chapter is devoted to research procedures, and the theoretical framework, which is like the second chapter, included the literature related to the topic of research according to the two interlocutors. A review of the concept of pun in the field of typographic design and the functions that puns achieve in that field, leading to the third chapter, which included the analysis

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Publication Date
Wed May 17 2023
Journal Name
College Of Islamic Sciences
The origins of the structure of nominative pronouns, a linguistic study
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The Arabic pronouns received a lot of attention from the ancient Arab grammarians, so they explained their origins, the different forms of their structure, and the aspects of the Arabs’ use of them, and explained the aspects and reasons for these uses, with what they had of linguistic insight, which guided them to clarify the truth of these pronouns.
And recently, this research seeks new knowledge of the development of the structure of the nominative pronouns (he), (she), (them), (taa), and (waw) between dialects and towards classical Arabic, by analyzing the structure of these pronouns into their components. Its linguistic formulas are traced from the ancient Arabic texts, and by ancient I mean the texts of the era of linguistic ci

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Publication Date
Mon Mar 07 2022
Journal Name
Journal Of Educational And Psychological Researches
The Purposes of Thinking in the Light of the Holy Qur’an
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This study aims to explain the purposes of thinking in light of the Holy Qur’an. The study adopted the deductive method by analyzing the meanings of the eighteen thinking verses mentioned in the Holy Qur’an That is by referring to the ancient and contemporary book interpretations and inferring the purposes of thinking from the context of those verses. The study concluded that there are seven main purposes, for thinking in the light of the Holy Qur’an, are understanding the universal regulations, contemplating the social codes, inferring, extracting maxims and meanings from the Qur’anic proverbs, analyzing the situation objectively, balancing between interests and evils, and freeing the mind from the authority of the paranormal. T

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Publication Date
Sun Apr 30 2017
Journal Name
Journal Of Engineering
Effect of Construction Joints on the Behavior of Reinforced Concrete Beams
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In this study, the effect of construction joints on the performance of reinforced concrete beams was experimentally investigated. Seven beam specimens, with dimensions of 200×100×1000 mm, were fabricated. The variables were considered including; the location and configuration of the joints. One beam was cast without a joint (Reference specimen), two specimens were fabricated with a one horizontal joint located either at tension, or compression zone. The fourth
beam had two horizontal joints placed at tension, and compression area. The remaining specimens were with one or two inclined joints positioned at the shear span or beam’s mid-span. The specimens were subjected to a monotonic central concentrated loading until the failure. T

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