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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 05 2011
Journal Name
Baghdad Science Journal
The study of antibacterial activity of some plant extracts against causes of pneumonia
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Eighty five samples were taken from patients suffering from pneumonia. Seventy-eight isolates were diagnosed as following: Staphylococcus aureus (23), klebsiella pneumoniae (29), Streptococcus pneumoniae (15), Serratia sp. (4), Haemophilus influenzae (4) and Pseudomonas aeruginosa (3). The clinical isolates were tested for antibiotics sensitivity. They appeared highly resistance to penicillin G and Ampicillin at percentage 89.7 and 84.6% respectly while the results showed highly sensitivity to streptomycin at percentege of (12.8%). To study the antibacterial activity of Alium sativum, Eucalyptus microtheca leaves and Cydonia oblonga seeds extracts, five multi resistant strains were used by using agar well diffusion and disk methods at c

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Mon Apr 10 2023
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Journal Of Oral And Dental Research
Prevalence of Temporomandibular Joint Disorder among Dental Students of the University of Baghdad
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Tue Jan 01 2013
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The study of food preference of Callosobruchus maculatus to five types of fabaceae
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Wed May 10 2023
Journal Name
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EFFECT OF CHANGE IN THE COEFFICIENT OF PERMEABILITY ON CONSOLIDATION CHARACTERISTICS OF CLAYS
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The settlement rate and pore water pressure dissipation rate are mainly controlled by the permeability of soil. Both laboratory and field tests show that the permeability is varied during the loading and consolidation process. It is known that consolidation process is accompanied by decrease in void ratio which leads to decrease in the coefficient of permeability. The importance of the decrease of the coefficient of permeability on the time rate of settlement and pore water pressure needs to be investigated.
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Publication Date
Sun Apr 02 2017
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Journal Of Educational And Psychological Researches
Standraidization of Post traumatic Stress Disorder Scale on Students of University of Baghdad
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There are a lot of measures for Post Traumatic Stress Disorder (PTSD), but what distinguishes it from other measures is the number of short paragraphs and concise depending on the classification of American Psychiatric Association (APA), which can be applied by the researchers on a large number, Because the Iraqi society suffered from psychological trauma due to wars, conflicts and occupation and the resulting psychological disorders of the members of Iraqi society, especially post-traumatic stress disorder, as mentioned by many studies and researches.

Therefore, the aim of this study was to standardize the PTSD scale for students at Baghdad University. For the Psychologist Fua . E. which was applied in many foreign studies. 

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Publication Date
Sun Mar 01 2009
Journal Name
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Effect of Gamma Rays on Some Stages of Development of Rhyzopertha dominica (Fab.)
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Publication Date
Sat Dec 01 2012
Journal Name
Journal Of Economics And Administrative Sciences
Philosophy of resolving the forces of contradiction in the theory of the organization
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The current research aims to provide a philosophical and knowledge framework  to explain the issue of organizations dealing with Paradox phenomena by focusing on five main aspects. The first deals with the concept of paradox, and the second aspect deals with the types of forces paradox. While the third aspect regards subject of the philosophy of paradox in organization theory and the fourth side deals with methods of   solving the paradox. Finally, the last side is exposed to the subject of the paradoxes of the three provided by the study (L

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Wed Jan 30 2013
Journal Name
Al-kindy College Medical Journal
The Role of Glucosamine Chondrotin Sulfate in the Treatment of Osteoarthritis of Knee
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population .its etiology relates to a strong ,but
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with mechanical and metabolic factors that cause
molecular alterations the end results of which
affect the whole joint .Glucosamine and
chondrotin sulfate alone or in combination may be
of benefit to a subgroup of individuals who have
knee pain due to OA.
Glucosamine has been shown to alter cartiage turn
over in patients with OA undergoing physical
training
Aim of the study: To find the validity of
glucosamine chondrotin sulfate in treatment of
grade 1 and 2 OA.
Methods: the sample of 280 patients

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Publication Date
Mon Jan 01 2018
Journal Name
Iraqi Journal Of Embryos & Infertility Researches
Analysis of Amino Acids of the Brain in Embryo and Adult of Quail.
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Amino acids have the role in the process of proteins synthesis. They are an essential source of nitrogen atoms that have a role in the pathways of synthetic reaction pathways. The carbon skeletons of the amino acids are the source of energy in addition to their role as precursors in the paths of interactions. The amino acids analysis for the brain of the quail bird in different stage of development (10-16 days of incubation) in addition to the hatching stage (17th day) and the adult. Materials and Methods: Amino Acids Analysis The amino acids were separated from the embryos and adult brains of the quail bird Coturnix coturnix and were diagnosed based on standard amino acids, using high performance liquid chromatographic device (H.P.L.C.). R

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Mon Jan 01 2024
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Effectiveness of Frenulum Subcutaneous Injection of Botox in the Treatment of Premature Ejaculation
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