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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 May 01 2022
Journal Name
Journal Of Engineering
Comparative Study between the Behavior of the Concrete Thrust Block and the Restraint Joint in a Water Distribution System; Review
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Thrust blocks and restraint joints are the two most popular methods of counteracting the thrust force that generated at pipe fittings (bends, Tee, wye, reducers, dead ends, etc…). Both systems perform the same function, which is to prevent the joints from separating from the pipes. The aim of the study is to review previous studies and scientific theories related to the study and design of thrust blocks and restraint joints to study the behavior of both systems under thrust force and to study the factors and variables that affect the behavior of these systems. The behavior of both systems must be studied because they cannot be abandoned, as each system has conditions whose use is more feasible, scientific, and economic

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Publication Date
Wed Aug 04 2021
Journal Name
Membranes
Model Based Simulation and Genetic Algorithm Based Optimisation of Spiral Wound Membrane RO Process for Improved Dimethylphenol Rejection from Wastewater
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Reverse Osmosis (RO) has already proved its worth as an efficient treatment method in chemical and environmental engineering applications. Various successful RO attempts for the rejection of organic and highly toxic pollutants from wastewater can be found in the literature over the last decade. Dimethylphenol is classified as a high-toxic organic compound found ubiquitously in wastewater. It poses a real threat to humans and the environment even at low concentration. In this paper, a model based framework was developed for the simulation and optimisation of RO process for the removal of dimethylphenol from wastewater. We incorporated our earlier developed and validated process model into the Species Conserving Genetic Algorithm (SCG

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Publication Date
Tue Aug 01 2023
Journal Name
Baghdad Science Journal
First record of peregrine shrimp Metapenaeus stebbingi Nobili, 1904 (Crustacea, Decapoda: Penaeidae) in the Iraqi waters, North-West Arabian Gulf
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One male specimen of the species Metapenaeus stebbingi Nobili, 1904 was first recorded in November 2021 from the Iraqi territorial waters, Northwest of the Arabian Gulf. Therefore, the investigated shrimp species nominally corresponds to the original description of M. stebbing through the main diagnostic features. It must be adopted in the spread and expansion of species, a new record of the area, and a distinctive addition to the species of commercial shrimp within the Iraqi marine waters.

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Publication Date
Mon Oct 01 2018
Journal Name
Journal Of Craniofacial Surgery
Evaluation the Efficacy of Hilotherm Cooling System in Reducing Postoperative Pain and Edema in Maxillofacial Traumatized Patients and Orthognathic Surgeries
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Publication Date
Thu Dec 30 2021
Journal Name
College Of Islamic Sciences
Al-Hajjaj in pre-Islamic poetry hangs Imru 'al-Qays and the Twrfa of Ibn al-Abd as a model
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The topic of (pilgrims) of the old and modern subjects at the same time, as it extends his foot and is associated with the beginning of speech and argument, a modern because it is based on studies and research (and the theory of pilgrims) from (Austin and Cyril) through (Charles Breman) to (Aristotle) ), It is worth mentioning here to mention the role of (Hazem al - Qartagni) in mentioning the value of the pilgrimage of hair and saying the use of persuasion in the hair, is palatable and acceptable. Hence our research applied these views, and we chose the pendants as a model for that matter.

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Publication Date
Fri Dec 19 2014
Journal Name
Al-mustansiriyah
Synthesis, Spectroscopic and Antibacterial Studies of N (2-amino phenyl)-N-((pyridine-2-yl) methyl) Benzene-1, 2-Diamine Complexes
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Publication Date
Tue Jan 01 2013
Journal Name
Advances In Physics Theories And Applications
Tracing and Analysis of Manganese, Nickel, Cadmium ,Copper, zinc , Lead And Aluminum Concentration and PH Values In Iraqi Chewing Gums
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Evaluation of trace elements in Iraqi chewing gums are unavailable, particularly pollution of toxic elements, materials which change the values of PH in the Oral. Atomic Absorption Spectroscopy (AAS) were successfully employed to determine the concentration of 7 trace elements (essentially toxic and nonessential) and the PH, in thirteen different brands of chewing gum generally consumed in Iraq. Combined wet and dry digestion procedures were applied. Two types of heated graphite tubes were used, coated and uncoated tubes treated with tungsten solution. Result showed that Cu, Al and Zn were at very high levels in almost all brands whereas Mn was found to be high in brands A and O only.

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Publication Date
Sun Oct 31 2021
Journal Name
Iraqi Geological Journal
Optimizing Water Injection Performance by Using Sector Modeling of the Mishrif Formation in West Qurna-1 Oil Field, Southern Iraq
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The regular job of a reservoir engineer is to put a development plan to increase hydrocarbon production as possible and within economic and technical considerations. The development strategy for the giant reservoir is a complex and challenging task through the decision-making analysis process. Due to the limited surface water treatment facility, the reservoir management team focuses on minimizing water cut as low as possible by check the flow of formation and injected water movement through the Mishrif reservoir. In this research, a representative sector was used to make the review of water injection configuration, which is considered an efficient tool to make study in a particular area of the entire field when compared with the ful

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Publication Date
Thu Jan 06 2022
Journal Name
Iraqi National Journal Of Nursing Specialties
Effectiveness of Self-Regulation Fluid Program on Patients with Hemodialysis Self-Efficacy for Fluid Adherence in Al-Diwaniyah Teaching Hospital
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Objectives: to evaluate patient knowledge with hemodialysis and to determine the effectiveness of Self-regulation Fluid Program on Patients with hemodialysis self-efficacy for fluid adherence in Al-Diwaniyah Teaching Hospital.

Methodology: A quasi-experimental design (two group design: pre-test and post-test) was used. This study was conducted in Al-Diwaniya Teaching Hospital for the period from (15th of October 2018 to 20th of May 2019) on a non-probability (purposive) sample consisting of (60 patients) treatment in hemodialysis units. A questionnaire was built as a data collection tool and consisted of four parts:

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Publication Date
Thu Oct 01 2020
Journal Name
Biochemical And Cellular Archives
CUT-OFF VALUES OF BLACKCURRANT, LONDON PLANE AND PINE BUDS ON VANCOMYCIN RESISTANT ENTEROCOCCI ISOLATED FROM MASTITIC MILK IN BAGHDAD
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Generation of new clones of multidrug resistant infectious foci of environmental, zoonotic and reverse zoonotic Enterococcus faecalis & faecium strains from cases of mastitis in cows privileged in Baghdad ecosystem reveal unsafe tricks. Medically important plants Blackcurrant, London Plane and Pine Buds are widely used for resolving these public health threats and hazards as powerful antimicrobial preparations. Totally sixty pooled milk samples were collected from apparently healthy (30 units) and infected (30 units) Cows from different regions of Abu-Ghraib during March until July (2019). Integrated units were checked by California mastitis test and a designed scheme was dependent for recovery of pathogenic Enterococci. Gram staining and c

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