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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 Jan 16 2022
Journal Name
Applied Sciences
Evaluation of Different Internal Designs of Hydraulic Nozzles under an Accelerated Wear Test
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The use of worn-out agricultural nozzles in pesticide application has a negative effect on the efficiency and cost of the application process. It also has an effect on environmental pollution due to an excessive amount of pesticide being applied when spraying with worn-out nozzles. In this paper, the resistance to wear of three different internal design hydraulic nozzles was ascertained. Changes in the flow rate and spray distribution as a result of this wear were also investigated. The wear test was done inside a closed system, and it was accelerated using an abrasive material to generate 100 h of wear. The tested nozzles were the Turbo TeeJet (TT)-twin chambered, Turbo Twinjet (TTj60)-dual outlet, and Drift Guard (DG)-pre-orifice.

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Publication Date
Mon Jul 01 2019
Journal Name
Iop Conference Series: Materials Science And Engineering
The use of Mixed Bacterial Culture to improve the Biodegradation of Diesel Pollution
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This study was conducted to evaluate the hydrocarbon biodegradation abilities of Enterobacter cloacae, Staphylococcus aureus, Sphingomonas paucimobilis, and Pentoae species which were isolated from different diesel-contaminated soil samples. The isolates were identified by the Vitek 2 system. Fourier-transform spectroscopy (FT-IR) tested the potential of these isolates to biodegrade the diesel according to the peak areas, a significant decrease in the area of the peaks at 2856-2928 cm−1 corresponds to aliphatic hydrocarbons. The appearance of small peaks at 900-1032 cm−1 refers to substituted benzene derivative compounds. An appearance of some new peaks at 3010- 3030 cm−1 which indicate the presence of alcohol (-OH) and ketones (RC=O)

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Publication Date
Tue Nov 03 2020
Journal Name
Iium Medical Journal Malaysia
Role of the Immunohistochemical Marker (Ki67) in Diagnosis and Classification of Hydatidiform Mole
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Introduction: Since the hallmark of gestational trophoblastic disease is trophoblastic proliferation, Ki67 is regarded as the best marker in studying hydatidiform mole.This study was conducted to evaluate the role of this proliferative marker in distinguishing among hydropic abortion, partial and complete hydatidiform mole. Materials and methods: This is a cross sectional study involving the application of Ki67 on a total of 90 histological samples of curetting materials from molar (partial and complete mole) and non molar hydropic abortion belong to Iraqi females, so three study groups were created. Immunohistochemical expression in villous cytotrophoblasts, syncytiotrophoblasts and stromal cells were recorded separately by three i

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Publication Date
Thu Feb 24 2022
Journal Name
Journal Of Educational And Psychological Researches
The Psychometric Properties of the Arabic Version of Nomophobia Scale among Omani Youth
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The current research aimed to investigate the psychometric characteristics of the Arabic version of the Nomophobia scale for the Omani youth. The scale was administered to a random sample of students from public and private universities and colleges in Oman. The research sample consisted of 2507 students, of whom 868 males and 1639 females. The validity of the measure was first checked by presenting the scale to a group of experts in this field. Then the exploratory and confirmatory factor analysis was carried out. The exploratory factor analysis revealed the existence of three main factors: the fear of connectivity loss, the fear of communication loss with others, and the fear of network outages. These factors accounted for 65.6% of the

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Publication Date
Thu May 05 2022
Journal Name
Al-kindy College Medical Journal
Prevalence of Cytomegalovirus Infection among Suspected Infants in Baghdad: Prevalence of CMV Infection
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Background: Cytomegalovirus (CMV) virus is a recognized important cause of congenital CMV infection which carries a significant risk for symptomatic disease and developmental defects in newborns. Its prevalence varies from place to other and time to time. This study is conducted to estimate its prevalence in Baghdad among infants suspected of having a congenital infection and to study the associated findings.   

 Subjects and Methods: The study was carried out in Al-Alwyia pediatrics teaching hospital. Data were collected, and blood samples were taken for infants suspected to have intrauterine infections over a period of one year, from 1 October 2019 to 1 October 2020.  Immunoglobulin M (IgM) tests for CMV w

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Publication Date
Thu Nov 08 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Effect of using two packing Technic on Hardness of two dental acrylic resin
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Objective: the aim of this study is to invest age and determine the effect of using (2) packing
technique (conventional and new tension technique) on hardness of (2) types of heat cure acrylic
resin which are (Ivoclar and Qual dental type).
Methodology : this study was intended the using of two types of heat cure acrylic (IVoclar and
Qual dental type) which are used in construction of complete denture which packed in two different
packing technique (conventional and new tension technique) and accomplished by using a total of
(40) specimens in diameter of ( 2mm thickness, 2 cm length and 1 cm width) . This specimens were
sectioned and subdivide into (4) group each (10) specimens for one group , then signed as (A, Al B

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Publication Date
Wed Jun 27 2018
Journal Name
University Of Leicester
The Convective Instability of BEK Family of Non-Newtonian Rotating Boundary-Layer Flows
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The BEK family of flows have many important practical applications such as centrifugal pumps, steam turbines, turbo-machinery and rotor-stator devices. The Bödewadt, Ekman and von Kármán flows are particular cases within this family. The convective instability of the BEK family of rotating boundary-layer flows has been considered for generalised Newtonian fluids, power-law and Carreau fluids. A linear stability analysis is conducted using a Chebyshev collocation method in order to investigate the effect of shear-thinning and shear-thickening fluids for generalised Newtonian fluids on the convective Type I (inviscid crossflow) and Type II (viscous streamline curvature) modes of instability. The results reveal that shear-thinning power-law

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Publication Date
Sat Jun 30 2012
Journal Name
Al-kindy College Medical Journal
Diagnostic Accuracy of Different Radiological Investigations in the Diagnosis of Perforated Duodenal Ulcer
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Background; Perforated duodenal ulcer (PDU) is a common surgical emergency that is associated with high mortality and morbidity. Early diagnosis and prompt surgical treatment is required to prevent grave complications.
Objective; The study was designed to evaluate the diagnostic accuracy of different radiological investigations in the diagnosis of perforated duodenal ulcer.
Methods; A prospective study of 185 pts with PDU at al kindy teaching hospital, Baghdad, Iraq from June 2008- august 2010. patients were examined clinically and investigated by blood test, chest x ray, plain X ray of the abdomen. Ultrasonography (U/S) and CT scanning done for those patients with negative X- ray finding. Resuscitation by intravenous fluid and ant

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Publication Date
Sat Jun 30 2012
Journal Name
Al-kindy College Medical Journal
Correlation of Concentrations of Certain Trace Elements in Normal and Diseased Human Tissues
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Background Over the past decade there has been a growing awareness of, and interest in, the trace element concentration differences between normal and diseased tissues. Significant changes in tissue concentrations of Zinc (Zn) and Copper (Cu) have been previously reported in inflammation and cancer of certain human tissues.
Aim:(1)To correlate between Zn and Cu concentrations and the histological picture of normal and certain inflamed human tissues, namely the gall bladder (GB) the vermiform appendix (VA), visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). (2) to detect whether there is a difference in the above-mentioned parameters between VAT and SAT. (3) to obtain recordings for trace element levels in human tissu

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Publication Date
Wed Jan 01 2014
Journal Name
Journal Of The College Of Languages (jcl)
The Allegorical Use of the Rituals of Hunting in Galway Kinnell's "The Bear"
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Galway Kinnell (1927-) is considered as one of the most important contemporary American poets who brought about a drastic change in the American poetry of the nineteen sixties. Kinnell's poetry is characterized by being simple in style and deep in content. Poetry for him is a means through which he perceives the inner levels of consciousness in an attempt to comprehend the depths of the American self. Therefore, he writes narrative poems in which the emphasis is not on the rhetorical effects, but on the inner transformations through which the poet goes.

"The Bear" (1968) is typical of Kinnell's introspective poetry. It takes the form of a journey in which the rituals of hunting are used allegorically to embody the state of the sp

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