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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
Mon Jul 01 2024
Journal Name
Iop Conference Series: Earth And Environmental Science
Effect of Nitrogen and Sulfur Fertilizers on Growth and Yield of Canola
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Abstract<p>For the purpose of determining the impact of three levels of nitrogen fertilizer (0, 60, and 120 kg.ha<sup>-1</sup>) and sulfur fertilizer (0, 40, and 60 kg.ha<sup>-1</sup>) on production and growth indicators (number of leaves, number of branches, chlorophyll pigments, and fresh and dry weights), a field experiment was carried out during the winter season (2021/2022) in the fields of Al-Diwaniyah Province, Ministry of Agriculture, Diwaniyah Agriculture Directorate, Al-Nouriyah Forest Division. Means were compared using the least significant difference test (LSD) at a 0.05 level of probability. In a factorial experiment employing a wholly randomized block design wi</p> ... Show More
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Publication Date
Fri Jul 01 2011
Journal Name
Journal Of Craniofacial Surgery
Management of Retained Foreign Bodies in Missile Injuries of the Maxillofacial Region
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This study evaluates 22 patients with retained foreign bodies in the maxillofacial region that were all caused by penetrating missile injuries. Surgical intervention for the retrieval of the foreign bodies was carried out in 20 patients through the existing wounds and through separate incisions; all patients were followed up for a minimum of 2 months during which all the complications were registered and managed. Preoperative imaging is a prerequisite for the accurate localization of the foreign body and the subsequent successful removal of it. All patients developed complications that were categorized in this study into those that result from the injury itself and those that occur because of the retrieval procedure, the latter category bei

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Publication Date
Sun Dec 31 2023
Journal Name
College Of Islamic Sciences
Features of misleading thought in Quranic discourse and methods of confronting it
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Research summary

The Quranic discourse focused on a lot of vocabularies that carry goals that help man to acquire good, according to a methodology relies on adopting lofty ideas and values. The individual towards society, and the responsibility of society towards the individual. In our present age, the Muslim individual lives in a state of confrontation with deviant ideas, which unfortunately possess the means that make their impact great on society. The study concluded that the Holy Quran contains indicators and determinants of misguided and deviant thought, Which must be avoided because of the seriousness of its effects. Religion, in its general sense, represents a culture that transcends the limits of human ins

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Publication Date
Sat Jan 01 2022
Journal Name
Communications In Mathematical Biology And Neuroscience
The dynamics of the SEIR epidemic model under the influence of delay
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Publication Date
Sat Aug 01 2015
Journal Name
Journal Of Engineering
Influence of Internal Sulfate Attack on Some Properties of High Strength Concrete
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One of the most important problems that faces the concrete industry in Iraq is the deterioration due to internal sulfate attack , since it  reduces the compressive strength and increases the expansion of concrete. Consequently, the concrete structure may be damage .The effects of total and total effective sulfate contents on high strength concrete (HSC) have been studied in the present study.

The research studied the effect of sulfate content in cement , sand and gravel , as well as comparing  the total sulfate content with the total effective SO3 content. Materials used were divided into two groups of SO3 in cement ,three groups of SO3 in sand ,and two groups of SO

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Publication Date
Sun Mar 01 2020
Journal Name
Baghdad Science Journal
Discussing Fuzzy Reliability Estimators of Function of Mixed Probability Distribution By Simulation
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This paper deals  with constructing mixed probability distribution  from exponential with scale parameter (β) and also Gamma distribution with (2,β), and the mixed proportions are (  .first of all, the probability density function (p.d.f) and also cumulative distribution function (c.d.f) and also the reliability function are obtained. The parameters of mixed distribution, ( ,β)  are estimated by three different methods, which are  maximum likelihood, and  Moments method,as well proposed method (Differential Least Square Method)(DLSM).The comparison is done using simulation procedure, and all the results are explained in tables.

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Publication Date
Sat Mar 01 2008
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
External Auditor of responsibility for financial failure And the discontinuity of Company
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Accountancy unit is looked is upon as unit that established for the purpose achieve it goals and programmers for unlimited time. Unless otherwise take place such as liquation whether voluntary or mandatory.  Thus going concern logic is considered to be the logical foundation witch the familiar accounting principles are based upon.  The future of a Company real its financial statues and position and the extent of it ability to face events in future.  Hence the success and continuity its activities depend on the extent of the company activity to generate profits. And its ability to retain appropriate liquidity to serve its debts.

Therefore financial statements of the company consider to be on

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Publication Date
Fri Jun 09 2023
Journal Name
Journal Of Research In Medical And Dental Science
Evaluation of the Anti-inflammatory of Leucaena leucocephala extracts in Experimental Rats.
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A lot of previous studies are concerned with the evaluation of the anti-inflammatory activity of medicinal plants because it considered cheap and are believed to possess minimal side effects. Leucaena leucocephala didn’t evaluate globally for its anti-inflammatory effect yet though some of it’s already separated and identified secondary metabolites were studied and proved to exert many pharmacological activities besides their effect on lowering the pro-inflammatory cytokines like TNF-α and IL-6. So, there was an interest to evaluate the biological effect of Leucaena leucocephala as a novel anti-inflammatory agent was the first motivation to start an in vivo study using a rat population. The N-butanol and ethyl acetate extracts were cho

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Publication Date
Sat Sep 30 2023
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The typical path of compliance control in the verification of tax revenues
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The research aims to contribute to the consolidation of scientific knowledge of compliance control and its role in verifying the proper disposal of funds to manage the wheel of the economy towards achieving targeted development and preserving public money, as well as clarifying the role of tax revenues in strengthening the public treasury and achieving social justice. The analytical descriptive approach was adopted in the process of analyzing The quantitative data collected through personal interviews, and the research reached a set of conclusions, the most important of which is the contribution of compliance control according to its three principles. (Transparency, accountability, and inclusiveness) on the availability

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Publication Date
Sun Dec 06 2009
Journal Name
Baghdad Science Journal
Study of the Porosity of Certain pharmaceutical Tablets using Mercury Intrusion Porosimeter
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Porosity and pore structure are important characteristics of pharmaceutical tablets, since they influence the physical properties, such as mechanical strength, density and disintegration time. This paper is an attempt to investigate the pore structure of four different paracetamol tablets based on mercury porosimetry. The intrusion volumes of mercury were used to calculate the pore diameter, pore volume and pore size distribution. The result obtained indicate that the variation of the pore volume in the tablets followed the sequence:- S.D.I. Iraq? Pharmacare,Dubai-U.A.E.? Bron and Burk(UK) London?Lark Laboratories(India), while the variation of surface area followed the sequence:- S.D.I. Iraq? Lark Laboratories(India)? Pharmacare,Dubai-U.A

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