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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
Tue Jun 30 2015
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
Study the distribution of Fungi and Bacteria in AL- Yusifia River– South of Baghdad City.: Study the distribution of Fungi and Bacteria in AL- Yusifia River– South of Baghdad City.
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Al-Yusifia river was assessed at three sampling stations with study period from Autumn 2010 to the end of Summer 2011. The present investigation was carried out on diversity of fungi and bacteria from Al-Yusifia river, Baghdad city. During the study, a total of 12 fungal genus and 6 bacterial genus were isolated during the year seasons. The dominant fungus at the three stations were Penicillium sp., then Rhizopus and Trichophyton   megninii while the dominant bacteria was Escherichia coli and Klebsiella sp.

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Mon Jan 29 2024
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The cognitive and educational importance of the academic teacher for developing the applied skills of third-stage female students in the subject of teaching methods from their point of view
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A comparative study of the reasons for the reluctance of female physical education teachers in “Baqubah” to participate in refereeing sports competitions according to the variable of years of service
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Mon Feb 16 2026
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The effectiveness of the use of yoga exercises and its impact on the reactions of the two Alvesologih nervous and respiratory systems in the correction of antenna pistol shooting accuracy
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Tue Aug 03 2021
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The impact of tax techniques on the quality of services provided to income taxpayers: An exploratory study in a sample of the branches of the General Tax Authority / Baghdad Governorate
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Perceived organizational support and its relationship to the cognitive competence of the Iraqi National Olympic Committee from the point of view of members of the Olympic sports federations in Iraq
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Thu Jun 30 2022
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THE ROLE OF ELECTRONIC MARKETING IN PROMOTING THE PRODUCTS OF THE NATIONAL INDUSTRY IN IRAQ: THE ROLE OF ELECTRONIC MARKETING IN PROMOTING THE PRODUCTS OF THE NATIONAL INDUSTRY IN IRAQ
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The research aims to clarify the role of electronic marketing and what it can achieve in promoting the products of the national industry in Iraq. Marketing channel depends on modern communication and information technology that industrial and metal companies can use in promoting and selling their products along with traditional marketing outlets. To achieve the objectives of the research, a questionnaire was used, which consists of three axes, the first includes the personal data of the sample (gender, age, educational attainment, place of residence, marital status, income level), while the second axis includes various questions about the products of the national industry. Third axis includes que

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Mon Jan 29 2024
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The cognitive and educational importance of the academic teacher for developing the applied skills of third-stage female students in the subject of teaching methods from their point of view
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Fri Dec 01 2017
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The role of Job description and Perceived organizational support to achieving An Excellent Job performance - An Exploratory study of the views of a sample of department heads at Sulaimaniyah University.
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Mon Apr 01 2019
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The aim of this study was to measure the effectiveness of a proposed program to develop the creative abilities of the students of Tabuk University and its impact on the creative output of the NEOM project. The sample of the study consisted of (50) university students divided into two groups: an experimental group of 25 students who receive the proposed training program, and control group of (25) students.

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