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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
Thu Sep 01 2011
Journal Name
Journal Of Economics And Administrative Sciences
The impact of market orientation and the commitment of employees to performance
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أستهدفت الدراسة اختبار أثر التوجه السوقي والتزام العاملين على أداء المنظمة المسوقة لخدمات النقل الجوي. حيث تم اختيار شركة الخطوط الجوية الملكية الأردنية كمجال تطبيقي.وقد اعتمدت الدراسة في قياس المتغيرات على مقاييس مختبرة وقد تأكد صحتها وثباتها لقياس المتغيرات في البيئة الحالية.  وقد بينت نتائج التحليل الإحصائي الذي استخدمت فيه أساليب إحصائية مختلفة بالاستعانة ببرنامج SPSS))

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Fri Jun 16 2023
Journal Name
Acta Scientiarum Polonorum Administratio Locorum
An analysis of Baghdad’s masterplans based on the development of green areas
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The Concept of the Constitution and the most Important of Human Rights
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Mon Apr 01 2019
Journal Name
Journal Of Engineering
The Influence of the Preparation and Stability of Nanofluids for Heat Transfer
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Most appropriate conditions of the binding of LH in Benign and Malignant
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Publication Date
Thu Jul 09 2020
Journal Name
Agrosystems, Geosciences & Environment
Yield and quality of three potato cultivars under series of nitrogen rates
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Sat Jun 01 2019
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Thu Apr 30 2020
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Econometrics of the impact of financial inclusion on banking stability in Iraq
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        Financial inclusion refers to the access of financial services at low cost and high-quality from the formal financial sector to all segments of society, especially marginalized groups, and then use and benefit from them. Financial inclusion is also associated with banking stability, as well as with financial integrity and financial protection for the consumer, therefore, it achieves a number of objectives, the most important of which is to support and enhance banking stability. This is what made it attract the attention of many countries and central banks recently.

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The Influence of Nanomaterials on the Permanent Deformation of Hot Mix Asphalt
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Improving the permanent deformation resistance of asphalt pavements is a vital challenge. Nanomaterials have emerged as promising additives due to their ability to enhance the binder stiffness and elasticity. This study evaluated the influence of five nanomaterials, namely Nano-Silica (NS), Nano-Alumina (NA), Nano-Zinc (NZ), Nano-Titanium (NT), and Carbon Nanotubes (CNTs) incorporated into a base asphalt binder at varying dosages, with up to 10% for NS, NA, and NT, and up to 5% for NZ and CNT. Fifteen modified binders were assessed using the Multiple Stress Creep Recovery (MSCR) test to obtain non-recoverable creep compliance (Jnr), while the corresponding hot mix asphalt samples underwent repeated load testing and rut depth predict

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