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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 01 2017
Journal Name
Iraqi Journal Of Agricultural Sciences 47 (1)‏
Effect of irrigation intervals and foliar of salicylic acid on growth and yield of Potato
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Sat Jan 15 2011
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Influence of Source of Oil Added to Diet on Egg Quality Traits of Laying Quail
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This experiment was performed to investigate the influence of different oils in the diets of laying quail on their egg quality characteristics. One hundred and twenty 7-wk old Japanese quails (Coturnix coturnix japonica) were allocated to four groups with three replicates containing 10 quail each (30 quail per each treatment group). They were fed for 13 weeks (including one week of adaptation period) on diets containing 3% oil from different sources, viz. either sunflower (T1), linseed (T2), maize (T3), or fish oil (T4). Inclusion the diet of laying quail with fish oil (T4) and maize oil (T2) resulted in significant increase with respect to egg weight, yolk weight, albumen weight, yolk diameter, yolk height, albumen diameter, albumen height

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Publication Date
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Background: Mouthwashes used widely as ancillary to mechanical oral hygiene methods. Little information provided about the effect of mouthwashes on ions released from orthodontic brackets. Therefore, the present study has been established to evaluate the effect of different mouthwashes on the corrosion resistance and the biocompatibility of two brands of brackets. Materials and Methods: Eighty premolar stainless steel brackets were used (40 brackets from each brand). They were subdivided into four subgroups (n=10) according to immersion media (deionized distilled water, Corsodyl, Listerine and Silca herb mouthwashes). Each bracket was stored in a closely packed glass tube filled with 15ml of the immersion media and incubated for 45 days at

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Sat Dec 31 2022
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Publication Date
Thu Jul 18 2024
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Heresy and Hypocrisy of the Church: A Marxist Analysis of Okezie Nwoka's God of Mercy
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Publication Date
Sat Oct 01 2022
Journal Name
The Egyptian Journal Of Hospital Medicine
Role of Certain Pro-Inflammatory Cytokines in Pathogenicity of Cardiomyopathy in Sample of Iraqi Patients
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Background: Cardiomyopathy (CM) is a cardiac muscle disorder that can lead to heart failure (HF). It has several phenotypes, including dilated, hypertrophic, and restricted. Pro-inflammatory cytokines play a crucial part in the development and advancement of CM. Objective: This study aimed to measure the concentration of certain cytokines [Interleukin- 1β (IL-1β), Interleukin-6 (IL-6), and Tumor Necrosis Factor (TNF-α)] in the serum of Iraqi patients with CM. Materials and Methods: Sixty CM patients and 30 healthy individuals with age ranged from 40 to 70 years old were enrolled in this study through their presence at Iraqi Center for Heart Diseases, Ghazy Al-Hariri Hospital for Surgical Specialties in the Medical City in Baghdad. The st

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Sat Jan 15 2011
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Influence of Source of Oil Added to Diet on Egg Quality Traits of Laying Quail
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The reality of interior design of Sharjah mosques and the possibility of development - selected models
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