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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 May 22 2022
Journal Name
International Journal Of Early Childhood Special Education (int-jecs)
The image of Al-Shuhada'a Establishment among the families of martyrs, victims of terrorism, war operations and military mistakes
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This research (The families of martyrs, victims of terrorism, war operations and military mistakes opinion about Al- Shuhada`a Establishment ) came to know and diagnose the mental image the martyrs victims of terrorism carries about the performance of Al- Shuhada`a Establishment and the services it provides to them, and to monitor the contents of that image that they had regarding their privileges and rights that Al- Shuhada`a Establishment supposed to give it to them, according to their law. The research problem was represented by the main question: (What is the image of Al- Shuhada`a Establishment among the families of martyrs, victims of terrorism, war operations and military mistakes), and this research was classified within the d

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Publication Date
Sun Jun 01 2014
Journal Name
Baghdad Science Journal
Effect of Some Medicinal Plants on the Activity of Some Immunological Factors in Saliva and Serum of Type –?? Diabetics
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The study involved 45 male and 45 females of diabetic patients type- ?? aged from 40-69years , and with the same numbers of males and females for control , all the patients and controls were without any periodontal diseases and without any systemic disease. Diabetic patients were divided in to three groups according to the degree of periodontitis , and the inflamed gingiva of all groups of diabetic patients were treated with the dried fruits powder (crude) of medicinal plants Quercus robur , Thuja occidenalis , Terminalia chebula, Anethum graveolens , respectively and mixture. Some immunological and antimicrobial factors (IgA, Lactoferrin , Lysozyme ) , were detected in serum and saliva of diabetic patients and the control

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Publication Date
Sun Aug 13 2017
Journal Name
Iraqi Journal Of Agricultural Sciences
EFFECT OF SUPPLEMENTING DIFFERENT LEVELS OF CONJUGATED LINOLEIC ACID (CLA) TO THE DIET ON PRODUCTIVE PERFORMANCE OF BROILER CHICKEN
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This study was carried out at Poultry Research Station, State Board of Agricultural Research, Ministry of Agriculture for the period from 27 September 2014 to 9 November 2014 to evaluate the Supplementation of different levels of Conjugated Linoleic Acid (CLA) on productive performance of broiler. Four hundred eighty chicks (Ross-308),one day old were randomly distributed to four dietary treatments for 42 days of age with 3 replicates/vtreatment (40 bird/replicate). Experimental treatments were as follow; T1 (Control diet) without supplement, while the treatment T2,T3 and T4  were Supplemented with 1, 1.5, 2 g CLA /kg diet  respectively. The results showed significant (P ≤ 0.05) increased in mean of body weight, weight gain, ave

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Publication Date
Sat Jul 01 2023
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The impact of the practice of professional doubt on the quality of the auditor's performance in Iraq: بحث استطلاعي
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              Due to the increasing interest in the quality of auditing by writers, researchers and regulators of the auditing profession. The matter necessitated a statement of the extent to which the auditor practices professional skepticism, because of its significant impact in discovering errors and material misrepresentations contained in the financial statements in order to give the financial community confidence in them and the success of the audit process. The research aims to clarify the concept and importance of the practice of professional skepticism and its effect on the quality of the auditor's performance in Iraq. To achieve the research objectives, the two re

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Publication Date
Sun Oct 01 2023
Journal Name
Baghdad Science Journal
The Influence of Ablation Speed on the Synthesis of Carbon Nanostructures Via Pulsed Laser Ablation of Asphalt in Ethanol
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Pulsed liquid laser ablation is considered a green method for the synthesis of nanostructures because there are no byproducts formed after the ablation. In this paper, a fiber laser of wavelength 1.064 µm, peak power of 1 mJ, pulse duration of 120 ns, and repetition rate of 20 kHz, was used to produce carbon nanostructures including carbon nanospheres and carbon nanorods from the ablation of asphalt in ethanol at ablation speeds of (100, 75, 50, 10 mm/s).  The morphology, composition and optical properties of the synthesized samples were studied experimentally using FESEM, HRTEM, EDS, and UV-vis spectrophotometer. Results showed that the band gap energy decreased with decreasing the ablation speed (increasing the ablation time), the mi

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Publication Date
Tue Dec 13 2011
Journal Name
Iraqi Journal Of Laser
The Effect of 532nm Nd: YAG Pulsed Laser on the Activity of Superoxide dismutase and Alcoholdehydrogenase of Saccharomyces Cerevisiae
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In this study, the effect of Nd: YAG laser on the activity of superoxide dismutase (SOD) and alcoholdehydrogenase (ADH) was investigated. The Saccharomyces cells were irradiated using 532nm Q-Switched Nd: YAG laser with (1Hz) frequency. Different fluences 11.3, 22.6 and 33.9mJ/cm2 and different number of pulses 15, 30 and 60 pulse were used. The irradiated cells were incubated in a liquid nutritive medium for 24 hours. After incubation, the cells were harvested and disrupted to extract the intracellular enzymes and their activities were assessed. In comparison with the control, the irradiated cells showed a significant increase in the activity and the specific activity of SOD at energy densities of 11.3 and 22.6mJ/cm2 at 30 and 60 pulses

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Publication Date
Tue Sep 15 2020
Journal Name
Al-academy
Formal Function of Guiding Sign in the design of Interior Spaces of Airports: أسـامـة غانـم نـوري -أحمـد ناجــي علــي
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  The research addressed the formal functions resulting from the use of various guiding signs in the design of the interior spaces of airports in various pragmatic, expressive and psychological aspects. The aim is to identify the functions the guiding signs perform in facilitating and organizing the travelers' movement and satisfying the needs of the visitors and users of the unfamiliar places which they intend to visit, the nature of the services offered by these signs as one of the important parts within their general design. The research also identified the concept and types of signs as a means of visual communication and how to employ them in the design of the airports public spaces, and what are the criteria of their use and fu

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Publication Date
Tue Mar 15 2022
Journal Name
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The semiotics of the visual image of women in the discourse of empowerment, Saudi Arabia Kingdom as a model
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We studied, in this paper, the semiotics of the visual image of women in the discourse of empowerment, through three models of advertising images expressing the particularities of the Saudi Arabian environment.

We aim to know how the mark operates and how it is interpreted, as a semantic process in which the meaning ranges from description to interpretation, and we studied two hypotheses:

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-The significance is not found in the visual sign or in the textual sign of the advertising image, but in the creative event that opens up to the social, cultural, and psychological context, and creates a field of dia

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Publication Date
Thu Jan 11 2024
Journal Name
Tropical Journal Of Pharmaceutical Research
Application of Taguchi orthogonal array in optimization of the synthesis and crystallinity of metal organic framework 5 (MOF 5)
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Purpose: To use the L25 Taguchi orthogonal array for optimizing the three main solvothermal parameters that affect the synthesis of metal-organic frameworks-5 (MOF-5). Methods: The L25 Taguchi methodology was used to study various parameters that affect the degree of crystallinity (DOC) of MOF-5. The parameters comprised temperature of synthesis, duration of synthesis, and ratio of the solvent, N,N-dimethyl formamide (DMF) to reactants. For each parameter, the volume of DMF was varied while keeping the weight of reactants constant. The weights of 1,4-benzodicarboxylate (BDC) and Zn(NO3)2.6H2O used were 0.390 g and 2.166 g, respectively. For each parameter investigated, five different levels were used. The MOF-5 samples were synthesi

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Publication Date
Sun Jul 28 2019
Journal Name
Open Access Macedonian Journal Of Medical Sciences
Value of Combination of Standard Axial and Thin-Section Coronal Diffusion-weighted Imaging in Diagnosis of Acute Brainstem Infarction
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AIM: To determine the value of the combination of thin-section 3 mm ‎coronal and standard ‎axial DWI and their impact in facilitating the diagnosis of ‎‎acute brainstem infarction. METHODS: A cross-sectional study conducted from the 1st of April 2017 to the end of February 2018 on 100 consecutive patients (66% were male, and 34% were female) with isolated acute ischemic infarction in the ‎brainstem. The abnormal MRI findings concerning the ischemic lesions were interpreted on standard axial 5 mm and thin-section coronal 3mm DWI. RESULTS: The mean age of the studied group was 69.2 ± 4.3 for male and 72.3 ± 2.5 years. The standard axial DWI can diagnose 20%, 6.7% and 6.7% of the infarctions in midbrain, pons an

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