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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
Wed Nov 27 2024
Journal Name
Frontiers In Education
The impact of using artificial intelligence techniques in improving the quality of educational services/case study at the University of Baghdad
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The utilization of artificial intelligence techniques has garnered significant interest in recent research due to their pivotal role in enhancing the quality of educational offerings. This study investigated the impact of employing artificial intelligence techniques on improving the quality of educational services, as perceived by students enrolled in the College of Pharmacy at the University of Baghdad. The study sample comprised 379 male and female students. A descriptive-analytical approach was used, with a questionnaire as the primary tool for data collection. The findings indicated that the application of artificial intelligence methods was highly effective, and the educational services provided to students were of exceptional

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Fri Feb 01 2019
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Tue Dec 27 2022
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Synthesis, characterization, and application of external gelation of sodium alginate nanoparticles in molecular imprinting for separation and drug delivery of tenoxicam
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Potential Benefits of Ethanol extract of Anredera cordifolia for Antiobesity of High Fat diet-Induced Obesity in White Male Rat Wistar
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Sat Jun 25 2022
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Evaluation of the Possible Protective Effect of Fisetin against Cyclophosphamide-induced Genotoxicity in Bone Marrow and Spleen Cells of Male Rats
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Fisetin is a plant flavonoid found in strawberries and other fruits and vegetables such as apples, persimmons, and onions. It has many pharmacological effects like anti-inflammatory, antioxidant, cardioprotective, neuroprotective, and anti-carcinogenicity which are attributed to its ability to reduce oxidative stress which considers the main reason for different disease conditions. Genotoxicity refers to the genetic material destruction within the cell which can be caused by different chemicals as well as radiation. The present study evaluates the effect of orally-administered fisetin daily for seven constitutive days on genotoxicity induced by cyclophosphamide in rats’ bone marrow and spleen cells. Results showed that fisetin exh

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Thu Apr 01 2021
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Iop Conference Series: Earth And Environmental Science
A Vision to Develop the Effectiveness of the Dissemination of Innovations to Rationalize the Use of Irrigation Water in Iraqi Agriculture
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Abstract<p>Iraqi agriculture faces a major water problem, affecting cultivated areas, agricultural production, farmers’ incomes and food security. However, the results achieved in rationalizing the use of irrigation water are still limited and do not match what they should be in order to meet this serious challenge. The study aimed to provide a vision for the development of the effectiveness of the dissemination of innovations to rationalize the use of irrigation water in Iraqi agriculture. In light of the framework of the dissemination of agricultural innovations, factors related to their effectiveness, and the summary of the Iraqi experience in the field of dissemination of modern irrigation</p> ... Show More
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Tue Jun 23 2020
Journal Name
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The correlation of combined OGG1, CYP1A1 and GSTP1 gene variants and risk of lung cancer of male Iraqi waterpipe tobacco smokers
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Genetic polymorphisms of genes whose products are responsible for activities, such as xenobiotic metabolism, mutagen detoxification and DNA-repair, have been predicted to be associated with the risk of developing lung cancer (LC). The association of LC with tobacco smoking has been extensively investigated, but no studies have focused on the Arab ethnic- ity. Previously, we examined the association between genetic polymorphisms among Phase I and Phase II metabolism genes and the risk of LC. Here, we extend the data by examining the correlation of OGG1 Ser326Cys combined with CYP1A1 (Ile462Val and MspI) and GSTP1 (Ile105Val and Ala103Val) polymorphisms with the risk of LC. Polymerase chain reaction- restriction fragment length polymorphism (

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Publication Date
Tue Jun 30 2015
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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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Publication Date
Wed Jun 07 2023
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The Contribution of Behavioral Disorders to Predicting Bullying Patterns in a Sample of Adolescents with Autism Spectrum Disorder: College of Education and Arts - Northern Border University - Kingdom of Saudi Arabia.
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The present study aims to identify the role of behavioral disorders (anxiety disorder, behavior disorder "behavior", confrontation and challenge disorder, aggressive behavior) in predicting bullying patterns (verbal, physical, electronic, school) in a sample of adolescents with autism spectrum disorder. For this purpose, the researcher developed scales to measure the behavioral disorders and the bullying patterns among adolescents with autism spectrum disorder. The researcher adopted the descriptive survey approach. The study sample consists of (80) adolescents with autism spectrum disorder with ages range from (15-19 years) and (45-53 years old) in association with israr association for people with special needs in the northern borders

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Publication Date
Thu Sep 01 2011
Journal Name
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The use of the methods of the lower squares and the smaller squares weighted in the estimation of the parameters and design of the sample acceptance schemesFor general exponential distribution
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The acceptance sampling plans for generalized exponential distribution, when life time experiment is truncated at a pre-determined time are provided in this article. The two parameters (α, λ), (Scale parameters and Shape parameters) are estimated by LSE, WLSE and the Best Estimator’s for various samples sizes are used to find the ratio of true mean time to a pre-determined, and are used to find the smallest possible sample size required to ensure the producer’s risks, with a pre-fixed probability (1 - P*). The result of estimations and of sampling plans is provided in tables.

Key words: Generalized Exponential Distribution, Acceptance Sampling Plan, and Consumer’s and Producer Risks

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