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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 Jun 27 2021
Journal Name
Iraqi National Journal Of Nursing Specialties
Level of Depression and Anxiety among School Age Children with Acute Lymphoblastic Leukemia under Chemotherapy Treatment at Pediatric Teaching Hospitals in Baghdad City
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Objective(s): To assess the level of depression and anxiety among school age children with acute lymphoblastic leukemia under chemotherapy treatment and to find out the relationship between the level of depression and anxiety among the affected children and their demographic characteristics.
Methodology: A cross-sectional study was conducted on school age children both gender having acute lymphoblastic leukemia under chemotherapy treated and their age between 6 years to 12 years. The study started from the period of September, 19th 2020 to March,1st 2021. Non-probability (Purposive) sample of (114) children with acute lymphoblastic leukemia under chemotherapy was selected in attending hospital wards, outpatient and counseling clinics

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Publication Date
Wed Aug 28 2019
Journal Name
International Journal Of Drug Delivery Technology
Synthesis, Characterization and Screening their Antibactrial Activity of some New Oxazepine and Diazepine Compounds Containing 1,3,4-Oxadiazole Ring Derived from L-Ascorbic Acid
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The search involve the synthesis of some new 1,3-oxazepine and 1,3-diazepine derivatives were synthesized from Schiff base. The Schiff base (VIII) prepared from reaction of aldehyde (IV) derived from L-ascorbic acid with aromatic amine ([2-(4- nitrophenyl)-5-(4-aminophenyl)-1,3,4-oxadiazole] (VII). Oxazepine compounds (IX-XI) were synthesized from the cyclic condensation of Schiff base (VIII) with (maleic, phthalic and 3-nitrophthalic) anhydride, compounds (IX-XI) that were reacted with p-methoxyaniline to give diazepine derivatives (XII-XIV). The structures of the new synthesized compounds have been confirmed by physical properties and spectroscopy measurements such as FTIR, and some of them by 1 H-NMR, 13 CNMR, Mass, and evaluated

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Publication Date
Mon Jun 24 2024
Journal Name
International Tinnitus Journal
Distribution of HPV Genotypes 16 and 18 among Resected Tonsillar Tissues from Pediatric Patients Operated for Non- Oncologic Nasopharyngeal and Palatine Tonsillar Hypertrophies
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Background: Recent advancements in molecular techniques have identified over 450 genotypes of Human Papillomavirus (HPV), classified into low- and high-oncogenic risk categories. The rise in high-oncogenic risk HPV genotypes has been linked to various cancers, including those affecting the oral, oropharyngeal, and nasopharyngeal regions in both pediatric and adult populations. Methods: In this study, a cohort of 102 tonsillar tissue samples was included. This comprised 40 specimens from pediatric patients aged 4 to 9 years with nasopharyngeal adenoid hypertrophies, and 42 specimens from pediatric patients aged 5 to 12 years with palatine tonsillar hypertrophies. Among the 82 tonsillar tissue samples analyzed, 38 were from pediatric patients

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Publication Date
Sat Jun 01 2019
Journal Name
Telematics And Informatics
Corrigendum to “Modelling the utilization of cloud health information systems in the Iraqi public healthcare sector” [Telematics and Informatics, 36 (2019) 132–146]
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Publication Date
Wed Nov 01 2017
Journal Name
Iraqi Journal Of Community Medicine
Zinc Sulphate 5% Mouthwash is an Effective Therapeutic and Prophylactic Agent in Treatment of Recurrent Aphthous Ulcer (Single blind placebo controlled therapeutic study).
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Publication Date
Wed Jul 08 2009
Journal Name
Ibn Al-haitham Journal For Pure And Applied Science
Complexeation Behavior of CoII, NiII, CuII, ZnII, and CdII Ions Toward Schiff Base Derived From 2, 4 -Dihydroxy Benzaldehyde and O-Phenylene Diamine
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bstract The aim of this work covers the synthesis and characterization of the new tertra dentate ligand (H4L) containing (N and O) as donor set atoms kind (N2O2) where: H4L=Bis-1,2 (2,4- dihydroxybenzylediene phylinediamine . The preparation of ligand contains reaction 2, 4 - Dihydroxy benzaldehyde and o-phenylene diamine . Schiff base was reacted with some metal ions in the presence of methanol to give the complexes in the general formula [M (H2L)] where: MII = Co, Ni, Cu, Zn, Cd. All compounds were characterized by spectroscopic methods I.R , U.V.-Vis, metal content and molar conductivity measurements, showed that the complexes are non-electrolyte. The proposed geometry for all of the proposed complexes was a tetrahedral while Ni complex

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Publication Date
Tue Jan 01 2019
Journal Name
الأستاذ
Teaching-learning design according to constructivist theory models and its impact on the achievement of chemistry among second-year intermediate school female students
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Publication Date
Thu Mar 31 2022
Journal Name
American Journal Of Economics And Business Management
Measuring and Analyzing the Factors Affecting the Behavior of Government Spending in Iraq Using the Co-Integration Test for the Period 2000-2020
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Government spending is the tool that the state uses to achieve its various goals. The research aims to identify the most important determinants of government spending in Iraq and to indicate the type and nature of the relationship between government spending and its determinants, which will contribute to understanding the movement of government spending. The results of the co-integration test using the border test methodology showed that the variables of population growth and oil prices have a long-term effect on government spending while inflation is not significant in the long run, and that 47% of the equilibrium imbalance (short-term imbalance) in government spending in the previous period (t-) can be corrected in the current period (t)

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Publication Date
Tue Sep 27 2022
Journal Name
Al–bahith Al–a'alami
CREATIVITY IN THE TELEVISION ADVERTISING MESSAGE AND ITS EFFECTIVENESS IN ATTRACTING THE ATTENTION OF THE RECIPIENT: (A research drawn from a Degree thesis)
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Declaration has become today has an important and active and influential role in the recipient public life، and are concentrated advertising on the creativity component manufacture to attract his attention toward what to be announced from a variety products، and is dominated by television commercials tempo and imagination، and display them a variety of ways catches the attention and an impressive simulates the their senses of hearing and sight، to influence in the receiver and the public paid for purchase.

Through it crystallization the subject of our research on the importance of creativity in television advertising and effective for attracting the attention of the publi

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Publication Date
Fri Jan 01 2021
Journal Name
Revista Iberoamericana De PsicologÍa Del Ejercicio Y El Deporte
SPECIAL EXERCISES IN THE HIERARCHICAL OPPOSING TRAINING METHOD AND ITS EFFECT ON DEVELOPING PHYSICAL ABILITIES AND ACCURACY OF SOCCER SCORING FOR ADVANCED PLAYERS
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