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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 Jan 20 2022
Journal Name
Journal Of Clinical Medicine
Comparison of the Safety and Efficacy of Laser Versus Pneumatic Intracorporeal Lithotripsy for Treatment of Bladder Stones in Children
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This study aimed to compare the safety and efficacy of laser lithotripsy and pneumatic lithotripsy, the two most commonly used transurethral lithotripsy methods for treating bladder stones in children in Iraq. Between January 2013 and December 2016, 64 children with bladder stones were included in this prospective randomized study, after ethical committee approval and written consent from the children’s parents or caregivers were obtained. Patients were assigned randomly by computer software to two groups treated with either pneumatic cystolithotripsy or laser lithotripsy. A 9 Fr. semirigid ureteroscope was used to pass the lithotripter through and fragment the stone. A catheter of 8–12 Fr. was then introduced and kept in place

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Publication Date
Wed Jul 01 2015
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
THE CHEMISTRY OF THE LEAVES OF PLANT Eucalyptus camaldulensis AS ENVIRONMENTAL CONTAMINATION INDICATOR OF SELECTED LOCATIONS AT KIRKUK - IRAQ
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    The environmental contamination by the polycyclic aromatic hydrocarbons (PAHs) and heavy metals (Pb, Cu, Ni, Cr, and Cd) concentrations in the leaves of plant Eucalyptus camaldulensis were determined at the city of Kirkuk in 15 selected locations using GPS. The pickings up of samples were carried out in two periods October 2010 and March 2011. Compared with results of other studies, the concentration levels of determined heavy metals show values within these studies results. The average total concentration of polycyclic aromatic hydrocarbons (PAHs) in the leaves of Plant Eucalyptus camaldulensis indicated 37.1 ppb in October, while in March 165.2 ppb.

 

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Publication Date
Sat Oct 01 2011
Journal Name
Journal Of Baghdad College Of Dentistry
Effect of etchant type and the use of silane on the shear bond strength of composite resin to porcelain
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Background: This study was formulated to compare the effect of 5%hydrofluoric acid in comparison to 37%phosphoric acid with and without the application of silane on bond strength of composite to porcelain. Materials and Methods: Specimen preparation was divided in to two phases, metal-disks fabrication (8mm-diameter and 4mm-thickness) and ceramic veneering. Thirty two specimens were prepared, sandblasted with 50 μm aluminum oxide, and divided into four groups of eight samples. Groups I and III were etched with 37%phosphoric acid while groups II and IV were etched with 5%hydrofluoric acid; and groups I and II were silaneted while groups III and IV were not. Heliobond, and resin composite were applied to each specimen using a plastic transpa

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Publication Date
Tue Jan 01 2008
Journal Name
J Bagh College Of Dentistry
A comparative study of the sealing ability of two different obturation techniques with and without the use of sealers.
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Background: The final stage of endodontic therapy is complete obturation of the root canal system to provide as perfect as possible at the cementodentinal junction of the apical foramen. The purpose of this in vitro study was to evaluate the sealing ability of injection molded thermoplasticized gutta percha and lateral condensation techniques with and without the use of sealers. Materials and Methods: Forty freshly extracted adult human maxillary central incisors with complete formed apices were utilized in this study. The teeth were randomly divided into four groups for evaluation of the apical seal. Group (1) lateral condensation gutta percha technique without sealer, (2) lateral condensation gutta percha technique with sealer, (3) Inject

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Publication Date
Wed May 01 2024
Journal Name
Journal Of Physics: Conference Series
Study of The Effect of Concentration on The Efficiency of The Sensitive N749-TiO<sub>2</sub> Solar Cell
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Abstract<p>In this research, we studied the effect of concentration carriers on the efficiency of the N749-TiO<sub>2</sub> heterogeneous solar cell based on quantum electron transfer theory using a donor-acceptor scenario. The photoelectric properties of the N749-TiO<sub>2</sub> interfaces in dye sensitized solar cells DSSCs are calculated using the J-V curves. For the (CH3)3COH solvent, the N749-TiO<sub>2</sub> heterogeneous solar cell shows that the concentration carrier together with the strength coupling are the main factors affecting the current density, fill factor and efficiency. The current density and current increase as the concentration increases and the </p> ... Show More
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Publication Date
Fri Jan 30 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of the effect of sodium fluoride addition on some mechanical properties of heat cure acrylic denture base materials
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Background: The geriatric patients wearing removable partial dentures are increasing in proportion. At the same time, the root caries prevalence accompanied by gingival recession is increasing. A variety of vehicles can deliver fluoride into the oral cavity, including fluoride mouth-rinse, fluoride dentifrice, topical fluoride, and fluoride-releasing restorative materials, all of which effectively prevent root caries and suppress recurrent caries. This study aimed to evaluate the effect of sodium fluoride addition on some mechanical properties of heat cure acrylic denture base material. Material and method: A total of 90 samples were prepared in this study, then divided into three main groups according to the type of test used (hardness, te

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Takir some study of environmental factors on the weight of some phases of the screwworm fly the ancient world
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The weight of larvae virgins and Alcamlat for males more than the weight of females of the roles themselves that the highest rate of loss in weight of larvae developed to virgins when field conditions were (21.5,22,21.3) mg during June and July and August respectively, recorded the highest degrees of heat and less attributed to moisture

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Publication Date
Sun Jul 01 2012
Journal Name
Journal Of Engineering
Preparation of Design Charts for Estimation of the Length of an Upstream Impervious Blanket in a Homogenous Earth Dam
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Publication Date
Sun Jun 06 2010
Journal Name
Baghdad Science Journal
Effect of Chromium on Growth of green ALGA SCENEDESMUS QUADR ICAUDA (TURP.) DE BERB. With increase of nitrogen concentration
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The study was conducted to identify the toxicity of chromium on scenedesmus quadricauda algae alone and in the presence of nutrient metal (Nitrogen). Different concentrations of chromium (0.5, 1.5 , 2.5, 3.5 , 4.5mg/L) were used and the presence nitrogen is (5 ,10 ,50 ,100mg/L) on cultur media(chu-10) with used for cultivation of the algae in controlled conditions(25oC , light intensity 380 –?E/m2 /s. The results showed increasing in the toxicity of the metal when is alone , excess of concentrations an time of exposure. The growth rate decreased from 0.44 to 0.06 cell/ hour after 12 day of the biging of the experiment and of concentrate 4.5 mg/L of chromium. The intermediate active concentrations of the chromium(EC50) was increase

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Publication Date
Sat Aug 01 2020
Journal Name
Key Engineering Materials
Compressive Strength Performance of Reactive Powder Concrete Using Different Types of Materials as a Partial Replacement of Fine Aggregate
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Reactive Powder Concrete (RPC) can be incorporate as a one of the most important and progressive concrete technology. It is a special type of ultra-high strength concrete (UHSC) that’s exclude the coarse aggregate from its constitutive materials. In this research an experimental study had been carried out to investigate the effect of using three types of materials (porcelain aggregate) and others sustainable materials (glass waste and granular activated carbon) as a partial replacement of fine aggregate. Four percentages had considered (0, 10, 15 and 20) % to achieve better understanding for the influence of these materials upon the compressive strength of RPC. Four curing ages had included in this study, these are; 7, 28, 60 and

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