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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
Mon Jan 01 2018
Journal Name
World Journal Of Dentistry
Factors affecting the Duration of Surgical Extraction of Impacted Mandibular Third Molars
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Aim The aim of this study is to evaluate the effect of demographic, clinical, and radiographic factors on the duration of surgical extraction of impacted lower third molars. Materials and methods This retrospective study included patients who underwent surgical removal of impacted lower third molars, and the investigated factors were demographic data including age and gender, radiographic data including the impacted tooth angulation and depth of impaction and ramus relation, and clinical data including the state of eruption of the impacted teeth. These factors were evaluated for association with the duration of surgery. Descriptive statistical analysis included percentages and mean ± standard deviation (SD). Student's t-test was used to co

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Publication Date
Sun Sep 04 2016
Journal Name
Baghdad Science Journal
Bioadsorption of Heavy Metals From Industrial Wastewater Using Some Species of Bacteria
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Three isolated bacteria were examined to remove heavy metals from the industrial wastewater of the Diala State Company of Electrical Industries, Diyala-Iraq. The isolated bacteria were identified as Pseudomonas aeruginosa, Escherichia coli and Sulfate Reducing Bacteria (SRB). The three isolates were used as an adsorption factor for different concentrations of Lead and Copper (100, 150, and 200 ppm.), in order to examine the adsorption efficiency of these isolates. In addition, the effect of three factors on heavy metals adsorption were examined; temperature (25, 30, and 37 ?C), pH (3 and 4.5) and contact time (2 and 24 hrs). The results showed that the highest level of lead adsorption was obtained at 37 ?C by E. coli, P, aerugenosa and

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Publication Date
Fri Dec 20 2024
Journal Name
Bulletin Of The Iraq Natural History Museum
MORPHOLOGICAL CHARACTERIZATION OF BLOWFLY MAGGOTS (DIPTERA, CALLIPHORIDAE) FROM THE MIDDLE OF IRAQ
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This study aimed to conduct a comparative analysis of seven calliphorid species of third- instar larvae that were collected from central Iraq. The purpose was to morphologically characterize these species and develop an identification key to differentiate them from closely related species. Scanning Electron Microscope (SEM) graphical images and high-resolution traditional optical microscopes were used to analyze the morphological characteristics of the species Calliphora vomitoria (Linnaeus, 1758), C. vicina Robineau-Desvoidy, 1830, Chrysomya albiceps (Widemann, 1819), Ch. rufifacies (Macquart, 1844), Ch. megacephala (Fabricius, 1794), Lucilia cuprina (Wiedemann, 1830), and L. sericata (Meigen, 1826). An identification key was const

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Publication Date
Tue Jun 01 2021
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Time series analysis of the number of covid-19 deaths in Iraq
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Publication Date
Wed Dec 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Comparison of Immunohistochemical Expression of DNMT3B among Oral, Laryngeal and Skin SCC
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Background: Recently epigenetic alterations have received increased attention because of theirimportant role in the process of tumerigenesis. It has been found that more than half of genetic changes were epigenetic. Epigenetic alterations are catalyzed by DNMTs enzymes. Increased knowledge about this molecular event may achieve progress in the war against cancer. The aim of this study was to evaluate and compare the expression of DNMT3B among oral, laryngeal and skin SCC. Materials and Methods: This study was performed on (120) formalin-fixed, paraffin-embedded blocks, histopathologically diagnosed as oral, laryngeal and skin SCC). Immunohistochemical staining of DNMT3B antibody was performed on each case of this study. Results: The immunoh

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Publication Date
Tue Dec 06 2022
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation of Nurses' Attitudes towards Patients’ End of life in Diyala Governorate
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Abstract:

Objectives: To assess nurses' attitude toward end of life phase. To find out  relationships between nurses attitude and socio demographic data (age, gender, level of education, years of experience).

Methodology: A descriptive cross-sectional study design is carried out to assess the attitude on nurses concerning patient at the end of life phase at critical care units, from the period of (1nd November 2021) to (1th February 2022). A probability sample random sampling technique used. Then, the number of participants in Baquba Teaching Hospital and general al khalis hospital were determined by using rando

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Publication Date
Tue Oct 01 2019
Journal Name
October-2019
Histological assessment of the efficiency of rabbit serum in healing skin wounds
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Aim: This study aimed to investigate the impact of rabbit serum on skin wound healing with the help of histological examination. Materials and Methods: A total of ten indigenous rabbits were used in this study. The animals were divided into two groups: control and serum- treated. The histological assessment was done with a paraffin embedding technique and the histological sections were stained with H&E stain. Results: Severe infiltration of polymorphonuclear leukocytes with severe fibrin deposits were seen in serum treated group at 2 days post-injury; at 7 days post-injury the changes revealed moderate fibroplasia, fibrin deposit and severe infiltration of both mononuclear and polymorphonuclear leukocytes; at 14 days post-inju

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Publication Date
Mon Oct 02 2023
Journal Name
Journal Of Engineering
Numerical Analysis of the Stability of Bridge Foundation Pile under Earthquakes Effect
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This study was chosen because of the entry of our regions into the seismic zone recently, where Diyala governorate was hit by the Halabja earthquake in 2017 by 7.3Mw. Therefore, the impact of earthquakes will be studied on the AL-Mafraq bridge foundations piles located in Iraq- east of Baghdad in Diyala Governorate and the extent of its resistance to the Halabjah, EL-Centro, and Kobe earthquakes with acceleration 0.1g, 0.34g, and 0.58g respectively. After modeling and performing the analysis by using Midas Gts-Nx software, the settlement (mm) results at nine nodes (four nodes for the pile cap and five nodes for the piles) were obtained for each of Halabjah, EL-Centro, and Kobe earthquakes to know the resistance of the br

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Publication Date
Thu Apr 01 2021
Journal Name
Iop Conference Series: Earth And Environmental Science
Tourist development of heritage in Algeria: case of the Hypone site -ANNABA-
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Abstract<p>In a world where tourism has become the leading industry on the market, sustainable tourism has found its place and is becoming a major player in the network of traveling Internet users. Hospitality, solidarity and conviviality are essential are giving meaning to sharing. This “extra soul” has the capacity to enrich moments, places, attractions and heritage. Archaeological heritage sites constitute an important factor for the economic and social life of a large number of countries, the development policy came to emphasize the safeguard and the preservation of landscapes and natural or man-made sites, against the attacks which have impoverished the cultural heritage, this heritage </p> ... Show More
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Publication Date
Tue Jan 08 2019
Journal Name
Iraqi Journal Of Physics
Photocatalytic removal of methylene blue dye by using of ZnS and CdS
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Photocatalytic degradation of methylene blue was studied using CdS and ZnS as catalyst. The photocatalytic activity of the specimen was studied by exposing to UV-radiation. The result shows that the degradation efficiency of the dye for CdS micro-particles was 92% after 7 hours and for ZnS micro-particles was 88.29% for the same time interval.

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