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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
Tue Nov 30 2021
Journal Name
Research Journal Of Pharmacy And Technology
Effect of Palliative Radiotherapy in controlling pain of Malignancy
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Background: Radiation therapy reported to be an effective in palliating pain. Objective: To describe roles of palliative radiotherapy in controlling pain in metastatic cancerous patients, and evaluation of radio-therapy doses in pain management. Methods: A prospective observational study carried out at the Baghdad Radiotherapy and Nuclear Medicine Center/Baghdad Medical City Complex, Baghdad, Iraq, from 1st of December 2018 to 30th of May 2019. 88 Patients, were included. Patients were assessed before applying radiotherapy, and at the end of treatment. Pain scoring used from 0 to 10. Kaplan Meier survival curve used. Result: The mean±SD of age was 55.44±11.1 years, and the most frequent age group was 41-50years as 37(42.1%). Breas

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Development of resistance of some klebsiella species isolated locally
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200 samples collected Adrar of patients with urinary tract infection were investigating the types of bacteria most local isolates showed high resistance to antibiotics penicillin c ??????? Amoxicillin Beracelin

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Publication Date
Sun Oct 01 2023
Journal Name
International Science And Technology Journal
Impact of Concentration of Cow MANURE ON Biogas Production
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In Libya, there are multiple sources of pollution, one of which is animal waste. The anaerobic digestion (AD) of organic wastes to produce biogas has the advantage of producing valuable, renewable energy while reducing the environmental impact of these wastes. Cowmanure have the potential to produce biogas due to their high organic content. This study aimed to study different concentrations for the feedstock (1:1 and 2:1 cow manure: water v/v) to monitor which one gives higher biogas production. A plastic tank with a capacity of 72 liters and a feedstock volume of 60 liters was used to create a pilot scale. The biogas was analyzed using a GC device at the end of the experiment in the Zawiya Oil Refining Company. The result indicated that th

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Publication Date
Wed Mar 01 2017
Journal Name
International Journal Of Scientific Research In Knowledge
Monitoring of the Compressibility Characteristics of Asphalt Stabilized Subgrade
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The subgrade soil is the foundation plate form of the roadway; it should sustain its structural characteristics throughout the design life of the roadway with minimal requirements for maintenance. When Gypseous soil is implemented in the construction of subgrade, problems regarding collapsibility and poor structural capacity usually occur when the subgrade came in touch with excess water. Asphalt stabilization could furnish a proper solution to such problems. In this investigation, an attempt has been made to monitor the variations in compressibility characteristics of asphalt stabilized subgrade soil subjected to 30 cycles of (freezing-thawing) and (heating-cooling). Data have been observed after each 10 cycles, and compared with that of r

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Publication Date
Thu Sep 16 2021
Journal Name
Journal Of Advance Research In Chemical Sciences
Study of Schiff Bases Complexes of Trimethoprim: A Review
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Trimethoprim derivative Schiff bases are versatile ligands synthesized with carbonyl groups from the condensation of primary amines (amino acids). Because of their broad range of biological activity, these compounds are very important in the medical and pharmaceutical fields. Biological activities such as antibacterial, antifungal and antitumor activity are often seen. Transition metal complexes derived from biological activity Schiff base ligands have been commonly used

Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
THIAMINE – INDUCED FORMATION OF THE MONOPYRROLE MOIETY OF PRODIGIOSIN
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Thiamine stimulates the production of a red pigment , which is chromatographically and spectrophotometrically identical to prodigiosin , by growing cultures of serratia marcescens mutant 9-3-3 . this mutant is blocked in the formation of 2- methyl -3- amyl pyrorol( MAP),the monopyrrole moiety of prodigiosin , but accumulates 4-methoxy-2, 2-bipyrrole -5- carboxaldehyde (MBC) and can couple this compound with( MAP) to form prodigiosin . Addition of thiamine caused production of( MAP) , and as little as 0.02 mg of thiamine / ml in peptone- glycerol medium stimulated production of measurable amounts of prodigiosin. Phosphate saltes and another type of peptone decreased the thiamine- induced formation of prodigiosin ,yeast extract and glyc

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Publication Date
Fri Feb 08 2019
Journal Name
Journal Of The College Of Education For Women
Variation in the degree of Continentality climate of Iraq
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This research paper is about thevariationin the degree of Continentality climate of the
Iraq during (40) years for a number of climate station. Using Poresof formula, it is found out
that the climate of Iraq ranges between extreme Continentality and very extreme
Continentality, and that the Continentality degree is characterized with extreme frequency
from one year to another. In certain years, the degree of climate Continentality decreases
while in other years it rises in such a way that there is no similarity in the Continental degree
from one year to another for the same station.
As for the general trend of the degree of Continentality, the last years had noticed
special variations, which are divided in to thre

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Publication Date
Mon Dec 01 2014
Journal Name
Journal Of Biotechnology Research Center
Cytotoxicity of myriocin against axenic culture of Leishmania mexicana
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Serine Palmitoyltransferase SPT is the key enzyme in the de novo sphingolipids biosynthesis pathway in eukaryotes, including the intracellular parasite Leishmania. Previous studies showed that this enzyme SPT is expressed only in divided promastigote forms and it is non-essential in the amastigotes form of Leishmania major, which is known as the old world leishmaniasis. In this study we have studied the viability of new world lesihamniasis, Leishmania mexicana. Cytotoxicity test used to determine the effect of the SPT inhibitor myriocin which did not significantly affect the viability of the two forms of the in vitro cultures of the parasite p<0.05, procyclic promastigotes and amastigotes, in which cell viability for miltefosine trea

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Publication Date
Sun Sep 02 2012
Journal Name
Baghdad Science Journal
Product of Conjugacy Classes of the Alternating Group An
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For a nonempty subset X of a group G and a positive integer m , the product of X , denoted by Xm ,is the set Xm = That is , Xm is the subset of G formed by considering all possible ordered products of m elements form X. In the symmetric group Sn, the class Cn (n odd positive integer) split into two conjugacy classes in An denoted Cn+ and Cn- . C+ and C- were used for these two parts of Cn. This work we prove that for some odd n ,the class C of 5- cycle in Sn has the property that = An n 7 and C+ has the property that each element of C+ is conjugate to its inverse, the square of each element of it is the element of C-, these results were used to prove that C+ C- = An exceptio

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Evaluation of Laser Doping of Si from MCLT Measurement
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The measurement of minority carrier lifetime (MCLT) ofp-n Si fabricated with aid of laser doping technique was reported. The measurement is achieved by using open circuit voltage decay (OCVD) technique. The experiment data confirms that the value of MCLT and proftle of Voc decay were very sensitive to the doping laser energy.

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