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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 Oct 31 2019
Journal Name
Al-kindy College Medical Journal
Assessment of efficacy and safety of dapsone gel 5% in the treatment of acne vulgaris
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ABSTRACTBackground : Acne vulgaris is a
common skin disease, affecting more than 85% of
adolescents and often continuing into adulthood.
People between 11 and 30 years of age and up to
5% of older adults. For most patients acne remains
a nuisance with occasional flares of unsightly
comedones, pustules and nodules. For other less
fortunate persons, the sever inflammatory response
to Propionibacterium acnes (P.acnes) results in
permanent
Methods: Disfiguring scars. (1, 2) Stigmata of sever
acne cane lead to social ostracism, withdrawal
from society and severe psychologic
depression (1-4).
Result Pathogenesis of acne Traditionally, acne
has been thought of as a multifactorial disease of
the fo

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Publication Date
Fri Jun 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of the effect of local exogenous application of osteopontin on wound healing in rats
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Background: Wound healing is a complex dynamical interaction between various cell types, the extracellular matrix, cytokines, and growth factors. osteoponetin is a substance that acts as an anti-inflammatory. Aims of study: The study was designed to identify the role of local exogenous applications of osteopontin on wound healing (in cheek skin). Materials and methods: Thirty adult male albino rats weighting an average of (250-300gm) used in this study, incisional wounds were made in the skin of the cheek of rat and they were divided into the following groups: A-Control group: 15 rats treated with 1µ l of normal saline B-Experimental groups: 15 rats treated with topical application of 1µl osteopontin. The scarification of animals we

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Publication Date
Wed Jan 01 2020
Journal Name
Plant Archives J.
Evaluation of the performance of introduced varieties of maize under different planting dates and environments
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Publication Date
Fri Jan 11 2019
Journal Name
Iraqi Journal Of Physics
A study of the effect of nano materials on the physical properties of epoxy composites
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This research studies the effect of addition of some nanoparticles
(MgO, CuO) and grain size (30,40nm) on some physical properties
(impact strength, hardness and thermal conductivity) for a matrix
blend of epoxy resin with SBR rubber. Hand –Lay up method was
used to prepare the samples. All samples were immersed in water for
9 weeks.
The Results showed decreased in the values of impact strength and
hardness but increased the coefficient of thermal conductivity.

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Publication Date
Sat Jan 01 2022
Journal Name
Journal Of Ovonic Research
Effect of dopant of aluminum on the structural and optical properties of NiTsPc thin films
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Publication Date
Wed Jan 30 2019
Journal Name
Journal Of The College Of Education For Women
Awareness of the problem technological poisoning Media of parents of kindergarten children and their teachers
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The childhood stage is considered the most important stage of all the stages through
the human being’s life. In this stage the human being will be more affected by the various
factors that surround him/her. The first five years of his/her life leave a great impact not only
on the human being personality, but also on his/her whole life. Therefore, it is worthwhile tobe concerned with and focus at the raising up and the teaching of the child during the
childhood stage.
The mission of raising up children in this era - the era of globalization and information
bursting or news flooding – has become a very difficult or even an impossible mission.
Furthermore, not only in the Arabic world, but also all over the world, t

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Publication Date
Mon Dec 02 2013
Journal Name
Al-nahrain Journal Of Science
Effect of Magnetized Water on Histological Structure of Heart, Lung and Spleen of Albino Rats
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The aim of the study was to investigate the effect of magnetized water on the histological structure of heart, lung and spleen. For this purpose, twenty five albino rats were divided into five equal groups, the first group was considered as control group. The other groups were given magnetized water with intensity of 250, 750, 1000, 1500 gause every day for 30 days. Then the animals were sacrificed and the histological change on heart, lung and spleen was studied. Histopathology of heart in rats treated with magnetic water with intensity of 250, 750, 1000, 1500 gause showed no clear pathological lesion. Lung section of rats treated with 250 gause of magnetic water showed no pathological lesion, while lung section belongs to rats group given

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Publication Date
Fri Feb 17 2023
Journal Name
Biomass Conversion And Biorefinery
Effect of green synthesis of Fe3O4 nanomaterial on the removal of cefixime from aqueous solution
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In this paper, two types of iron oxide nanomaterial (Fe3O4) and nanocomposite (T-Fe3O4) were created from the bio-waste mass of tangerine peel. These two materials were utilized for adsorption tests to remove cefixime (CFX) from an aqueous solution. Before the adsorption application, both adsorbents have been characterized by various characterizations such as XRD, FTIR, VSM, TEM, and FESEM. The mesoporous nano-crystalline structure of Fe3O4 and T-Fe3O4 nanocomposite with less than 100-nm diameter is confirmed. The adsorption of the obtained adsorbents was evaluated for CFX removal by adjusting several operation parameters to optimize the removal. The optimal conditions for CFX removal were found to be an initial concentration of 40 and 50 m

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Publication Date
Tue Jan 01 2008
Journal Name
J Bagh College Of Dentistry
Assessment of consistency and compressive strength of glass ionomer reinforced by different amount of hydroxyapatite
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Background: Glass ionomers have good biocompatibility and the ability to adhere to both enamel and dentin. However, they have certain demerits, mainly low tensile and compressive strengths. Therefore, this study was done to assess consistency and compressive strength of glass ionomer reinforced by different amount of hydroxyapatite. Materials and Methods: In this study hydroxyapatite materials were added to glass ionomer cement at different ratios, 10%, 15%, 20%, 25% and 30% (by weight). The standard consistency test described in America dental association (ADA) specification No. 8 was used, so that all new base materials could be conveniently mixed and the results would be of comparable value and the compressive strength test described by

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Publication Date
Wed Jan 01 2020
Journal Name
Indian Journal Of Ecology
Impact of ground and foliar application of poultry feathers on growth and yield of potato
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