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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 Jul 01 2004
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
MICROFACIES ANALYSIS OF GHAR FORMATION (WESTERN DESERT OF IRAQ)
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Ghar Formation outcrop at the Iraqi western desert was studied by microfacies analysis
of (13) thin sections collected from wadi Al-Ratgha ( west of Qaim ) . According to
petrographic com position and organisms content ,rocks were subdivided into (4)
microfacies units :bioclastic wackestone , mudstone , miliolids wackestone , and grainstone
with aggregate grains microfacies .Microfacies units reflect shallow marine environment of
low circulation of very warm water at the middle part . The lower and middle part
interbedded with quite open marine environment below the wave base . The upper part was
deposited at shallow marine environment of low circulation . The main diagenetic processes
were the transformation ( ty

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Publication Date
Thu Dec 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.

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Publication Date
Sun Sep 04 2016
Journal Name
Baghdad Science Journal
Study of the Immunological Status of Iraqi Vitiligo Patients
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Vitiligo is an acquired idiopathic skin disorder characterized by depigmented macules due to loss of cutaneous melanocytes. A potential role of the immune dysfunction has been suggested in vitiligo, so to test this hypothesis, certain cytokines (IL-17A and TNF-?) and immunoglobulins (IgM, IgG, IgA and total IgE) were investigated in all participants. The study included: 60 patients with age range between (6-55) year; 30(11 males and 19 females) were untreated and 30(12 males and 18 females) were treated with Narrow Band Ultraviolet-B (NB-UVB) and 30 (14 males and 16 females) apparently healthy control. Serum was separated and cytokines (IL-17A and TNF-?) and total immunoglobulin E (IgE) were detected by using Enzyme Linked Immunosorbent Ass

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Publication Date
Sun Jan 01 2023
Journal Name
8th Engineering And 2nd International Conference For College Of Engineering – University Of Baghdad: Coec8-2021 Proceedings
Overview of seismic performance assessment of reinforced concrete buildings
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Publication Date
Sat Oct 16 2021
Journal Name
Journal Of Advance Research In Chemical Sciences
Study of Schiff Bases Complexes of Trimethoprim: A Review
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Fri Jun 20 2025
Journal Name
Bulletin Of The Iraq Natural History Museum
A SURVEY OF GASTROPODS IN THE GREENHOUSES OF IRAQ
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The humid and warm conditions in greenhouses provide an excellent environment for pests’ living conditions, and therefore, they provide ideal medium for alien introductions. Molluscs are among the most significant pests that infest plastic covered greenhouses. To identify and report their mollusc species, 23 greenhouses in Iraq were surveyed between March 2023 and April 2024. Of these, 11 were found to be infested with snails. A total of 158 specimens were collected and morphologically identified to seven species: Monacha obstructa (L. Pfeiffer, 1842), Eobania vermiculata (O.F. Müller, 1774), Xeropicta krynickii (Krynicki, 1833), Rumina decollata (Linnaeus, 1758), Polygyra cereolus (Megerle Von Mühlfeld, 1818), Cochlicella barba

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Publication Date
Sun Jan 01 2006
Journal Name
J Bagh College Of Dentistry
Assessment of diametral tensile strength and microhardness of Glass ionomer reinforced by different amounts of Hydroxyapatite
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Back ground: Glass ionomer materials lack resistance to wear and pressure and are susceptible to moisture during the initial stages of setting and dehydration. So this study was done to assess diametral tensile strength and microhardness of glass ionomer reinforced by different amounts of hydroxyapatite. Materials and methods: In this study a hydroxyapatite material was added to glass monomer cement at different ratios: 10%, 15%, 20%, 25% and 30% (by weight). The diametral tensile strength test described by the British standard specification for zinc polycarboxylate cement was used in this study and the microhardness test was performed using Vickers microhardness testing machine and the microhardness values were calculated and statistical c

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Publication Date
Wed Jun 29 2022
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Periodicals Of Engineering And Natural Sciences (pen)
The impact of the internet of things on information institutions from the perspective of library employees
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Fri Nov 01 2013
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International Journal Of Advanced Research
The effects of alkaloid extracted of Solanum nigrum leaves on the biological performance of Dialerodus citri
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Publication Date
Wed Sep 29 2021
Journal Name
College Of Islamic Sciences
The position of Al-Jassas (D. 370 AH) of the verses of "As-Sifat Al-Khbriya"
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This research aims at know the position of Al-Jassas Al- Hanafi (D. 370 AH) of  "As-Sifat Al- Khbriya", through his interpretation: (the provisions of Qur'an), by studying his interpretation of the verses related to this issue.

The most significant results of this study that Al-Jassas did not consider the words that called: "As-Sifat Al- Khbriya" as adjectives to Allah almighty, but he consider them contained an inappropriate meaning to Allah almighty, thus it must be referred to the perfect arbitrator, so he was believe in opinion of interpretation. and interpretations of Al-Jassas for the related of the Qur'an verses relat

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