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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 Nov 30 2023
Journal Name
المجلة العراقية للبحوث الانسانية والاجتماعية والعلمية
Issues of contemporary jurisprudence
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Islamic jurisprudence is a divine approach capable of confronting all developments that occur in human society and giving appropriate solutions to them. The research discussed opinions related to some contemporary issues according to the rule of no excess or negligence and according to the rules of removing hardship and facilitating in order to reach the appropriate legal ruling for the nature of the situation to which it may be exposed. Man is in paradise, and the research emphasizes the necessity of taking into account the aspect of precaution when deciding on issues, such as the rules of change and the removal of embarrassment

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Publication Date
Wed Apr 01 2009
Journal Name
Iraqi Journal Of Science
HOFFMAN INDEX OF MANIFOLDS
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For a connected topological space M we define the homeomorphism and period noncoincidence indices of M, each of them is topological invariant reflecting the abundance of fixed point free self homeomorphisms and periodic point free self maps defined on M respectively. We give some results for computing each of these indices and we give some examples and some results relating these indices with Hoffman index.

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Sun Dec 09 2018
Journal Name
Baghdad Science Journal
On Preradical of Semimodules
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In this paper we study the notion of preradical on some subcategories of the category of semimodules and homomorphisms of semimodules.
Since some of the known preradicals on modules fail to satisfy the conditions of preradicals, if the category of modules was extended to semimodules, it is necessary to investigate some subcategories of semimodules, like the category of subtractive semimodules with homomorphisms and the category of subtractive semimodules with ҽҟ-regular homomorphisms.

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Publication Date
Wed Jul 30 2008
Journal Name
College Of Islamic Sciences
terms of social organization
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The science of interpretation is considered one of the most important sciences due to its primacy and high status. Because knowledge is honored with the honor of its owner and related to it, and the science of interpretation is related to the Book of God, and from this importance emerges the importance of writing on a subject (from the terms of social organization in the Holy Qur’an); Because it deals with a matter that is considered a necessity in a place, and I called the research (from the terms of social organization in the Holy Qur’an - an analytical study), and the reason for choosing this topic was to clarify those terms and link them to our contemporary reality in order for them to be beacons of guidance and guidance for thos

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Publication Date
Sat Jan 01 2022
Journal Name
Science Archives
Medical application of Chitosan
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By using the deacetylation method, chitin is converted into bioproduct chitosan. Deacetylation can be accomplished using chemical or biological mechanisms. Due to its biocompatibility, nontoxicity, biodegradability, natural origin, and resemblance to human macromolecules, it is useful in medicine. Chitosan may have antibacterial and antioxidant properties. Additionally, it could be used in biotechnology, agriculture, gene therapy, food technology, medication delivery, cancer therapy, and other fields. The objective of the current review was to list the most significant applications of Chitosan in the biomedical field.

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Publication Date
Wed Dec 30 2015
Journal Name
College Of Islamic Sciences
Investment of Zakat funds
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Zakat funds may be invested by the owner or his agent, because there is a delay in the investment, and such delay may harm the beneficiaries.
The scholars agreed on the permissibility of investment if it is received from those who are entitled to zakat after it is received, because if zakat reaches their hands, they become wholly owned by them, and therefore they may dispose of it as the disposition of the owners in their property, like all other permissible acts that are permissible according to shariah. What you will see in the folds of the search, God willing).

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Publication Date
Sun Jun 30 2013
Journal Name
Al-kindy College Medical Journal
Huge Chondrosarcoma of Shoulder
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Background: Chondrosarcoma is the second most frequent primary malignant tumor of bone. It is considered relatively an uncommon tumor. Generally it is not common for chondrosarcoma to attend huge size; however, one type was described as mesenchymal chondrosarcoma of low grade cartilaginous cells, with female predominance which can grow to exceptionally large size. Case Presentation: We report a case of Chondrosarcoma, in 30 years old woman of 4 years duration, with a huge mass (weighted 16 Kg) and roughly measured 40x30 x20cm, around the right shoulderInvestigations: Repeated MRI of the shoulder and trunk revealed a clear plane of cleavage between the tumor mass and the chest and abdominal walls and absence of invasion of the abdomen. Ul

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Sun Dec 31 2000
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
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Publication Date
Fri Mar 31 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation of Rifampicin Suspension
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Rifampicin is the drug of choice in treatment of tuberculosis. Also, it is effective in treatment of various bacterial infections.This study was carried out to prepare a stable suspension for rifampicin through preparation of different formulas of rifampicin aqueous suspension either as ready to use or as granular powder to be reconstituted.The selected formula (A) was evaluated and compared with commercial brand of rifampicin (Rifactine®) as a reference through measuring their dissolution rates and other physical properties.The results indicated that the selected formula had better dissolution rate compared with the reference suspension and the rheogram showed that the selected formula was less

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