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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
Wed Jan 30 2013
Journal Name
Al-kindy College Medical Journal
The Role of Glucosamine Chondrotin Sulfate in the Treatment of Osteoarthritis of Knee
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Background: Osteoarthritis (OA) currently seems
inevitable and unavoidable for a large swath of the
population .its etiology relates to a strong ,but
complex ,non mendelian genetic basis ,combined
with mechanical and metabolic factors that cause
molecular alterations the end results of which
affect the whole joint .Glucosamine and
chondrotin sulfate alone or in combination may be
of benefit to a subgroup of individuals who have
knee pain due to OA.
Glucosamine has been shown to alter cartiage turn
over in patients with OA undergoing physical
training
Aim of the study: To find the validity of
glucosamine chondrotin sulfate in treatment of
grade 1 and 2 OA.
Methods: the sample of 280 patients

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Publication Date
Fri Mar 01 2019
Journal Name
Al-khwarizmi Engineering Journal
Effect of Flaring Angle of Transition Structure On the Scouring of outlet structure
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The transition structure is considered as the most important hydraulic structure controlling the w/s transtion, morever it decrease the scouring of outlet structure.

seven experiment samples for transition structure was used in this research at different angles ( 10° - 90° ).

       It was shown that froud number has a clear effect on the depth of the scouring, morever the high discharge rates cause an increase of the ratio between the length of the scour and its depth.

       In order to select the best flaring angle it was shown that the angle of 40° has the most discharge rate, least structure length and least angle scour depth, with the firmly of t

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Publication Date
Wed Dec 30 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Assessment of Quality of Life in a Sample of Iraqi Patients with Psoriasis.
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Psoriasis is a dermatological, chronic, immune-mediated condition. Psoriasis symptoms are not associated with physical burden only, but it may also have psychosocial effects on patients, diminished cognitive control, poor body image and impairments in everyday life. The value of quality of life is important since improving it is the principal goal for non-curative disease. The aim of the current study was to evaluate quality of life in a sample of Iraqi patients with psoriasis. This study is a cross-sectional study that involved 300 already diagnosed psoriasis patients who attended to the center of Dermatology and Venereology, Medical City/Baghdad. The mean age of patients was (35.156 ±10.549 years). The Arabic version of Dermatology Li

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Mon Jun 01 2015
Journal Name
Journal Of Economics And Administrative Sciences
Experience of Kurdistan province of Iraq in light of the development of economic and social indicators for sustainable development
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Reflect the sustainable development of the interaction of three key elements are the economic component and the social component and the environmental component while focusing economic component to achieve economic growth and focuses social element to achieve social justice in the distribution of income and achieve prosperity, the environmental component related fields and including emphasizes the protection of the environment and to ensure the continuation and sustainability of resources physical, biological and form in which it believes the interaction required for development process real and effective and sustainable, and is considered the province of Kurdistan Iraq of important areas where the movement of developmental mount

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Sun Dec 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
Organizational monitoring and reflex of suffacation of work . An opinions study of sample workers in manufacturing of Isphelt dohuk
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The study aims to determine the organizational monitoring mechanism in target organization as well as knowing the suffocation of work. The study depends on a questionnaire as a tool of collecting data on distributed random sample involved (45) person from different   levels in manufacturing isphelt Dohuk. The study depends on some hypothesis, the most significant one is that there is not impact of organizational monitoring of suffocation especially on the target organization.

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Publication Date
Thu Feb 13 2020
Journal Name
Energies
Impact of the Type of Fertilization and the Addition of Glycerol on the Quality of Spring Rape Straw Pellets
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This paper presents an analysis of selected qualitative characteristics of pellets produced from rape straw obtained from cultivations subjected to different fertilization treatments and from mixtures of straw selected for testing with crude glycerol obtained as a by-product from biodiesel production. The assessment focused on the following qualities of the obtained pellets: Moisture content, mechanical durability, heating value and main elements, that is, carbon, hydrogen, nitrogen, sulphur, chlorine and oxygen. The obtained results indicated that the different treatment regimens applied in spring rape cultivations had a significant impact on the physicochemical qualities of the straw. In terms of the heating value, traditional fer

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Sat Sep 30 2023
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Challenges of Spreading the Culture of Peace in Iraq from the point of view of Leaders and Intellectuals Elites
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The research problem lies in identifying the challenges facing spreading the culture of peace in Iraq, and the most important factors of its instability from the point of view of leaders and intellectual elites.The research derives its importance from the fact that the peace imposed by justice leads to a stable Iraq and a prosperous future.

The study aims to identify the most prominent challenges and obstacles created by wars and faced the process of spreading the culture of peace and instability in Iraq, and to shed light on the reasons leading to the employment of the capabilities of community leaders in spreading the culture of peace.The objective of the current research is to identify the challenges of spreading the culture o

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Publication Date
Sun Sep 01 2013
Journal Name
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Derivative Zero - Crossing Spectrophotometry Of Binary Mixtures Of Acetyl Acetonates Of Micro – Amounts Of Mn (Ii) And Al (Iii).
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New derivative molecular absorption spectrophotometric methods have been developed for the determination of Al (III) , Mn (II) , individually and binary mixtures . The aim of this model of study is to obtain analytical results characterized by adequate standard of analytical figures of merits through application of derivative Spectrophotometry (dnA/d?n). The two metals acetyl acetonates are chemically stable and are widely used as catalysts . Where Interferences are probable due to very close or nearby peaks or Summits, the Zero – Crossing derivative measurement technique is used to avoid interfering effects between two metals pairs.

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Publication Date
Thu Mar 30 2017
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Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Effects of Different Concentrations of Melatonin on the Time-course of Nitrite–induced Oxidation of Hemoglobin: In vitro Study
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         Melatonin is a potent scavenger of reactive oxygen species or free radicals like superoxide and hydroxyl radicals. The oxidation of hemoglobin to methemoglobin (meth-Hb) by oxidizing compounds has been widely studied. The present work was designed to evaluate the ability of different concentrations of melatonin to inhibit nitrite–induced oxidation of hemoglobin. Blood samples were obtained from apparently healthy individuals from which erythrocyte hemolysate was prepared. Different concentrations of melatonin (10-9-1.0 mg/ml) were incubated for 10 min with the hemolysate, then to the resultant mixture 1 ml of sodium nitrite (final concentration 0.6 mM) was added, and the

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Publication Date
Sun Apr 02 2017
Journal Name
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Improving performance of the heads of academic departments at the University of Wasit in light of the administrative functions
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            A field study aimed to improve  administrative performance of the Heads of Departments in Wasit University in light of the administrative functions, a questionnaire constructed was c of 38 items, as have been applied during the academic year 2014/2015 to a group of experts from the deans and assistants, professors and heads of departments using the Delphi method by two rounds the adoption rate of 90% and an agreement was numbered 30 experts and study reached important results have been analyzed and discussed according to fields of study, a planning, organization and direction.

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