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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 Mar 01 2023
Journal Name
Baghdad Science Journal
Pharmacokinetic Consideration to Formulate Sustained Release Drugs: Understanding the Controlled Drug Diffusion through the Body Compartment of the Systemic Circulation and Tissue Medium-A Caputo Model
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The aim of this study is to provide an overview of various models to study drug diffusion for a sustained period into and within the human body. Emphasized the mathematical compartment models using fractional derivative (Caputo model) approach to investigate the change in sustained drug concentration in different compartments of the human body system through the oral route or the intravenous route. Law of mass action, first-order kinetics, and Fick's perfusion principle were used to develop mathematical compartment models representing sustained drug diffusion throughout the human body. To adequately predict the sustained drug diffusion into various compartments of the human body, consider fractional derivative (Caputo model) to investiga

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Publication Date
Fri Nov 24 2023
Journal Name
Iraqi Journal Of Science
A new mode for an on-line determination of Amiloride in pure and pharmaceutical preparation using CFIA with homemade Ayah 3SBGRx3- 3D solar cell microphtometer analyzer.
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A new, simple, accurate, fast and sensitive spectrophotometric method has been developed for the analysis of amiloride in pure and pharmaceutical formulations by continuous flow injection analysis. The method was based on the oxidation of the drug with Ce(IV)sulfate in acidic medium to formed a pinkish-red color species which determined using homemade Ayah 3SBGR x3-3D solar cell flow injection photometer. Optimum conditions were obtained using a high intensity green light emitted diode as a source. The linear dynamic range for the instrument response versus amiloride concentration was 0.0005- 10 mmol.L-1 while the L.O.D was of 9.471 ng / sample. The correlation coefficient (r) was 0.9824 while percentage linearity (r2%) was 96.50%. RSD%

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Publication Date
Sun Dec 31 2023
Journal Name
College Of Islamic Sciences
The book Al-Durr Al-Manzoum in the dropping of prayer and fasting by Issa Al-Safti Al-Hanafi, who died in the year (1143 AH)
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At the conclusion of my research for this readiness, I am ready to show the most important results I have reached, of which I can mention the most important:
Sheikh Al-Safti was a memorizer and jurist, and all the scientific strokes that he left behind for subsequent generations were in the disciplines of Hanafi jurisprudence, and this does not obscure the opinions of the jurists of other schools of thought. But among them: that these lines continue on a group of fatwas for the later in the gold of Abu Hanifa, may God have mercy on him, and then the books of fatwas usually refer to what is below the evidence.

He has no shock other than the knowledge of jurisprudence; And for this reason, it is due to the fact that the s

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Publication Date
Wed Feb 01 2023
Journal Name
Health Science Reports
Diagnostic potential of salivary interleukin‐17, RANKL, and OPG to differentiate between periodontal health and disease and discriminate stable and unstable periodontitis: A case‐control study
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Abstract<sec><title>Background and Aims

Limitations of the conventional diagnostic techniques urged researchers to seek novel methods to predict, diagnose, and monitor periodontal disease. Use of the biomarkers available in oral fluids could be a revolutionary surrogate for the manual probing/diagnostic radiograph. Several salivary biomarkers have the potential to accurately discriminate periodontal health and disease. This study aimed to determine the diagnostic sensitivity and specificity of salivary interleukin (IL)‐17, receptor activator of nuclear factor‐κB ligand (RANKL), osteoprotegerin (OPG), RANKL/OPG for differentiating (1) periodontal health from disease and (2) stable a

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Publication Date
Mon Oct 30 2023
Journal Name
Iraqi Journal Of Science
Silver nanoparticles synthesized by three species of genus Streptococcus and evaluate their synergistic effects with the oil extracted from Syzygium Aromaticum on some clinical bacterial isolates
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Silver nanoparticles synthesized by different species

Publication Date
Fri Jun 12 2015
Journal Name
Chemistry And Materials Research
Synthesis, Physico-Chemical and Antimicrobial Activities Co(II),Ni (II) ,Cu(II), Zn(II),Cd(II) and Hg(II) MixedLigand Complexes of L- Alanine and Trimethoprim Antibiotic
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The Co (II), Ni (II) ,Cu(II), Zn(II) ,Cd(II) and Hg(II) complexes of mixed of amino acid (L-Alanine ) and Trimethoprim antibiotic were synthesized. The complexes were characterized using melting point, conductivity measurement and determination the percentage of the metal in the complexes by flame (AAS). Magnetic susceptibility, Spectroscopic Method [FT-IR and UV-Vis]. The general formula have been given for the prepared mixed ligand complexes [M(Ala)2(TMP)(H2O)] where L- alanine (abbreviated as (Ala ) = (C5H9NO2) deprotonated primary ligand, L- Alanine ion .= (C5H8NO2-) Trimethoprim (abbreviated as (TMP ) = C10H11N3O3S M(II) = Co (II),Ni(II) ,Cu(II), Zn(II) ,Cd(II) and Hg(II). The results showed that the deprotonated L- Alanine b

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Publication Date
Thu Jan 04 2024
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The Impact of Performance Auditing Process Pursuant to the Programs and Policies Guide in improving the health insurance Prosperity: applied research in the Iraqi General Insurance Company
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Abstract

              The research’s goal lies in demonstrating the impact of the Federal Financial Supervision Endowment through the process of auditing the performance of the entities subject to its audit as to improve the performance of these entities, especially if the performance audit method is one of the newly applied methods that are compatible with the standards issued by the International Organization of Financial Supervision and Accounting Institutions which is the method of auditing performance according to the performance evaluation guide for programs and policies issued by the Federal Office of Financial Supervision.

 T

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Publication Date
Thu Nov 30 2023
Journal Name
Iraqi Geological Journal
Multiple and Coherent Noise Removal from X-Profile 2D Seismic Data of Southern Iraq Using Common Depth Point Muting Procedures and Depending on Madagascar Open-Source Package
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This article describes how to predict different types of multiple reflections in pre-track seismic data. The characteristics of multiple reflections can be expressed as a combination of the characteristics of primary reflections. Multiple velocities always come in lower magnitude than the primaries, this is the base for separating them during Normal Move Out correction. The muting procedure is applied in Time-Velocity analysis domain. Semblance plot is used to diagnose multiples availability and judgment for muting dimensions. This processing procedure is used to eliminate internal multiples from real 2D seismic data from southern Iraq in two stages. The first is conventional Normal Move Out correction and velocity auto picking and

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Publication Date
Sun Sep 01 2019
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
The Investment portfolio risks of the insurance company and their impacts on profitability ratios: An applied research at the national insurance co. for the period 2004-2014
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The research is trying to identify the investment portfolio risks of the insurance company and their impact, on the Profitability ratios of the company, and whether the company's scientific methods followed in the measurement of these risks, and conducted research in the National Insurance Company. by relying on its annual budget as well as the annual reports, The search dealing with these data in theoretical and practical major premise to statistically significant between to investment portfolio risk and financial performance correlation and reach a set of conclusions and recommendations which are the following.                

investments include many ri

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Publication Date
Mon Mar 10 2025
Journal Name
Journal Of Baghdad College Of Dentistry
A Clinical Method for Prediction of Alveolar Bone Mineral Density in the Area between the Second Premolar and First Molar in Iraqi Adults with Class I Occlusion
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Background: Orthodontic mini-implants are increasingly used in orthodontics and the bone density is a very important factor in stabilization and success of mini-implant. The aim of this study was to observe the relationship among maximum bite force (MBF); body mass index (BMI); face width, height and type; and bone density in an attempt to predict bone density from these variables to eliminate the need for CT scan which have a highly hazard on patient. Materials and Methods: Computed tomographic (CT) images were obtained for 70 patients (24 males and 46 females) with age range 18-30 years. The maxillary and mandibular buccal cortical and cancellous bone densities were measured between 2nd premolar and 1st molar at two levels from the alveol

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