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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 10 2021
Journal Name
Baghdad Science Journal
Effect of Subinhibitory concentration of Antibiotic on Bacterial Adherence to Orthopedic Prosthetic Device
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The effect of subinhibitory concentration of Antibiotics on the Adherence of S.aureus (Coagulase Positive Staphylococci), and S.epidermidis (Coagulase negative Staphylococci) and Pseudomonas aeruginosa, Enterobacter cloacae, Citobacter freundi (Gram negative bacteria) was done and the results revealed that Rifampicin was the best antibiotic inhibiting Staphylococci adherence and Vancomycin has less effect on the adherence of Staphylococci, whereas Tetracyclin was the best antibiotic inhbiting Gram negative bacteria adherence and Amikacin has the lest less effect on inhibiting bacterial adherence.

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Publication Date
Mon Jan 30 2023
Journal Name
Iraqi Journal Of Science
Detection of mexB Multidrug Efflux Gene in Some Local Isolates of Pseudomonas aeruginosa
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According to the prevalence of multidrug resistance bacteria, especially Pseudomonas aeruginosa, in which the essential mechanism of drug resistance is the ability to possess an efflux pump by which extrusion of antimicrobial agents usually occurs, this study aims to detect the presence of mexB multidrug efflux gene in some local isolates of this bacteria that show resistance towards three antibiotics, out of five. Sensitivity test to antibiotics was performed on all isolates by using meropenem (10μg/disc), imipenem (10μg/disc), amikacin (30 μg/disc), ciprofloxacin (5μg/disc) and ceftazidime (30 μg/disc). Conventional PCR results showed the presence of mexB gene (244bp) in four isolates out of ten (40%). In addition,25, 50μg/ml of cur

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Publication Date
Tue Jan 01 2019
Journal Name
Journal Of Pharmaceutical Sciences & Research
Determination of Some Biochemical Parameters of Acromegalic Patients with Type 2 Diabetes Mellitus.
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Background: Because of the disturbance in the pituitary gland, growth hormone (GH) secretion will be increased and, as a result, insulin-like growth factor 1 (IGF-1) secretion will be increase as well, leading to a chronic and rare disease called acromegaly disease. One of the most serious complications of acromycaly is diabetes. Insulin resistance, which causes diabetes, occurs in the body because of increased growth hormone secretion Objective: The aim of this work is to estimate some biochemical parameters. These parameters were not studied extensively in the literature such as BALP and LOX and the possibility of using LOX as a new biomarker for acromyalgic patients with diabetic. Patients and Methods: The study was performed on (25) mal

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Publication Date
Wed Jun 28 2017
Journal Name
Iraqi Journal Of Science
Antibacterial Activity of Synergistic Effect of Colicin and Gold Nanoparticles Against Pseudomonas Aerugensa
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Publication Date
Sat Nov 27 2021
Journal Name
Route Educational & Social Science Journal
A STYLISTIC ANALYSIS OF ADVERTISING DISCOURSE: A CASE STUDY OF FACEBOOK COMMERCIAL ADVERTISEMENT
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BN Rashid

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Publication Date
Tue Apr 30 2024
Journal Name
Abdulraheem Assi Obaid
Effect of shading net, planting methods and bio-extract on production of muskmelon
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Publication Date
Sun Mar 01 2009
Journal Name
Baghdad Science Journal
The Effect of Sodium Propionate on Microorganism and Self life of Laboratory Biscuit
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This study has been conducted to examin the effect of sodium propionate at different level of 0.03,0.06,0.10% on the number of bacteria and mold and to extend the storage life of laboratory processed biscuit. The results indicated that the use of 0.10% sodium propionate prolonged the storage peroid until the third month, while the use of 0.20% sodium propionate showed no growth of bacteria up to six month of storage, three types of bacteria has been isolated from processed biscuit, namely, Staphylococcus aureus, Bacillus cereus, Esherichia coli. using 0.10% sodium propionate showed no growth of mold up to three month of storage ,while using of 0.15 % and 0.20% sodium propionate prevent the growth

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Publication Date
Sun Mar 04 2012
Journal Name
Baghdad Science Journal
Effect of Fat Replacement with Tahena on the Quality Properties of Shortened Cake
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The objective of this research was to investigate the effect of replacing fat(shortening) with different percentages of tahena on the quality properties (physiochemical and sensory ) of shortened cake.The percentages of moisture,protein ,fat and ash of cake increased significantly(p<0.05) as the replacement was increased .The highest increase percentages were 10,48,5,and 90 %,respectivly, at 100% replacement .Carbohydrate,however,decreased by 10%at 100% replacement .these findings may indicate improvement of cake nutritional value.Standing height,as an indicator of cake volume, also increased significantly by 4% at the 50% replacement then it decreased by 4% 100% replacement level. Basic formula (control) has signific

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Publication Date
Fri Nov 09 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Assessment of the Risk Factors of Coronary Artery Diseases in Al-Nasiriyah City
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Objective: to assess the risk factors of coronary artery disease patients.
Methodology: A non-probability (purposive) sample of (100) patients. The study population consisted of
a sample of adults from both genders whose ages were 30 years and more, and was newly diagnosed as
having CAD by coronary angiography in the cardiac catheterization unit of An Nasiriyah heart center.
Results: The result of the study showed that the most common modifiable risk factors were low HDL-C
levels (58%), smoking (53%), hypertension (46%), diabetes mellitus (34%), obesity (30%), high
triglycerides (19%), hypercholesterolemia (17%), and high LDLC (14%). All these factors were positively
and significantly associated with the development

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Publication Date
Sun Mar 07 2010
Journal Name
Baghdad Science Journal
Identification and Purification of Cholera Like Toxin from Environmental Isolate of Vibrio cholerae
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The presence and prevalence of V. cholerae were investigated in forty five water samples collected from different locations of Tiger River/ Baghdad city. Twenty one isolates were isolated by adopting a simple isolation techniques. The final identification revealed that only three isolates were confirmed as V. cholerae. They were named 1J, 1R and Dial 131 which are all serogrouped as non-O1. Toxin Coregulated Pili (TCP) and heat labile enterotoxin (LT) were determined in only the environmental isolate 1J while non of the isolates produced heat stabile toxin (ST). The purification scheme was improved, few steps were adopted to include back extraction of ammonium sulfate, saturation between 80-20%, desalting through Sephadex G25, and gel filt

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