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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 Jun 30 2021
Journal Name
College Of Islamic Sciences
The Economic Role of Sultan Al-Nasir Muhammad Ibn Qalawun in Egypt and the Levant Documentary Study through Writings and Inscriptions
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The people lived under Mamluk rule, distress, poverty, famines, oppression of princes, rulers, And their domination and he always wished for a just ruler to relieve his misery, and remove the injustice

from him, so they found in Al-Nasser Mohammed tend to establish justice.

When Al-Nasser ascended the throne of the Sultanate, there was a rise or fall in prices, so he pursued Prices will end and punish those

who come out for it. And you talk about this search for a relationship

Sultan Al-Nasser with the poor classes in society and his keenness to pursue their affairs was compassionate On them, mer

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Publication Date
Thu Dec 31 2020
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Premiums and compensations and their impact on the financial solvency of insurance companies: applied research in the Iraqi General Insurance Company
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The collected premiums and the compensations paid are among the main variables that have a prominent role in determining the level of financial solvency of insurance companies, as the higher the financial solvency of the insurance company, the more attractive it is to the target audience to acquire the company's insurance services.

Hence the importance of the issue of the solvency of insurance companies, as it is one of the critical matters on which the effectiveness of the insurance company and its continuation in the labor market depend.

In this research, we try to clarify the role of collected premiums and compensations paid in determining the level of operational solvency of t

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Publication Date
Mon Sep 25 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Synthesis of New beta-lactam , 2-thioxoimidazolidin-4-one and Imidazole-5-one Derivatives from thiosemicarbazide and Their Biological Activity Study
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        New derivatives of thiosemicarbazide were synthesized by reaction of different aromatic aldehydes and ketones with thiosemicarbazide to give schiff-bases 1(a-d) . schiff-bases have been used for synthesized the thioimidazolidine 2(a-d)  by reaction of schiff-bases with ethyl chloroacetatein in presence of anhydrous sodium acetate that transformed part of it in to Beta-lactam 3(a-b) compounds with phenyl acetic acid and thionyl chloride , The compounds 4(a-b) came from the reactor of 4-bromobenzaldehyde with compounds 2(a-b) , as well as reaction of compounds 2(b-d) with methyl iodide and anhydrous potassium carbonate to give 5 (b-d) , then added  hydrazine hydrate formed 6(b-d) , then

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Publication Date
Wed Jan 01 2020
Journal Name
Colloids And Surfaces A: Physicochemical And Engineering Aspects
Studies on membrane stability and extraction of ciprofloxacin from aqueous solution using pickering emulsion liquid membrane stabilized by magnetic nano-Fe2O3
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Sun Jun 05 2016
Journal Name
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Level and Statistical Distribution of Thyroid Peroxidase and Thyroid Hormones in Iraqi patients with Type1 Diabetes Mellitus at Al-Karkh Side
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Type 1 diabetes mellitus (T1DM) is an autoimmune disease frequently associated with autoimmune thyroid disease (AITD). The study is conducted at the Specialized Center for Endocrinology and Diabetes-Baghdad at Al-karkh side, during December 2013 up to April 2014. In this study, we investigate the prevalence of anti-thyroid peroxidase (anti-TPO) antibody in(80) type1 diabetic patients with (AITD) and (30) healthy controls .Blood samples are taken for investigation of thyroid tests by using Vitek Immunodiagnstic Assay System (VIDAS).Enzeme Linked Immunosorbent Assay (ELISA) is used to detect anti-thyroid antibody(anti-TPO). The results show that age, gender and BMI (body mass index) are similar in both groups, p>0.05. Among 80 type1 diabetic

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Publication Date
Thu Feb 16 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Knowledge, Attitudes, Practices, and Online Distance Learning Experience of Malaysian University Students towards COVID-19: A Cross Sectional Study(Conference Paper )#
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Some new norms need to be adapted due to COVID-19 pandemic period where people need to wear masks, wash their hands frequently, maintain social distancing, and avoid going out unless necessary. Therefore, educational institutions were closed to minimize the spread of COVID-19. As a result of this, online education was adapted to substitute face-to-face learning. Therefore, this study aimed to assess the Malaysian university students’ adaptation to the new norms, knowledge and practices toward COVID-19, besides, their attitudes toward online learning. A convenient sampling technique was used to recruit 500 Malaysian university students from January to February 2021 through social media. For data collection, all students

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Publication Date
Wed Jan 12 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluating the Impact of Pharmacist Counselling for Asthmatic Children at Karbala Teaching Hospital for Children: An Interventional Prospective Study (Conference Paper )#
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Asthma is one of the most common chronic, non-communicable diseases affecting children worldwide. The estimated prevalence of pediatric asthma in Iraq is 15.8%. Physiologic, inflammatory and structural factors contribute to the development of asthma. Assessment and monitoring of asthma control can be done by a validated children asthma control test (CACT). Management of asthma must address three components which are an appropriate management plan, the most appropriate medication if necessary, and the use of safe and effective medication. The management plan should consider patient counseling and education about the definition of asthma, signs, and symptoms, the pathophysiology of asthma, common triggers for asthma and how can avoid them,

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Publication Date
Thu Sep 01 2022
Journal Name
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Experimental evaluation of Carbon Dioxide-Assisted Gravity Drainage process (CO2-AGD) to improve oil recovery in reservoirs with strong water drive
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Publication Date
Sun Dec 22 2019
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Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Ex-vivo Ex-Vivo Absorption Study of a Novel Dabigatran Etexilate Loaded Nanostructured Lipid Carrier Using Non-Everted Intestinal Sac Model
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Abstract

The purpose of our study was to develop Dabigatran Etexilate loaded nanostructured lipid carriers (DE-NLCs) using Glyceryl monostearate and Oleic acid as lipid matrix, and to estimate the potential of the developed delivery system to improve oral absorption of low bioavailability drug, different Oleic acid ratios effect on particle size, zeta potential, entrapment efficiency and loading capacity were studied, the optimized DE-NLCs shows a particle size within the nanorange, the zeta potential (ZP) was 33.81±0.73mV with drug entrapment efficiency (EE%) of  92.42±2.31% and a loading capacity (DL%) of 7.69±0.17%. about 92% of drug was released in 24hr in a controlled manner, the ex-vivo intestinal p

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Publication Date
Wed Jan 01 2020
Journal Name
Indian Journal Of Forensic Medicine And Toxicology
Continuous Flow Injection Analysis,Turbidmetric and Photometric Determination of Methyldopa Using a New Long Distance Chasing Photometer (NAG-ADF-300-2)
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A specific, sensitive and new simple method was used for the determination of methyldopa in pure and pharmaceutical formulations by using continuous flow injection analysis. This method is based on formation of ion pair compound between methyldopa and potassium hexacyanoferrate in acidic medium to obtain a yellow precipitate complex using long distance chasing photometer (NAG-ADF-300-2). The linear range for calibration graph was 0.05-35 mmol/L for cell A and 0.05-25 mmol/L for cell B, and LOD 1.4292 µg /200 µL for both cells with correlation coefficient (r) 0.9981 for cell A and 0.9994 for cell B, RSD% was lower than 0.5 % for n=8 for. The results were compared with classical method UV-Spectrophotometric at λ max=280 nm and turbi

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