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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
Tue Jun 01 2021
Journal Name
Baghdad Science Journal
Removal of Congo Red Dye From Aqueous Solution Using Eco-Friendly Adsorbent of Nanosilica
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            The development of a new, cheap, efficient, and ecofriendly adsorbents has become an important demand for the treatment of waste water, so nano silica is considered a good choice. A sample of nanosilica (NS) was prepared from sodium silicate as precursor and the nonionic surfactant Tween 20 as a template. The prepared sample was characterized using various characterization techniques such as FT-IR, AFM, SEM and EDX analysis. The spectrum of FTIR confirms the presence of silica in the sample, while SEM analysis of sample shows nanostructures with pore ranging (2-100nm).The adsorptive properties of this sample were studied by removing Congo red dye (CR) from aqueous solution. Batch experimental methods were carried o

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Publication Date
Wed Jan 01 2020
Journal Name
Medeniyet Medical Journal
Serum Glial Fibrillary Acidic Protein: A Surrogate Marker of the Activity of Multiple Sclerosis
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Multiple sclerosis (MS) is a neurodegenerative disorder with various clinical types. Glial fibrillary acidic protein (GFAP) is significantly elevated in the cerebrospinal fluid (CSF) of MS patients compared with that of healthy controls. The aim of this study is to evaluate serum levels of GFAP in relation to disease activity in relapsing-remitting MS patients and to compare them with those of healthy controls. Method: This study involved 58 MS patients of relapsing-remitting MS (RRMS) type, 22 in an active stage of the disease and 36 in remission, and 50 healthy individuals as age- and sex-matched controls. Blood samples were taken from the patients at the MS Clinic of the Baghdad Teaching Hospital, and the serum levels of GFAP were determ

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Publication Date
Wed Mar 10 2021
Journal Name
Baghdad Science Journal
Effect of (1,4) phenylenediamine on the corrosion of lead in 1M hydrochloric acid solution
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The accelerating effect of 1,4- phenylenediamine (PDA) additions in 1M hydrochloric acid solution at temperature rang (20-60) C° has been studied by weight losses measurement during ranging time (1-260) h and by following the pb2+ concentration in solution after several times by using Atomic absorption spectroscopy (AAS) . The volume of hydrogen gas involving was followed also in presence and absence of (PDA) in the corrosive solution .Accelerating enhanced by adding (NaCl , NaBr , NaI ) was also investigated.

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Publication Date
Tue Dec 15 2020
Journal Name
Al-academy
Sociology of Pioneers' Theatre Show and Experiences of the Contemporary Youths: سعدية نوري محمد
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The pioneers in the Iraqi theatre were of a great significance in the production of the theatre shows associated with social and political problems, which necessitated a kind of directing that contributed in installing the sociological pillar of the Iraqi theatre, where these shows were close to the traditional realistic shows some of which is soaked with simple symbolism. That could have given it some traits and characteristics which enabled these connotations to determine the type of the theatrical show and the forms of the direction advances according the adopted style by each theatre director, which forms a clear phenomenon in dealing with the ground of the Iraqi social reality and its reflection on the text and the show. The Iraqi t

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Publication Date
Thu Apr 05 2012
Journal Name
مجلة القادسية للعلوم
Effect of some environmental factors on the tolerance of Bacillus subtilis to heavy metals
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Abstract Twelve isolates of bacteria were obtained from samples of different soils and water amended with 100µg/ml of five heavy metals chlorides (i.e: Aluminum Al+2, Iron Fe+2, Lead Pb+2, Mercury Hg+2 and Zinc Zn+2). Four isolates were identified as Bacillus subtilis and B. subtilis (B2) isolate was selected for this study according to their resistance to all five heavy metals chlorides. The ability of B. subtilis (B2) isolate for growing in different concentration of heavy metals chlorides ranging from 200-1200 µg/ml was tested. The highest conc. that B. subtilis (B2) isolate tolerate was 1000 µg/ml for Al+2, Fe+2, Pb+2, and Zn+2and 300 µg/ml for Hg+2 for 24hour. The effect of heavy metals chlorides on bacterial growth for 72 hrs was

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Publication Date
Sun Mar 01 2020
Journal Name
Journal Of Engineering
Effect of Dam Height on The Stability of Earth Dam (Case Study: Karolinka Dam)
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The Karolinka earth-fill dam was constructed between 1977 and 1984 on the Stanovnice river above the town of Karolinka in the region of Vsetínsko in Czech Republic. Because of leakage on the downstream dam face due to technological indiscipline when filling dam layers during the dam construction stage, there were some steps to improve state dam safety. The final rehabilitation is to construct the diaphragm walls from self-hardening cement-bentonite suspension along the length of the dam. In addition to connecting the gallery and abutment (2 × 25 m long) by using jet piles. The article presents numerical modeling of safety factor evaluation associated with the state of the dam body and foundation; before, and after seal

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Publication Date
Fri Jan 01 2021
Journal Name
Wiadomości Lekarskie
EVALUATION THE EFFECT OF PRODIGIOSIN ON ALGD EXPRESSION IN CLINICAL ISOLATES OF PSEUDOMONAS AERUGINOSA
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The aim of this study is to investigate the role of prodigiosin on P. aeruginosa' s biofilm genes involved in the pathogenicity and persistency of the bacteria; Materials and methods: Gram negative bacterial isolates were taken from burn and wounds specimen obtained from some of Baghdad hospitals. Forty six isolates were identified as Pseudomonas aeruginosa and four isolates as Serratia marcescens by using biochemical tests and VITEK 2 compact system. Susceptibility test was performed for all P. aeruginosa isolates, the results showed that 100% were resistant to Amikacin and 98% were sensitive to Meropenem. Resistant isolates were tested for biofilm formation; the strong and moderate isolates (17) were detected by PCR for AlgD gene

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Publication Date
Wed Feb 25 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Effect of systemic administration of Simvastatin on dental implant stability: A random clinical study
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Background: the primary objective for many researches carried out in dental implantology was to reduce the period needed for functional implant loading, simvastatin (cholesterol lowering medication) had many pleiotropic effects, one of which was increasing bone density around titanium implants (1) and subsequently establishing faster osseointegrated dental implants (2,3). This study aims to reduce the period of time needed to establish secondary stability of dental implant measured in ISQ (Implant Stability Quotient) by investigating the effect of orally administered simvastatin on bone. Materials and methods: simvastatin tablets (40mg/day for three months) were administered orally for 11 healthy women aged (40-51) years old who received 1

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Publication Date
Fri Jan 01 2021
Journal Name
Materials Today: Proceedings
Impact of phosphate ester addition on the cytotoxicity of heat cured denture base material
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This study aims to evaluate and compare the cytotoxicity and biocompatibility of a modified heat-cured acrylic denture base material containing 15% phosphoric acid 2-hydroxyethyl methacrylate ester (PA2HEME) with those of nonmodified PMMA. Discs with a diameter of 12 mm and a thickness of 2 mm were prepared using a heat-cured PMMA denture base material and divided into control and experimental groups. The experimental group was modified with 15% phosphoric acid 2-hydroxyethyl methacrylate ester (PA2HEME). The modified and nonmodified materials were tested via FTIR, and the effect of modification on surface roughness was evaluated with AFM. An in vitro test was conducted to examine the cytotoxicity and biocompatibility of heat-cured acry

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Publication Date
Sun Jun 07 2015
Journal Name
Baghdad Science Journal
Determanation of Several Biochemical Parameters in Sera of Iraqi Patients with type 2 Diabetes
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Diabetes mellitus, or simply diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the pancreas does not produce enough insulin, or because cells do not respond to the insulin that is produced. This high blood sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst), and polyphagia (increased hunger). The aim of the study is to measure several biochemical parameters in T2DM patients and the effect of these parameters in development the disease. Laboratory investigations including Ceruloplasmin , fasting blood glucose (FBG) , malondialdehyde (MDA), serum protein, uric acid, and protein electrophoresis have been measured in patients with type

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