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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
Fri Jan 01 2010
Journal Name
Bn Al-haitham Journal For Pure And Applied Sciences
Effects of Different Levels of Urea and Superphosphate Fertilizer in Some Growth Characters and the Yield of Fenugreek plant
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جريت التجربة في اصص فخارية سعة كل اصيص 4 كغم تربة في البيت الزجاجي التابع لقسم علوم الحياة/كلية التربية ابن الهيثـــــــــم/جـامعــة بـغداد لموســم النمـو 2008-2009 لدراســة تأثيــر اربعـــة مستويـــــات من سمــــاد اليوريـــا وهي (0, 0.1, 0.2, 0.4) غم/اصيص والتي تعادل (0, 100, 200, 400) كغم/هكتار وثلاث مستويات من سماد السوبر فوسفات وهي (0, 0.1, 0.2) غم/اصيص والتي تعادل (0, 100, 200) كغم/هكتارفي مكونـات الحاصـــل لنبــات الحلبـــة Trigonella foe

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Publication Date
Sun Mar 01 2020
Journal Name
Baghdad Science Journal
The Effect of Alcoholic and Aqueous Extract of Piper nigrum on the Larvae of Culex pipiens molestus Forskal (Diptera:Culicidae)
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          The present study includes the effect of the ethanolic and aqueous extract of Piper nigrum against the third instar of Culex pipiens molestus (Diptera:Culicidae) in different concentrations: 1, 1.5 ppm of ethanolic extracts of Piper nigrum causing 100% mortality of larvae in the second day of treatment, while the concentrations 5% of aqueous extracts of Piper nigrum caused 100% mortality of larvae in the second day of treatment. The concentration 2.5% caused 100% mortality of larvae after four days of treatment. The current study also detected the effect of 0.1% concentration of Piper nigrum aqueous extract. The effect of this concentratio

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Publication Date
Fri Jan 30 2026
Journal Name
Journal Of Baghdad College Of Dentistry
An Evaluation the Effect of Alcohol Presence in Mouth Washes on Force Degradation of Different Configurations of Elastomeric Chains
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Background: Elastomeric chains are one of the most commonly used force delivery systems. They have the ability to exert a continuous force, convenience of use, compatibility to oral environment and cost effectiveness but one of the inherited disadvantages is force degradation. Materials and methods: This in vitro study was designed to evaluate the effect of alcohol presence in mouthwashes on force decay of different configurations of clear elastomeric chains from (Ortho Technology company) which are: closed , short and long under the effect of time at (Initial, 1, 2, 3 and 4 weeks) intervals with exposure to different chemical solutions. A total (540) modules of elastomeric chains of three different types (long, short and closed) trans

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Publication Date
Tue Dec 31 2024
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Assessment of The Impact of Apremilast on Levels of IL-17, IL-23, and Lipids in Obese Psoriatic Patient
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Background: Psoriasis is an immune-mediated inflammatory disease with unknown aetiology that may be associated with the defect in proliferation and differentiation of the keratinocytes related to inflammatory cell infiltration. According to published reports, it is universal in occurrence; its prevalence in different populations varies from 0.1% to 11.8%. Receiving Apremilast resulted in a strong reduction in interleukin 17 and interleukin 23, as well as reduced expression of other inflammatory cytokines and improvement of psoriatic lesions. Objectives: This study aimed to assess the impact of Apremilast on levels of IL-17, IL-23, and lipids in obese psoriatic patients. Methods: Thirty obese patients with psoriasis were included in

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Publication Date
Tue May 28 2024
Journal Name
Plant Science Today
Isolation and identification of hyperin and naringenin from guava cultivated in Iraq and evaluation of cytotoxic activity of hyperin
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The guava plant, Psidium guajava L., serves as proof of the abundant donations of nature, providing a delicious guava fruit; this plant is rich in groups of medicinal and nutritional benefits. Guava belonging to the Myrtaceae family, many previous studies reported many phytochemical constituents in its leaves that have many pharmacological activities and medicinal properties; this study focuses on the isolation, structural elucidation and calculation concentration of flavonoids, assessment of the cytotoxic activityof hyperin from Psidium guajava leaves newly cultivated in Iraq. The isolation process involved the use of thin-layer chromatography (TLC) and preparative high-performance liquid chromatography (PHPLC) and structural eluci

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Publication Date
Sun Sep 06 2015
Journal Name
Baghdad Science Journal
Evaluation of the level of Some Heavy Metals in Tobacco of Domestic and Imported Cigarette Brands Used in Iraq
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Smoking-related diseases can be attributed to the inhalation of many different toxins, including heavy metals, which have a host of harmful health effects. The primary objective of this study was to determine whether local and imported cigarette brands used in Iraq , have they elevated levels of metals or not .Three metals Lead (Pb) , Cadmium (Cd) and Chromium(Cr) were determined in tobacco of seventeen brands of imported cigarettes commonly available in Iraq and three Iraqi domestic cigarettes , which were randomly taken from retail market in Baghdad by using flame atomic absorption spectrometry. The produced data of imported and local cigarette brands were discussed and compared together and with studies from elsewhere .The result

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Publication Date
Wed Apr 01 2020
Journal Name
Diyala Journal Of Medicine
Histological Evaluation of Local Application of Flavonoid Extract of Capparis Spinosa on Wound Healing in Alloxan-Induced Diabetic Rats
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Publication Date
Mon Jan 01 2024
Journal Name
Brazilian Dental Science
Evaluation of flexural strength and degree of conversion of temporary crown materials at different aging periods in artificial saliva
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Objective: Evaluate the effects of different storage periods on flexural strength (FS) and degree of conversion (DC) of Bis-Acryl composite and Urethane dimethacrylate provisional restorative materials. Material and Methods: A total of 60 specimens were prepared from four temporary crown materials commercially available and assigned to four tested groups (n = 15 for each group): Prevision Temp, B&E CROWN, Primma Art, and Charm Temp groups. The specimens were stored in artificial saliva, and the FS was tested after 24 h, 7 d, and 14 d. A standard three-point bending test was conducted using a universal testing machine. Additionally, the DC was determined using a Fourier transform infrared spectroscopy (FTIR) device. The data were analyzed st

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Publication Date
Mon Dec 21 2020
Journal Name
Bulletin Of The Iraq Natural History Museum (p-issn: 1017-8678 , E-issn: 2311-9799)
REVISION OF THE GENUS SINOXYLON DUFTSCHMID, 1825 (COLEOPTERA, BOSTRICHIDAE) WITH NEW RECORD OF SPECIES IN THE MIDDLE OF IRAQ
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In this study; the genus of Sinoxylon Duftschmid, 1825 (Coleoptera, Bostrichidae) was revised. There were 3 species registered in our investigations: S. anale Lesne, 1897; S. ceratoniae (Linnaeus, 1758) and S. muricatum (Olivier, 1790), the last species was redescribed as being found for the first time for the Iraqi faunal insects. Key to the species were constructed and supported by figures of the main diagnostic characters and some morphological features.

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Publication Date
Thu Jun 15 2017
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of the effect of preheating on micro leakage of Class II composites Restoration (A comparative in vitro study)
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Background: The aim of this in vitro study was to evaluate and compare the effect of preheating microleakage among three different filler size composites which include Filtektm Z250 micro hybrid, Z250xt Nano hybrid and nanocomposite Z350xt.  in Class II cavity preparation .

Materials and methods: sixty maxillary first premolars were prepared with class II cavities. Samples were divided into three groups according to material used    group A (FiltekZ250 micro hybrid). Group B(Z250xt Nano hybrid). Group C (nanocomposite Z350xt)and each group divided into two subgroups of ten teeth according to temperature of  composite:

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