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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
Mon Dec 18 2017
Journal Name
Al-khwarizmi Engineering Journal
Using Smart Control System to Enhancement the Split Air Conditioning System Performance
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In IRAQ, the air conditioners are the principal cause of high electrical demand. In summer, the outer temperature sometimes exceeds 500C which significantly effects on the A/C system performance and power consumed. In the present work, the improvement in mechanical and electrical performance of split A/C system is investigated experimentally and analytically. In this paper, performance and energy saving enhancement of a split-A/C system was experimentally investigated to be efficiently compatible with elevated temperature weathers. This improvement is accomplished via Smart Control System integrate with Proportional-Integral- Differential PID algorithm. The PIC16F877A micro-controller has been programmed with the PID and PWM c

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Publication Date
Wed Feb 20 2019
Journal Name
Iraqi Journal Of Physics
A comparison between PCA and some enhancement filters for denoising astronomical images
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This paper includes a comparison between denoising techniques by using statistical approach, principal component analysis with local pixel grouping (PCA-LPG), this procedure is iterated second time to further improve the denoising performance, and other enhancement filters were used. Like adaptive Wiener low pass-filter to a grayscale image that has been degraded by constant power additive noise, based on statistics estimated from a local neighborhood of each pixel. Performs Median filter of the input noisy image, each output pixel contains the Median value in the M-by-N neighborhood around the corresponding pixel in the input image, Gaussian low pass-filter and Order-statistic filter also be used.

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Thu Feb 01 2018
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Iet Signal Processing
Signal compression and enhancement using a new orthogonal‐polynomial‐based discrete transform
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Thu Feb 07 2019
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Evaluation of Low Level Laser Therapy using 785 nm Diode Laser on the Enhancement of Chronic Wound Healing
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Low-intensity laser irradiation has been explored as an alternative, non-invasive method to encourage chronic wounds to heal. This study aimed to evaluate the effects of low level laser therapy (biostimulation) using semiconductor diode laser with wavelength (785 nm) on the enhancement of chronic wound healing. Fifty patients with chronic wounds were selected to be treated with Low Level Laser Therapy. Their ages ranged between 1 to 76 years. The wound sites were distributed in the lower limb, upper limb, trunk , perineum and head (70%,14%,12%,2%,2%, respectively). Application of laser therapy by noncontact method few millimeters from the skin for 15 minutes per one session twice weekly for two months ; ie,16 sessions for each patient. R

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Thu Nov 01 2018
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Novel Application of Platelet-Rich Fibrin as a Wound Healing Enhancement in Extraction Sockets of Patients Who Smoke
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The Effectiveness of a Developed Unit in The Arabic Language Textbook for The Enhancement of 21st Century Skills
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Abstract

This research aims to develop a unit as part of a sixth-grade Arabic language textbook and measure its effectiveness in the development of twenty-first-century skills of female students. The author adopted the experimental approach with a quasi-experimental design of the pre-post single-group. A list of the major skills was derived from the framework for the 21st-century skills of the mother tongue that was developed by the Partnership for 21st-Century Skills and reviewed and adjusted by some specialists. According to their views, the unit was developed. The study targeted 15 sub-skills falling under three main skills. The results of the study showed the effectiveness of the developed unit in the develo

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Publication Date
Thu Dec 09 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Preparation and In vitro Characterization of Aceclofenac Nanosuspension (ACNS) for Enhancement of Percutaneous Absorption using Hydrogel Dosage Form
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         Aceclofenac (AC) is an orally active phenyl acetic acid derivative, non-steroidal anti-inflammatory drug with exceptional anti-inflammatory, analgesic and antipyretic properties. It has low aqueous solubility, leading to slow dissolution, low permeability and inadequate bioavailability. The aim of the current study was to prepare and characterize AC-NS-based gel to enhance the dissolution rate and then percutaneous permeability. NS.s were prepared using solvent/antisovent precipitation method at different drug to polymer ratios (1:1, 1:2, and 1:3) using different polymers such as poly vinyl pyrrolidone (PVP-K25), hydroxy propyl methyl cellulose (HPMC-E5) and poloxamer® (388) as stabilizer

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Publication Date
Sat Oct 28 2023
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Synthesis and investigation of structural and optical properties of CdO: Ag nanoparticles of various concentrations
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This study discussed the effects of doping with silver (Ag) on the optical and structural properties of
CdO nanoparticles at different concentrations 0, 1, 2, 3, 4, 5 wt% prepared by the precipitation method. The
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The results show that the average diameter of the grains depends on the percentage of added silver to the
material, as the diameter decreased from 88.8 to 59.7 nm, and it was found that the roughness increased from
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Mon Jul 01 2013
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2013 35th Annual International Conference Of The Ieee Engineering In Medicine And Biology Society (embc)
A preliminary investigation of the effect of force variation for myoelectric control of hand prosthesis
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Publication Date
Wed May 01 2019
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Investigation of nanostructured and gas sensing of tin dioxide films prepared by oxidation of Sn
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