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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 Sep 01 2009
Journal Name
Al-khwarizmi Engineering Journal
The Investigation of Monitoring Systems for SMAW Processes
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The monitoring weld quality is increasingly important because great financial savings are possible because of it, and this especially happens in manufacturing where defective welds lead to losses in production and necessitate time consuming and expensive repair. This research deals with the monitoring and controllability of the fusion arc welding process using Artificial Neural Network (ANN) model. The effect of weld parameters on the weld quality was studied by implementing the experimental results obtained from welding a non-Galvanized steel plate ASTM BN 1323 of 6 mm thickness in different weld parameters (current, voltage, and travel speed) monitored by electronic systems that are followed by destructive (Tensile and Bending) and non

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Publication Date
Fri Sep 01 2023
Journal Name
Iraqi Journal Of Physics
Investigation of Numerical Simulation for Adaptive Optics System
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In this study, the performance of the adaptive optics (AO) system was analyzed through a numerical computer simulation implemented in MATLAB. Making a phase screen involved turning computer-generated random numbers into two-dimensional arrays of phase values on a sample point grid with matching statistics. Von Karman turbulence was created depending on the power spectral density. Several simulated point spread functions (PSFs) and modulation transfer functions (MTFs) for different values of the Fried coherent diameter (ro) were used to show how rough the atmosphere was. To evaluate the effectiveness of the optical system (telescope), the Strehl ratio (S) was computed. The compensation procedure for an AO syst

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Publication Date
Sun Jun 21 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation and Investigation of Lacidipine as a Nanoemulsions
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Many pharmaceutical molecules have solubility problems that until yet consist a hurdle that restricts their use in the pharmaceutical preparations. Lacidipine (LCDP) is a calcium-channel blocker with low aqueous solubility and bioavailability.

        Lipid dosage forms are attractive delivery systems for such hydrophobic drug molecules. Nanoemulsion (NE)  is one of the popular methods that has been used to solve the solubility problems of many drugs. LCDP was formulated as a NE utilizing triacetin as an oil phase, tween 80 and tween 60 as a surfactant and ethanol as a co-surfactant. Nine formulas were prepared, and different tests performed to ensure the stability of the NEs, such as thermodyna

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Publication Date
Thu Dec 29 2016
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Comparison Between Two Approaches (MLE &DLS) to Estimate Frechet Poisson Lindley Distribution Compound by Using Simulation
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  In this paper simulation technique plays a vital role to compare between two approaches Maximum Likelihood method and Developed Least Square method to estimate the parameters of Frechet Poisson Lindley Distribution Compound. by coding using Matlab software program. Also, under different sample sizes via mean square error. As the results which obtain that Maximum Likelihood Estimation method is better than Developed Least Square method to estimate these parameters to the proposed distribution.

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Publication Date
Tue Dec 31 2019
Journal Name
Journal Of Economics And Administrative Sciences
A Try to combine more than approaches and competitive strategies to achieve a sustainable competitive advantage.
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The objective of this research paper is two-fold. The first is a precise reading of the theoretical underpinnings of each of the strategic approaches: "Market approach" for (M. Porter), and the alternative resource-based approach (R B V), advocates for the idea that the two approaches are complementary. Secondly, we will discuss the possibility of combining the two competitive strategies: cost leadership and differentiation. Finally, we propose a consensual approach that we call "dual domination". 

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Publication Date
Thu May 04 2023
Journal Name
Journal Of Communicable Diseases
Enhancement of Swarming and Inhibition of Prodigiosin in Serratia marcescens by Glyceryl Trinitrate
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Introduction:Serratia marcescens is a gram-negative pathogen of many species. Its pathogenicity and survival are linked to its capacity to build biofilms as well as its strong inherent resistance to antimicrobials and cleaning agents. Objectives: To analyse the impact of glyceryl trinitrate (GTN) on the gene expression of QS-related genes (rssB, rsmA,and pigP) of S. marcescens. Methodology: The broth microdilution technique estimated the bactericidal effectiveness of glyceryl trinitrate. The presence of rssB, rsmA,and pigP in S. marcescens isolates was detected using PCR. qRT-PCR was used to assess the effect of GTN on rssB, rsmA,and pigPgene expression. Results: The results demonstrated that GTN has no effect on S. marcesce

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Publication Date
Wed Jun 01 2022
Journal Name
Journal Of The College Of Languages (jcl)
Innovative approaches to the development of the lexical composition of the oil and gas industry : Инновационные подходы развития лексического состава нефтегазовой промышленности
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 The present study discusses one of the most relevant and required topics in the recent period during globalization, the modern Russian system of terms for the oil and gas industry as a whole acquired a complete form in the second half of the twentieth century. The period of the late XX - early XXI centuries. marked by cardinal transformations in all areas of the political, economic, social and cultural life of Russia. These changes could not but affect industrial production. Transition to a new vector of development of the Russian economy based on the development of commercial trade, on the change and improvement of the development of industrial enterprises in the context of the implementation of national projects and the introduction

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Publication Date
Mon Mar 01 2021
Journal Name
Iop Conference Series: Materials Science And Engineering
Speech Enhancement Algorithm Based on a Hybrid Estimator
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Abstract<p>Speech is the essential way to interact between humans or between human and machine. However, it is always contaminated with different types of environment noise. Therefore, speech enhancement algorithms (SEA) have appeared as a significant approach in speech processing filed to suppress background noise and return back the original speech signal. In this paper, a new efficient two-stage SEA with low distortion is proposed based on minimum mean square error sense. The estimation of clean signal is performed by taking the advantages of Laplacian speech and noise modeling based on orthogonal transform (Discrete Krawtchouk-Tchebichef transform) coefficients distribution. The Discrete Kra</p> ... Show More
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Publication Date
Tue Aug 01 2017
Journal Name
International Journal Of Greenhouse Gas Control
CO2 geo-storage capacity enhancement via nanofluid priming
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CO2 geo-storage efficiency is strongly influenced by the wettability of the CO2-brine-mineral system. With decreasing water-wetness, both, structural and residual trapping capacities are substantially reduced. This constitutes a serious limitation for CO2 storage particularly in oil-wet formations (which are CO2-wet). To overcome this, we treated CO2-wet calcite surfaces with nanofluids (nanoparticles dispersed in base fluid) and found that the systems turned strongly water-wet state, indicating a significant wettability alteration and thus a drastic improvement in storage potential. We thus conclude that CO2 storage capacity can be significantly enhanced by nanofluid priming.

Publication Date
Thu Dec 31 2015
Journal Name
Al-khwarizmi Engineering Journal
Hexapod Robot Static Stability Enhancement using Genetic Algorithm
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Abstract

Hexapod robot is a flexible mechanical robot with six legs. It has the ability to walk over terrain. The hexapod robot look likes the insect so it has the same gaits. These gaits are tripod, wave and ripple gaits. Hexapod robot needs to stay statically stable at all the times during each gait in order not to fall with three or more legs continuously contacts with the ground. The safety static stability walking is called (the stability margin). In this paper, the forward and inverse kinematics are derived for each hexapod’s leg in order to simulate the hexapod robot model walking using MATLAB R2010a for all gaits and the geometry in order to derive the equations of the sub-constraint workspaces for each

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