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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
Sat Sep 30 2023
Journal Name
College Of Islamic Sciences
Features of visual formation in the poetry of the poets of the Umayyad era
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Abstract

The Umayyad poets tried to invest all artistic tools in order to achieve a measure of creativity in their texts. The phenomenon of visual composition is breaking the familiar writing system, with the aim of increasing the number of possible connotations. The visual in the Umayyad poetry tries to replace it through expression with the visual image, and its manifestations were manifested by the multiplication of punctuation marks in the body of the poetic text and the tearing of the single poetic line by cutting it into several sentences or repetition.

Keywords: visual formation, poetic writing, Umayyad poetry, recipien

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Publication Date
Sun Aug 25 2024
Journal Name
University Of Samarra
Preparation, diagnosis and testing of the biological ‎activity of new complexes of Schiff bases
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‎ Sixteen new complexes with the general formula [M(L)2(H2O)2] were ‎prepared resulting from the reaction of the two new Schiff base ligands, which ‎are‏: -‏ L1= (E)-5-((2-hydroxybenzylidene)amino)-2-phenyl-2,4-dihydro-3H-pyrazol-3-one)‎ L2 = (E)-5-((2-hydroxy-3-methoxybenzylidene)amino)-2-phenylpyrazolidin-3-one) ‎ ‎ With divalent metal ions (manganese, cobalt, nickel, copper, zinc, cadmium, ‎mercury) and (tetravalent platinum).‎‏ ‏ ‎ Ligands was derived from the reaction of the amine (5-amino-2-phenyl-2,4-‎dihydro-3H-pyrazol-3-one) with Salicylaldehyde and ortho-vanillin, which is ‎linked to the metal ions via the nitrogen atoms are the isomethene group and ‎the oxygen is the hydroxide group of t

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Publication Date
Thu Jun 18 2015
Journal Name
Journal Of Kerbala University
Effect of Carbamazepine drug on formation of decidual tissue in femal of Mus musculus
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Implantation of blastocyst is considered as a sensitive process in the life of growing embryo. Thus this critical period could be under threat from the harmful effect of many drugs ,among them is the carbamazepine which is used by many women for a treatment of epilepsy . The present experiment was designed to study the effect of this drug on the process of implantation ;especially during the days 7 and 9 of pregnancy. For those purpose 169 pregnant albino mice, of 25 gm weight for each one, were used .The mice were divided into control group given orally normal saline, and treated group given orally carbamazepine with concentration of 15 mg\kg. Samples from pregnant uteri containing the embryos were used. They were first fixed in Boun's sol

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Publication Date
Sun Jun 30 2013
Journal Name
Al-khwarizmi Engineering Journal
Effects of Different Types of Fillers on Dry Wear Characteristics of Carbon-Epoxy Composite
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Experimental investigations had been done in this research to demonstrate the effect of carbon fiber and Ceramic fillers contents on the tribological behaviour of (15% volume fraction) carbon-epoxy composite system under varying volume fraction, load, time and sliding distance. The wear resistance were investigated according to ASTM G99-05standard using pin on disc machine to present the composite tribological behaviour. The influence of three ceramic fillers, granite, perlite and calcium carbonate (CaCO3), on the wear of the carbon fabric reinforced epoxy composites under dry sliding conditions has been investigated. The effect of variants in volume fraction, applied load, time and sliding distance on the wear behaviour of po

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Publication Date
Mon Aug 30 2021
Journal Name
Al-kindy College Medical Journal
Quality of Life of Parents of Children with Type I Diabetes Mellitus, Baghdad 2017
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Background: Diabetes is defined by the World Health Organization as a metabolic disorder characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. Families are co-regulating systems in which the stresses and strains of one family member affect the well-being of another member of the family. Caregivers of children with chronic illness report experiencing more parental stress than parents of healthy children.

Objective: A descriptive cross-sectional study had been conducted in four centers of endocrine diseases in Baghdad city and data was collected by using self-administered questionnaire regarding qua

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Publication Date
Wed Nov 07 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Assessment of psychosocial domain of quality of life for women who had undergone hysterectomy
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Abstract A descriptive (cross sectional) study was conducted to assess psychosocial domain of quality of life for (100) women who had hysterectomy for non malignant indications during 6-12 months post operative. The study carried out in both consultation clinics of Al-Elwiya Maternity Hospital and Baghdad Teaching Hospital from January 5th 2003 to July 10th 2003). The results of the study show that hysterectomy achieved a highly successful outcome in terms of psychological and social adjustments for hysterectomies women, a highly significant differences between quality of life (QoL) and some of demographic cha

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Publication Date
Tue Feb 14 2023
Journal Name
Journal Of Educational And Psychological Researches
The Organizational Relaxation of Employees of the Educational Directorates in the Sultanate of Oman
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Abstract

The current research aims to identify the level of organizational relaxation among the employees of educational directorates in the Sultanate of Oman. The descriptive approach was used, as well as a questionnaire of two parts to collect data. The questionnaire consists of (15) items divided into three themes about the relaxing level. It was applied on a sample of (406) male & female employees of the educational directorates who were randomly selected. The results of the study showed that the level of organizational relaxation was low. The study results also found that there were no statistically significant differences at the level of significance (α ≤ 0.05) of the study sample in the level of org

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Publication Date
Thu Aug 27 2026
Journal Name
Al-fatih Journal
Effect of resistance training on the development of marital some elements of physical fitness
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يشهد العالم تقدما في كافة مجالات الحياة المختلفة وتزداد الحياة صعوبة يوما بعد يوم, ويزداد البحث في كافة المجالات التي تعمل على خدمة الإنسان ولقد طال هذا التقدم النشاط الرياضي ,فقد يكون لتطور التدريب الرياضي وتنوع أساليبه الدور الكبير في تحقيق اللياقة البدنية التي تعد إحدى أهم الأهداف التي يرمي إليها الدرس في كلية التربية الرياضية . واللياقة البدنية تستمد أهميتها من كونها إحدى مكونات اللياقة الشاملة التي بدو

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Publication Date
Thu Apr 13 2023
Journal Name
Sustainability
Experimental Study of the Effect of Tack Coats on Interlayer Bond Strength of Pavement
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The performance and lifetime of the flexible asphalt pavement are mainly dependent on the interfacial bond strength between layer courses. To enhance the bond between layers, adhesive materials, such as tack coats, are used. The tack coat itself is a bituminous material, which is applied on an existing relatively non-absorbent surface to ensure a strong bond between the old and newly paved layer. The primary objective of this study was to evaluate the effects of various types of tack coat materials on interlayer bond strength and to determine the optimal application rate for each type. The tack coat types used in this paper were RC-70, RC-250, and CSS-1h. Both laboratory-prepared and field-constructed hot mix asphalt concrete pavements usin

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Publication Date
Mon Feb 27 2023
Journal Name
Chemical Papers
Study of the effect of ionic liquid on the wettability alteration of carbonate reservoir
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