Current Trends on Solid Dispersions:Past, Present, and Future

Solid dispersions have achieved significant interest as an effective means of enhancing the dissolution rate and thus the bioavailability of a range of weakly water-soluble drugs. Solid dispersions of weakly water-soluble drugs with water-soluble carriers have lowered the frequency of these problems and improved dissolution. Solid dispersion is a solubilization technology emphasizing mainly on, drug-polymer two-component systems in which drug dispersion and its stabilization is the key to formulation development. Therefore, this technology is recognized as an exceptionally useful means of improving the dissolution properties of poorly water-soluble drugs and in the latest years, a big deal of understanding has been accumulated about solid dispersion, however, their commercial application is limited. In this review article, emphasis is placed on solubility, BCS classification, and carriers. Moreover, this article presents the diverse preparation techniques for solid dispersion and gathers some of the recent technological transfers. The different types of solid dispersions based on the carrier used and molecular arrangement were underlined. Additionally, it summarizes the mechanisms, the methods of preparing solid dispersions, and the marketed drugs that are available using solid dispersion approaches

Assessment Practices of Eighth Grade Mathematics

The study aimed at analyzing assessment practice Yarmouk University es that was included in the results of the Jordanian sample of the eighth grade mathematics and science teachers who participated in TIMSS 2011 . The Jordanian sample consisted of (7694) students, (240) mathematics teachers, and of (237) science teachers. To achieve the goals of the study, the responses of both teachers and students to certain items of the questionnaire that were related to assessment practices and included in TIMSS 2011 were analyzed. The results of the study showed that there were differences in teachers and students\u27 estimates to the frequency of homework, with students’ estimates higher than the teachers’ estimates. However, there was consistency in their perception of the time spent to accomplish the homework in both mathematics and science. The study revealed that the time spent on homework exceeded the accepted international criterion. Results revealed that the tests of mathematics had focused mainly on applying mathematical procedures, while in science; they are focused on applying conceptual knowledge. The study recommended that teachers should be aware of the type of questions raised by the TIMSS and the need to learn from the experiences of countries with high performance especially in assessment practices to take advantage of them

Examining the Effect of College Type, Study level, and Gender of Students on Their Use of Teamwork Skills as They Perceived at Yarmouk University of Jordan

The purpose of this study is to investigate whether there is a statistical significant difference in ratings of teamwork skills between students as they perceived based on type of college, study level, and gender variables. A total of 270 students from Yarmouk University participated in the study. The study shows a strong to moderate significant correlation between all six dimensions of teamwork skills. In addition, the study shows a significant difference in interpersonal and communication skills related to gender. Furthermore, the study shows a significant statistical difference in adaptability and coordination skills related to college type. Finally, the findings are discussed and educational implications are provided.Key words: Soft Skills; Teamwork skills; Colleges' Students Skill

Cysteines and Disulfide-Bridged Macrocyclic Mimics of Teixobactin Analogues and Their Antibacterial Activity Evaluation against Methicillin-Resistant Staphylococcus Aureus (MRSA)

Teixobactin is a highly potent cyclic depsipeptide which kills a broad range of multi-drug resistant, Gram-positive bacteria, such as Methicillin-resistant Staphylococcus aureus (MRSA) without detectable resistance. In this work, we describe the design and rapid synthesis of novel teixobactin analogues containing two cysteine moieties, and the corresponding disulfide-bridged cyclic analogues. These analogues differ from previously reported analogues, such as an Arg10-teixobactin, in terms of their macrocyclic ring size, and feature a disulfide bridge instead of an ester linkage. The new teixobactin analogues were screened against Methicillin-resistant Staphylococcus aureus and Methicillin-sensitive Staphylococcus aureus. Interestingly, one teixobactin analogue containing all l-amino acid building blocks showed antibacterial activity against MRSA for the first time. Our data indicates that macrocyclisation of teixobactin analogues with disulfide bridging is important for improved antibacterial activity. In our work, we have demonstrated the unprecedented use of a disulfide bridge in constructing the macrocyclic ring of teixobactin analogues

Cysteines and Disulfide-Bridged Macrocyclic Mimics of Teixobactin Analogues and Their Antibacterial Activity Evaluation against Methicillin-Resistant Staphylococcus Aureus (MRSA)

Teixobactin is a highly potent cyclic depsipeptide which kills a broad range of multi-drug resistant, Gram-positive bacteria, such as Methicillin-resistant Staphylococcus aureus (MRSA) without detectable resistance. In this work, we describe the design and rapid synthesis of novel teixobactin analogues containing two cysteine moieties, and the corresponding disulfide-bridged cyclic analogues. These analogues differ from previously reported analogues, such as an Arg10-teixobactin, in terms of their macrocyclic ring size, and feature a disulfide bridge instead of an ester linkage. The new teixobactin analogues were screened against Methicillin-resistant Staphylococcus aureus and Methicillin-sensitive Staphylococcus aureus. Interestingly, one teixobactin analogue containing all l-amino acid building blocks showed antibacterial activity against MRSA for the first time. Our data indicates that macrocyclisation of teixobactin analogues with disulfide bridging is important for improved antibacterial activity. In our work, we have demonstrated the unprecedented use of a disulfide bridge in constructing the macrocyclic ring of teixobactin analogues

SYNTHESIS AND STRUCTURE ACTIVITY RELATIONSHIP OF TEIXOBACTIN ANALOGUES

Multi-drug resistant bacteria that are primarily unresponsive towards the available marketed antibiotics presents a threat to global health, leading to an increase in mortality and morbidity rate. Today, more than 700,000 people die annually as a consequence to the bacterial infections. This number is expected to rise to 10 million by 2050. New effective antibiotics are still not available, and few are under development as the return on investment is considered low compared to the medications utilised for chronic diseases such as, asthma, and cancer. According to the World Health Organisation (WHO), the world tends to be moving to the post-antibiotic era in which previously treatable bacterial infections are becoming more fatal. As a result of the global spread of bacterial resistance, the researchers collaborated their effort towards finding alternative antimicrobial agents. Antimicrobial peptides are generated by most of the living organisms as part of their immune system, which makes them an interest to synthetic chemists to produce novel antimicrobials. One such antimicrobial is the recently discovered novel natural product teixobactin, which has showed promising data and known to act as a dual target as its mechanism of action. Teixobactin is a macrocyclic depsipeptide presenting excellent activity against Gram-positive bacteria, by targeting lipid II and III to inhibit bacterial cell wall biosynthesis. Teixobactin consists of a 13 membered depsipeptide macrocycle which is constituted by several proteinogenic and one non-proteinogenic amino acid (Enduracididine). Furthermore, the linear tail of teixobactin also consists of seven amino acids of different configuration. In this research, five different projects were conducted on teixobactin based upon the structure-activity relationship (SAR). Each project encompasses a new design of teixobactin synthesis with a group of teixobactin analogues synthesised according to that protocol. Moreover, each project contains antibacterial study to explore the potency of the newly synthesised teixobactin analogues. The first chapter involves the background of the antibiotics in addition to the challenges it faces currently. Moreover, the first chapter introduces a definition of the antimicrobial peptides, especially teixobactin and its discovery and as well as a comprehensive literature review of the research that has been conducted on teixobactin so far. The second and third chapters present a group of analogues where the natural teixobactin ester bond was replaced by disulphide-bridge or amide bond to understand the role v of the ester bond towards its biological activity. Furthermore, third chapter also shows the effect of macrocycle expansion of the teixobactin on its antibacterial activity. The fourth presents the effect of the inclusion of quaternary and ternary amino compounds to the teixobactin structure, where they are coupled to various suitable positions of teixobactin. The fifth chapter chapter shows the impact of Enduracididine10 replacement by cysteine attached with variable alkyl groups.. The sixth chapter contains twenty-eight new teixobactin analogues with different non-proteogenic amino acids in various tolerable positions to explore the antibacterial activity of teixobactin and further investigate the structure-activity relationship (SAR). The last chapter involves a general summary of the work and perspective related to teixobactin. In summary, synthetic studies based on natural products showing antibacterial activity have been conducted towards the development of a new potent teixobactin analogue. Additionally, this whole new research could be potentially useful to develop a further understanding of SAR study of teixobactin