Fluconazole and its cocrystals with maleic and glutaric acids

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Oxidation of drugs during drug product development

Oxidation is the second most common degradation pathway for pharmaceuticals, after hydrolysis. However, in contrast to hydrolysis, oxidation is mechanistically more complex and produces a wider range of degradation productsoxidation is thus harder to control. The propensity of a drug towards oxidation is established during forced degradation studies. However, a more realistic insight into degradation in the solid state can be achieved with accelerated studies of mixtures of drugs and excipients, as the excipients are the most common sources of impurities that have the potential to initiate oxidation of a solid drug product. Based on the results of these studies, critical parameters can be identified and appropriate measures can be taken to avoid the problems that oxidation poses to the quality of a drug product. This article reviews the most common types of oxidation mechanisms, possible sources of reactive oxygen species, and how to minimize the oxidation of a solid drug product based on a well-planned accelerated study

Minimal erythema dose determination in Holstein Friesian cattle

Cattle on pasture are continuously exposed to solar UV radiation, which has been associated with biological effects such as sunburn, photosensitization, squamous cell carcinoma, and cutaneous vitamin D3 production. The minimal erythema dose (MED) required to produce first-degree sunburn (erythema) is poorly researched in cattle. Since cattle are naturally covered with dense hair coats, the MED is influenced by the UV protection offered by the hair. The objective of this study was to determine the MED on intact-hair-covered (MED-H) and shaved white skin (MED-S) of Holstein Friesian cattle. Twenty-one Holstein Friesian cows and heifers were MED tested using a narrowband UV-B LED light (peak irradiance at 292 nm) on eight hair-covered and eight shaved areas over white skin previously unexposed to direct sunlight. Erythema was visually assessed after 24 h. The mean MED-H and MED-S were 5,595 and 329 J/m2, respectively. Heifers had a higher MED-H compared to cows, 7,600 and 4,969 J/m2, respectively. The mean UV transmittance of white cattle hair was 6.7%. MED-H was correlated with hair length (Spearman’s rho = 0.76). A linear regression model showed that each millimeter of hair coat length increased the MED-H by 316 J/m2. In conclusion, this study provides a MED testing protocol for cattle and reports standardized values of MED for cattle on intact-hair-covered and shaved areas

Antimicrobial activity of the marine alkaloids, clathrodin and oroidin, and their synthetic analogues

Marine organisms produce secondary metabolites that may be valuable for the development of novel drug leads as such and can also provide structural scaffolds for the design and synthesis of novel bioactive compounds. The marine alkaloids, clathrodin and oroidin, which were originally isolated from sponges of the genus, Agelas, were prepared and evaluated for their antimicrobial activity against three bacterial strains (Enterococcus faecalis, Staphylococcus aureus and Escherichia coli) and one fungal strain (Candida albicans), and oroidin was found to possess promising Gram-positive antibacterial activity. Using oroidin as a scaffold, 34 new analogues were designed, prepared and screened for their antimicrobial properties. Of these compounds, 12 exhibited >80% inhibition of the growth of at least one microorganism at a concentration of 50 µM. The most active derivative was found to be 4-phenyl-2-aminoimidazole 6h, which exhibited MIC$_{90}$ (minimum inhibitory concentration) values of 12.5 µM against the Gram-positive bacteria and 50 µM against E. coli. The selectivity index between S. aureus and mammalian cells, which is important to consider in the evaluation of a compound\u27s potential as an antimicrobial lead, was found to be 2.9 for compound 6h

Analogues of the marine alkaloids oroidin, clathrodin, and hymenidin induce apoptosis in human HepG2 and THP-1 cancer cells

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