Flow chemistry has become a vibrant area for research over the past decade. This perspective is intended to capture insights on how these advances have and will continue to impact the development and commercialization of active pharmaceutical ingredients. A series of chemistry examples from a number of pharmaceutical companies will highlight the influence of flow chemistry on this industry.
Twenty-six Bifidobacterium strains were isolated from human faeces. Seven strains were identified as B. bifidum, 4 strains as B. breve, 10 strains as B. longum, 2 strains as B. pseudocatenulatum and 3 strains as B. dentium by 16S rDNA analysis. The isolates from human origin showed strong adherence to the human tissue cultures. Three out of the 12 tested isolates repressed the growth of enteropathogenic bacteria. Utilisation of 9 commercially available oligosaccharides was tested by both Bifidobacteria and enteropathogens. Pro-, pre- and synbiotic food was made. Their effect was evaluated in in vivo feeding experiments, where healthy and antibiotic treated mice were used as test animals. During the four-week feeding period the composition of the colonic microbiota of the healthy mice did not change characteristically in any feeding group. However, the microbiota of mice in which it had been killed by antibiotic treatment was recovered by feeding with synbiotic food.
A TA Instruments Thermal Analysis System (TG) has been interfaced to the Hewlett Packard 5972 quadrupole mass spectrometer.
An OSS-2 variable outlet splitter was plumbed between the TG and the mass spectrometer. This interface allows continuous monitoring
of the ion intensities of mass peaksm/e=18 (water) andm/e=44 (carbon dioxide) used to elucidate the TG transitions attributable to residual moisture in freeze-dried biological products.
Moisture specifications must be met in order to insure product stability throughout the approved shelf life. TG/MS results
are discussed for BCG Vaccine, BCG Live (Intravesical) and U. S. Standard Antihemophilic Factor. Karl Fischer and TG/MS moisture
results are compared.
(TG), thermogravimetry/mass spectrometry (TG/MS), and loss-on-drying methodology
are used to provide residual moisture results for freeze-dried biological
products regulated by the US Food and Drug Administration. Residual moisture
specifications must be met in order to ensure freeze-dried biological product
potency and stability throughout the licensed product's shelf life.
TG, TG/MS, loss-on-drying and vapor pressure moisture measurements are compared
for a BCG Vaccine. Comparisons are made between residual moisture data for
the freeze-dried cake and vapor pressure moisture determinations in the space
above the freeze-dried cake in the final container. Vapor pressure moisture
precision data is presented for α-interferon and BCG vaccine. Impact
of residual moisture and vapor pressure moisture upon product stability is
The adhesion of twenty-six Lactobacillusstrains to two intestinal cell lines (Caco-2P and IEC-18) and 21 Bifidobacteriumstrains to Caco-2P cells was investigated. Non-specific adherence was determined on the surface of culture plates. The effect of short chain fatty acids (SCFA) on epithelial cells, and bacterial adhesion were investigated by Na-n-butyrate treatment. The adherence of LAB and bifidobacteria greatly varied in a strain-dependent manner. The adherence of LAB was better to IEC-18 cells than to Caco-2P cells, and bifidobacteria adhered better to Caco-2P cells than the LAB. Some strains adhered well or even better to the background than to the cells, which queries the specificity of adhesion of these strains. Na-n-butyrate treatment stimulated the differentiation of IEC-18 cells and therefore increased the number of adherent bacteria, probably because only the cell surface increased not the number of epitopes.
The catalytic effects of human superoxide dismutase and bovine ceruloplasmin on superoxide radical dismutation were studied by pulse radiolysis at room temperature. The rate constants for the disappearance of superoxide radicals were found to be (8.1±1.2)·105M–1·s–1 for spontaneous disproportionation, (9.8±1.5)·106 M–1·s–1 in the presence of ceruloplasmin, and (2.1±0.3)·109M–1·s–1 in the presence of superoxide dismutase.
Non-alcoholic fatty liver disease is one of the most common chronic liver diseases with unclarified pathomechanism and without evidence-proven therapy. Dietary polyphenols, targeting oxidative stress, are at the center of investigations. Our aim was to examine the effects of a polyphenol rich extract on metal element homeostasis and transmethylation ability in non-alcoholic fatty liver model. A ten-day rat model was used (control group, hyperlipidemic group with fat-rich diet, hyperlipidemic group with fat-rich diet and polyphenol supplementation, N = 8 in each group). The hyperlipidemic diet increased the concentration of the majority of the elements with significantly higher contents of B, Co, Cu, Fe, Mg, Mn, Na, Ni, P, Se, Si, and Zn in the liver. Further elevation of Al, Pb, and Sn concentrations could be observed in polyphenol supplemented animals. The polyphenol supplement unexpectedly decreased the transmethylation ability of the liver (132.00 vs. 114.15 vs. 92.25 HCHO μg g−1) further. The results emphasize the possible role of altered metal and non-metal element concentrations and decreased transmethylation ability in the pathomechanism of fatty liver disease. Dietary supplementation with natural compounds may have undesirable effect as well, there is the necessity to improve the efficacy of polyphenol formulations because of their low oral bioavailability.