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E Albers

Publications and source records attributed to E Albers.

5 recordsLinked to original sources

Influence of the nitrogen source on Saccharomyces cerevisiae anaerobic growth and product formation.

To prevent the loss of raw material in ethanol production by anaerobic yeast cultures, glycerol formation has to be reduced. In theory, this may be done by providing the yeast with amino acids, since the de novo cell synthesis of amino acids from glucose and ammonia gives rise to a surplus of NADH, which has to be reoxidized by the formation of glycerol. An industrial strain of Saccharomyces cerevisiae was cultivated in batch cultures with different nitrogen sources, i.e., ammonium salt, glutamic acid, and a mixture of amino acids, with 20 g of glucose per liter as the carbon and energy source. The effects of the nitrogen source on metabolite formation, growth, and cell composition were measured. The glycerol yields obtained with glutamic acid (0.17 mol/mol of glucose) or with the mixture of amino acids (0.10 mol/mol) as a nitrogen source were clearly lower than those for ammonium-grown cultures (0.21 mol/mol). In addition, the ethanol yield increased for growth on both glutamic acid (by 9%) and the mixture of amino acids (by 14%). Glutamic acid has a large influence on the formation of products; the production of, for example, alpha-ketoglutaric acid, succinic acid, and acetic acid, increased compared with their production with the other nitrogen sources. Cultures grown on amino acids have a higher specific growth rate (0.52 h-1) than cultures of both ammonium-grown (0.45 h-1) and glutamic acid-grown (0.33 h-1) cells. Although the product yields differed, similar compositions of the cells were attained. The NADH produced in the amino acid, RNA, and extracellular metabolite syntheses was calculated together with the corresponding glycerol formation. The lower-range values of the theoretically calculated yields of glycerol were in good agreement with the experimental yields, which may indicate that the regulation of metabolism succeeds in the most efficient balancing of the redox potential.

Amino Acids↗

Cyclodextrin derivatives in pharmaceutics.

The current cyclodextrin (CD) literature is reviewed concerning synthesis, characterization, and pharmaceutical relevant applications of CD derivatives. Although natural CDs have been used extensively to improve pharmaceutical properties, the effects of chemically modified CDs on the solubility, dissolution rate, and stability of drugs are overproportional. Concerning the parenteral application, the major interest is focussed on highly water-soluble, randomly substituted hydroxyalkyl derivatives of beta- and gamma-CD such as 2-hydroxypropyl-beta-cyclodextrin (2-HP-beta-CD). Although the heptakis-(2,6-di-O-methyl)-beta-cyclodextrin is applied in the pharmaceutical field, 2-HP-beta-CD is predestined as a parenteral drug carrier owing to its weak hemolytic activity and intrinsically amorphous character. A minimal average degree of substitution is especially preferred when 2-HP-beta-CD is used as solubilizer of pharmaceuticals for the use in parenteral applications. The influence of the type, degree, and pattern of substitution of the CDs, as well as substituent effects of the guest molecule is elucidated.

2-Hydroxypropyl-beta-cyclodextrin↗

Complexation of steroid hormones with cyclodextrin derivatives: substituent effects of the guest molecule on solubility and stability in aqueous solution.

The inclusion complexation of homologous derivatives of steroid hormones with cyclodextrins and 2-hydroxypropyl-beta-cyclodextrin (2-HP-beta-CD) was investigated with regard to underlying structure-interaction relationship. The interaction was studied by phase solubility analysis and stabilization effects of complex formation with 2-HP-beta-CD. The solubilizing and stabilizing abilities of 2-HP-beta-CD were generally more effective for testosterone derivatives than for estradiol esters. Within a homologous series of steroid hormones, the steepest linear solubility isotherms were found for 17-methyl and 3-methyl derivatives. The solubilization of steroid esters by 2-HP-beta-CD depended on the structure and length of the ester side chain. The interaction of 2-HP-beta-CD with the steroids was hindered by long-chain fatty acid ester groups. With increasing length of the side chain, a decline of the isotherms occurred and the phase solubility behavior changed from linear to exponential. Contrary to expectations, benzoylation of steroids considerably decreased the guest-host interaction. The observed rates of degradation of the steroid esters were significantly reduced by 2-HP-beta-CD, depending on the chain length, and correlated well with the order found in phase solubility analysis. The degradation showed no deviations from pseudo-first-order kinetics, and the degradation mechanism was not changed because of complexation. The results suggest that interaction of 2-HP-beta-CD with steroid esters involves the ester functions of the prodrugs and is more suitable for unsubstituted guest molecules.

2-Hydroxypropyl-beta-cyclodextrin↗

Effect of hydrotropic substances on the complexation of sparingly soluble drugs with cyclodextrin derivatives and the influence of cyclodextrin complexation on the pharmacokinetics of the drugs.

The influence of hydrotropic compounds on complex formation by 2-hydroxypropyl-beta-cyclodextrin (2-HP-beta-CD) was investigated with methyltestosterone (MeT). Various representatives of the lyotropic series were used for this purpose. Additive hydrotropic effects were observed for nicotinamide and urea, which disrupt the water structure, while structure formers such as sorbitol exerted negative effects. The effects of hydrotropic substances on the phase solubility relationship of MeT showed that inclusion complex formation with 2-HP-beta-CD depends on the degree of ordering of the solvent and is apparently subject to entropy effects. Combined systems comprising 2-HP-beta-CD and auxiliary substances with various underlying solubilizing principles were also investigated. Combination of 2-HP-beta-CD with conventional solubilizers, such as 1,2-propylene glycol or sodium deoxycholate, reduced the solubilization capacity of 2-HP-beta-CD. Competitive displacement of the inclusion molecule from its 2-HP-beta-CD complex by sodium deoxycholate suggested that cholesterol participates in the release mechanism of the inclusion molecule under in vivo conditions. The spontaneous release of complexed drug molecules could indirectly be shown on the basis of the spontaneous action of a complexed dihydropyridine derivative after iv administration in rats. The bioavailability of an investigational drug in cynomolgus monkeys could be enhanced sevenfold by inclusion complexation with 2-HP-beta-CD.

2-Hydroxypropyl-beta-cyclodextrin↗