Influence of the glass packing on the contamination of pharmaceutical products by aluminium. Part II: amino acids for parenteral nutrition.

The presence of aluminium in amino acids parenteral nutrition solutions can be related to the affinity of the amino acids for aluminium present in glass containers used for storage. For this study solutions of 19 amino acids used in parenteral nutrition were stored individually in glass flasks and the aluminium measured at determined time intervals. Solutions of complexing agents for aluminium, as ethylene-diaminetetraacetic acid, nitrilotriacetic acid, citrate, oxalate and fluoride ions were also stored in the same flasks and the aluminium measured during the same time interval. The measurements were made by electrothermal atomic absorption spectrometry. The aluminium content of the glass containers was also measured. The results showed that the glasses have from 0.6% to 0.8% Al. Only solutions of cysteine, cystine, aspartic acid and glutamic acid became contaminated by aluminium. As the same occurred with the complexing agents, aluminum can be released from glass due to an affinity of the substances for aluminium. Comparing the action of complexing agents and amino acids for which the stability constants of aluminium complex are known, it is possible to relate the magnitude of the stability constant with the aluminium leached from glass, the higher the stability constant, the higher the aluminium released. The analysis of commercial formulations with and without cysteine, cystine, glutamic acid or aspartic acid stored in glass containers confirms that the presence of these amino acids combined with the age of the soLution are, at least partially, responsible for the aluminium contamination. The resuLts demonstrated that the contamination is an ongoing process due to the presence of aluminium in glass combined with the affinity of some amino acids for this element.

Synthesis of novel 6-alpha and 6-beta-alkylcarbonylmethyl substituted penems.

6-alpha and 6-beta Alkylcarbonylmethyl penems were synthesized from 6-alpha-bromo and 6-oxo penicillanates respectively and their in vitro antibacterial activity was studied. The compounds were generally active against Gram-positive but not against Gram-negative strains, the compounds of the 6-beta series being more active. Relatively to imipenem, taken as reference compound, the penems resulted more stable towards chemical hydrolysis in Tris-HCl buffered medium (pH 7.4) but more sensitive towards dehydropeptidase-I (DHP-I).

Synthesis and antimicrobial activity of DNA-gyrase inhibiting derivatives of 4-oxo-1,4-dihydro-3-pyridinecarboxylic acid.

A series of 6-substituted-1-aryl-4-oxo-1,4-dihydronicotinic acids were synthesised as monocyclic analogues of the quinolones. The 6-(2-aryl-1-methylethenyl)- and of the 6-(2-arylethenyl)-substituted compounds were shown to possess antibacterial properties that correlate with DNA gyrase inhibitory activity. Differently from the quinolones the antimicrobial activity of the compounds of this study is predominantly against Gram positive strains. The structure-activity relationships ascertained for these monocyclic compounds differ from those established for the quinolones.