Antimicrobial and diffusional correlation of N-alkyl betaines and N-alkyl-N,N-dimethylamine oxides from semisolids.

Previous studies have shown that two classes of amphoteric surfactants, N-alkyl betaines and N-alkyl-N,N-dimethylamine oxides, exhibit pronounced antimicrobial activity in combination and have potential for use in a semisolid formulation for topical or vaginal delivery. In this work, several potential delivery systems were prepared and evaluated for antimicrobial activity and diffusional properties. A novel antimicrobial test for semisolids was proposed that determined the contact time needed to kill microorganisms. The unformulated agents in solution exhibited the faster kill within 60 min, followed by the hydroxyethylcellulose gel formulation in 90 min, and the poloxamer gel and a cream that required several hours. Diffusion from the dosage form utilized a Slide-A-Lyzer diffusion cassette with a 10,000 MWCO membrane with (14)C-labeled active species added to the aforementioned antimicrobial formulations. Diffusion of the individual betaine and amine oxide derivatives were tracked over time to determine the diffusion rates and profiles of the components in each formulation and in solution. The betaine derivative diffused up to three times faster than the amine oxide derivative within the first 2 h, but the amount diffused was approximately equivalent at 24 h. The formulations delayed release in the same rank order as the contact time kill analysis: hydroxyethylcellulose gel > poloxamer gel > cream.

Use of the Vibrio harveyi toxicity test for evaluating mixture interactions of nitrobenzene and dinitrobenzene.

A mixture toxicity investigation was conducted using the bioluminescent marine bacterium Vibrio harveyi as the test organism for dual combinations of nitrobenzene and dinitrobenzene. Change in bioluminescence was used for determination of toxicity. Combination toxicity was evaluated using statistical comparisons, isopleths (isobologram and isobole plot), an additive index, and a mixture toxicity index. Both isopleths and mixture toxicity indices suggest that various combinations are additive, while the additive index value suggests antagonism. All evaluations were conducted as equitoxic mixtures. Statistical determination was performed using the z test. Numerous comparisons were different at the 1% level. Slope of line associated with isobole plot was suggested to be an important factor, resulting in statistical differences among comparisons. Distribution, using the Shapiro-Wilk test, was determined for both individual combination groups and solution composition in isopleths. All distributions evaluated were normal. These results suggest that the V. harveyi toxicity test is useful for mixture toxicity studies.