Physiochemical Properties and Kinetics ofthe Decomposition of N-Hydroxymethylated Ethionamide in Aqueous Solution and Assissment of its Solubility as Possible Pro-Drug

Abstract

The physiochemical properties and Kinetics of the decomposition of N-hydroxymethyl ethionamide in aqueous solution was studied to assess its suitability as pro-drug of ethionamide. The N-hydroxymethyl derivative was found to possess higher water solubility and higher intrinsic dissolution rate than the parent compound. The derivative also exhibited lower lipophilicity than the parent compound. and showed an apparent hydroxide ion catalysed decomposition in the pH range ofS - 8.8. The N-hydroxymethyl ethionamide was very rapidly cleaved to formaldehyde and the parent compound at pH 7.4 and 37°C and it is therefore suggested that N-hydroxymethylation may be considered as a potential means of obtaining pro-drug of ethionamide.